6.4: Glossary- The Muscular System - Biology

6.4: Glossary- The Muscular System - Biology

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move away from midline in the sagittal plane
abductor digiti minimi
muscle that abducts the little finger
abductor pollicis brevis
muscle that abducts the thumb
abductor pollicis longus
muscle that inserts into the first metacarpal
moves the bone away from the midline
adductor brevis
muscle that adducts and medially rotates the thigh
adductor longus
muscle that adducts, medially rotates, and flexes the thigh
adductor magnus
muscle with an anterior fascicle that adducts, medially rotates and flexes the thigh, and a posterior fascicle that assists in thigh extension
adductor pollicis
muscle that adducts the thumb
moves the bone toward the midline
(also, prime mover) muscle whose contraction is responsible for producing a particular motion
anal triangle
posterior triangle of the perineum that includes the anus
small muscle on the lateral posterior elbow that extends the forearm
muscle that opposes the action of an agonist
anterior compartment of the arm
(anterior flexor compartment of the arm) the biceps brachii, brachialis, brachioradialis, and their associated blood vessels and nerves
anterior compartment of the forearm
(anterior flexor compartment of the forearm) deep and superficial muscles that originate on the humerus and insert into the hand
anterior compartment of the leg
region that includes muscles that dorsiflex the foot
anterior compartment of the thigh
region that includes muscles that flex the thigh and extend the leg
anterior scalene
a muscle anterior to the middle scalene
of the arms and legs
of the trunk and head
bulky central body of a muscle
biceps brachii
two-headed muscle that crosses the shoulder and elbow joints to flex the forearm while assisting in supinating it and flexing the arm at the shoulder
biceps femoris
hamstring muscle
pennate muscle that has fascicles that are located on both sides of the tendon
muscle deep to the biceps brachii that provides power in flexing the forearm.
muscle that can flex the forearm quickly or help lift a load slowly
muscle that compresses the cheek
calcaneal tendon
(also, Achilles tendon) strong tendon that inserts into the calcaneal bone of the ankle
caval opening
opening in the diaphragm that allows the inferior vena cava to pass through; foramen for the vena cava
(also, sphincter) fascicles that are concentrically arranged around an opening
compressor urethrae
deep perineal muscle in women
fascicles that extend over a broad area and converge on a common attachment site
muscle that flexes and adducts the arm
corrugator supercilii
prime mover of the eyebrows
deep anterior compartment
flexor pollicis longus, flexor digitorum profundus, and their associated blood vessels and nerves
deep posterior compartment of the forearm
(deep posterior extensor compartment of the forearm) the abductor pollicis longus, extensor pollicis brevis, extensor pollicis longus, extensor indicis, and their associated blood vessels and nerves
deep transverse perineal
deep perineal muscle in men
shoulder muscle that abducts the arm as well as flexes and medially rotates it, and extends and laterally rotates it
skeletal muscle that separates the thoracic and abdominal cavities and is dome-shaped at rest
muscle that has anterior and posterior bellies and elevates the hyoid bone and larynx when one swallows; it also depresses the mandible
dorsal group
region that includes the extensor digitorum brevis
dorsal interossei
muscles that abduct and flex the three middle fingers at the metacarpophalangeal joints and extend them at the interphalangeal joints
epicranial aponeurosis
(also, galea aponeurosis) flat broad tendon that connects the frontalis and occipitalis
erector spinae group
large muscle mass of the back; primary extensor of the vertebral column
extensor carpi radialis brevis
muscle that extends and abducts the hand at the wrist
extensor carpi ulnaris
muscle that extends and adducts the hand
extensor digiti minimi
muscle that extends the little finger
extensor digitorum brevis
muscle that extends the toes
extensor digitorum longus
muscle that is lateral to the tibialis anterior
extensor digitorum
muscle that extends the hand at the wrist and the phalanges
extensor hallucis longus
muscle that is partly deep to the tibialis anterior and extensor digitorum longus
extensor indicis
muscle that inserts onto the tendon of the extensor digitorum of the index finger
extensor pollicis brevis
muscle that inserts onto the base of the proximal phalanx of the thumb
extensor pollicis longus
muscle that inserts onto the base of the distal phalanx of the thumb
extensor radialis longus
muscle that extends and abducts the hand at the wrist
extensor retinaculum
band of connective tissue that extends over the dorsal surface of the hand
muscle that increases the angle at the joint
external intercostal
superficial intercostal muscles that raise the rib cage
external oblique
superficial abdominal muscle with fascicles that extend inferiorly and medially
extrinsic eye muscles
originate outside the eye and insert onto the outer surface of the white of the eye, and create eyeball movement
extrinsic muscles of the hand
muscles that move the wrists, hands, and fingers and originate on the arm
muscle fibers bundled by perimysium into a unit
femoral triangle
region formed at the junction between the hip and the leg and includes the pectineus, femoral nerve, femoral artery, femoral vein, and deep inguinal lymph nodes
fibularis brevis
(also, peroneus brevis) muscle that plantar flexes the foot at the ankle and everts it at the intertarsal joints
fibularis longus
(also, peroneus longus) muscle that plantar flexes the foot at the ankle and everts it at the intertarsal joints
fibularis tertius
small muscle that is associated with the extensor digitorum longus
synergist that assists an agonist by preventing or reducing movement at another joint, thereby stabilizing the origin of the agonist
movement that decreases the angle of a joint
flexor carpi radialis
muscle that flexes and abducts the hand at the wrist
flexor carpi ulnaris
muscle that flexes and adducts the hand at the wrist
flexor digiti minimi brevis
muscle that flexes the little finger
flexor digitorum longus
muscle that flexes the four small toes
flexor digitorum profundus
muscle that flexes the phalanges of the fingers and the hand at the wrist
flexor digitorum superficialis
muscle that flexes the hand and the digits
flexor hallucis longus
muscle that flexes the big toe
flexor pollicis brevis
muscle that flexes the thumb
flexor pollicis longus
muscle that flexes the distal phalanx of the thumb
flexor retinaculum
band of connective tissue that extends over the palmar surface of the hand
muscle that decreases the angle at the joint
front part of the occipitofrontalis muscle
muscle that has fascicles that are spindle-shaped to create large bellies
most superficial muscle of the calf
muscle that originates on the mandible and allows the tongue to move downward and forward
muscle that depresses the mandible, and raises and pulls the hyoid bone anteriorly
gluteal group
muscle group that extends, flexes, rotates, adducts, and abducts the femur
gluteus maximus
largest of the gluteus muscles that extends the femur
gluteus medius
muscle deep to the gluteus maximus that abducts the femur at the hip
gluteus minimus
smallest of the gluteal muscles and deep to the gluteus medius
muscle that adducts the thigh and flexes the leg at the knee
hamstring group
three long muscles on the back of the leg
muscle that originates on the hyoid bone to move the tongue downward and flatten it
hypothenar eminence
rounded contour of muscle at the base of the little finger
group of muscles on the medial aspect of the palm
muscle that, along with the psoas major, makes up the iliopsoas
muscle that makes up the levator ani along with the pubococcygeus
iliocostalis cervicis
muscle of the iliocostalis group associated with the cervical region
iliocostalis group
laterally placed muscles of the erector spinae
iliocostalis lumborum
muscle of the iliocostalis group associated with the lumbar region
iliocostalis thoracis
muscle of the iliocostalis group associated with the thoracic region
iliopsoas group
muscle group consisting of iliacus and psoas major muscles, that flexes the thigh at the hip, rotates it laterally, and flexes the trunk of the body onto the hip
iliotibial tract
muscle that inserts onto the tibia; made up of the gluteus maximus and connective tissues of the tensor fasciae latae
inferior extensor retinaculum
cruciate ligament of the ankle
inferior gemellus
muscle deep to the gluteus maximus on the lateral surface of the thigh that laterally rotates the femur at the hip
infrahyoid muscles
anterior neck muscles that are attached to, and inferior to the hyoid bone
muscle that laterally rotates the arm
innermost intercostal
the deepest intercostal muscles that draw the ribs together
end of a skeletal muscle that is attached to the structure (usually a bone) that is moved when the muscle contracts
intercostal muscles
muscles that span the spaces between the ribs
group of midpalmar muscles
internal intercostal
muscles the intermediate intercostal muscles that draw the ribs together
internal oblique
flat, intermediate abdominal muscle with fascicles that run perpendicular to those of the external oblique
intrinsic muscles of the hand
muscles that move the wrists, hands, and fingers and originate in the palm
muscle that assists the levator ani and pulls the coccyx anteriorly
lateral compartment of the leg
region that includes the fibularis (peroneus) longus and the fibularis (peroneus) brevis and their associated blood vessels and nerves
lateral pterygoid
muscle that moves the mandible from side to side
to the outside
latissimus dorsi
broad, triangular axial muscle located on the inferior part of the back
levator ani
pelvic muscle that resists intra-abdominal pressure and supports the pelvic viscera
linea alba
white, fibrous band that runs along the midline of the trunk
longissimus capitis
muscle of the longissimus group associated with the head region
longissimus cervicis
muscle of the longissimus group associated with the cervical region
longissimus group
intermediately placed muscles of the erector spinae
longissimus thoracis
muscle of the longissimus group associated with the thoracic region
muscle that flexes each finger at the metacarpophalangeal joints and extend each finger at the interphalangeal joints
main muscle for chewing that elevates the mandible to close the mouth
medial compartment of the thigh
a region that includes the adductor longus, adductor brevis, adductor magnus, pectineus, gracilis, and their associated blood vessels and nerves
medial pterygoid
muscle that moves the mandible from side to side
to the inside
middle scalene
longest scalene muscle, located between the anterior and posterior scalenes
muscle of the lumbar region that helps extend and laterally flex the vertebral column
pennate muscle that has a tendon branching within it
muscle that lifts the hyoid bone and helps press the tongue to the top of the mouth
at an angle
obturator externus
muscle deep to the gluteus maximus on the lateral surface of the thigh that laterally rotates the femur at the hip
obturator internus
muscle deep to the gluteus maximus on the lateral surface of the thigh that laterally rotates the femur at the hip
posterior part of the occipitofrontalis muscle
muscle that makes up the scalp with a frontal belly and an occipital belly
muscle that has superior and inferior bellies and depresses the hyoid bone
opponens digiti minimi
muscle that brings the little finger across the palm to meet the thumb
opponens pollicis
muscle that moves the thumb across the palm to meet another finger
orbicularis oculi
circular muscle that closes the eye
orbicularis oris
circular muscle that moves the lips
end of a skeletal muscle that is attached to another structure (usually a bone) in a fixed position
muscle that originates on the soft palate to elevate the back of the tongue
palmar interossei
muscles that abduct and flex each finger at the metacarpophalangeal joints and extend each finger at the interphalangeal joints
palmaris longus
muscle that provides weak flexion of the hand at the wrist
fascicles that extend in the same direction as the long axis of the muscle
patellar ligament
extension of the quadriceps tendon below the patella
muscle that abducts and flexes the femur at the hip
pectoral girdle
shoulder girdle, made up of the clavicle and scapula
pectoralis major
thick, fan-shaped axial muscle that covers much of the superior thorax
pectoralis minor
muscle that moves the scapula and assists in inhalation
pelvic diaphragm
muscular sheet that comprises the levator ani and the ischiococcygeus
pelvic girdle
hips, a foundation for the lower limb
fascicles that are arranged differently based on their angles to the tendon
diamond-shaped region between the pubic symphysis, coccyx, and ischial tuberosities
muscle deep to the gluteus maximus on the lateral surface of the thigh that laterally rotates the femur at the hip
plantar aponeurosis
muscle that supports the longitudinal arch of the foot
plantar group
four-layered group of intrinsic foot muscles
muscle that runs obliquely between the gastrocnemius and the soleus
popliteal fossa
diamond-shaped space at the back of the knee
muscle that flexes the leg at the knee and creates the floor of the popliteal fossa
posterior compartment of the leg
region that includes the superficial gastrocnemius, soleus, and plantaris, and the deep popliteus, flexor digitorum longus, flexor hallucis longus, and tibialis posterior
posterior compartment of the thigh
region that includes muscles that flex the leg and extend the thigh
posterior scalene
smallest scalene muscle, located posterior to the middle scalene
prime mover
(also, agonist) principle muscle involved in an action
pronator quadratus
pronator that originates on the ulna and inserts on the radius
pronator teres
pronator that originates on the humerus and inserts on the radius
psoas major
muscle that, along with the iliacus, makes up the iliopsoas
muscle that makes up the levator ani along with the iliococcygeus
quadratus femoris
muscle deep to the gluteus maximus on the lateral surface of the thigh that laterally rotates the femur at the hip
quadratus lumborum
posterior part of the abdominal wall that helps with posture and stabilization of the body
quadriceps femoris group
four muscles, that extend and stabilize the knee
quadriceps tendon
(also, patellar tendon) tendon common to all four quadriceps muscles, inserts into the patella
rectus abdominis
long, linear muscle that extends along the middle of the trunk
rectus femoris
quadricep muscle on the anterior aspect of the thigh
rectus sheaths
tissue that makes up the linea alba
fibrous bands that sheath the tendons at the wrist
rhomboid major
muscle that attaches the vertebral border of the scapula to the spinous process of the thoracic vertebrae
rhomboid minor
muscle that attaches the vertebral border of the scapula to the spinous process of the thoracic vertebrae
rotator cuff
(also, musculotendinous cuff) the circle of tendons around the shoulder joint
band-like muscle that flexes, abducts, and laterally rotates the leg at the hip
scalene muscles
flex, laterally flex, and rotate the head; contribute to deep inhalation
segmental muscle group
interspinales and intertransversarii muscles that bring together the spinous and transverse processes of each consecutive vertebra
hamstring muscle
semispinalis capitis
transversospinales muscle associated with the head region
semispinalis cervicis
transversospinales muscle associated with the cervical region
semispinalis thoracis
transversospinales muscle associated with the thoracic region
hamstring muscle
serratus anterior
large and flat muscle that originates on the ribs and inserts onto the scapula
wide, flat muscle deep to the gastrocnemius
sphincter urethrovaginalis
deep perineal muscle in women
spinalis capitis
muscle of the spinalis group associated with the head region
spinalis cervicis
muscle of the spinalis group associated with the cervical region
spinalis group
medially placed muscles of the erector spinae
spinalis thoracis
muscle of the spinalis group associated with the thoracic region
splenius capitis
neck muscle that inserts into the head region
splenius cervicis
neck muscle that inserts into the cervical region
posterior neck muscles; includes the splenius capitis and splenius cervicis
major muscle that laterally flexes and rotates the head
muscle that depresses the hyoid bone
muscle that depresses the larynx’s thyroid cartilage
muscle that originates on the styloid bone, and allows upward and backward motion of the tongue
muscle that elevates the hyoid bone posteriorly
muscle that stabilizes the clavicle during movement
muscle that originates on the anterior scapula and medially rotates the arm
superficial anterior compartment of the forearm
flexor carpi radialis, palmaris longus, flexor carpi ulnaris, flexor digitorum superficialis, and their associated blood vessels and nerves
superficial posterior compartment of the forearm
extensor radialis longus, extensor carpi radialis brevis, extensor digitorum, extensor digiti minimi, extensor carpi ulnaris, and their associated blood vessels and nerves
superior extensor retinaculum
transverse ligament of the ankle
superior gemellus
muscle deep to the gluteus maximus on the lateral surface of the thigh that laterally rotates the femur at the hip
muscle that moves the palm and forearm anteriorly
suprahyoid muscles
neck muscles that are superior to the hyoid bone
muscle that abducts the arm
muscle whose contraction helps a prime mover in an action
muscle that retracts the mandible
tendinous intersections
three transverse bands of collagen fibers that divide the rectus abdominis into segments
tensor fascia lata
muscle that flexes and abducts the thigh
teres major
muscle that extends the arm and assists in adduction and medial rotation of it
teres minor
muscle that laterally rotates and extends the arm
thenar eminence
rounded contour of muscle at the base of the thumb
group of muscles on the lateral aspect of the palm
muscle that depresses the hyoid bone and elevates the larynx’s thyroid cartilage
tibialis anterior
muscle located on the lateral surface of the tibia
tibialis posterior
muscle that plantar flexes and inverts the foot
muscles that originate at the transverse processes and insert at the spinous processes of the vertebrae
transversus abdominis
deep layer of the abdomen that has fascicles arranged transversely around the abdomen
muscle that stabilizes the upper part of the back
triceps brachii
three-headed muscle that extends the forearm
pennate muscle that has fascicles located on one side of the tendon
urogenital triangle
anterior triangle of the perineum that includes the external genitals
vastus intermedius
quadricep muscle that is between the vastus lateralis and vastus medialis and is deep to the rectus femoris
vastus lateralis
quadricep muscle on the lateral aspect of the thigh
vastus medialis
quadricep muscle on the medial aspect of the thigh

Musculoskeletal System

The muscular and skeletal systems provide support to the body and allow for movement. The bones of the skeleton protect the body’s internal organs and support the weight of the body. The muscles of the muscular system contract and pull on the bones, allowing for movements as diverse as standing, walking, running, and grasping items.

Injury or disease affecting the musculoskeletal system can be very debilitating. The most common musculoskeletal diseases worldwide are caused by malnutrition, which can negatively affect development and maintenance of bones and muscles. Other diseases affect the joints, such as arthritis, which can make movement difficult and, in advanced cases, completely impair mobility.

Progress in the science of prosthesis design has resulted in the development of artificial joints, with joint replacement surgery in the hips and knees being the most common. Replacement joints for shoulders, elbows, and fingers are also available.

Examples of Organ Systems

The human organ systems are:

  • Integumentary
  • Skeletal
  • Muscular
  • Circulatory
  • Respiratory
  • Digestive
  • Urinary
  • Immune
  • Nervous
  • Endocrine
  • Reproductive

The Integumentary System

The integumentary system consists of external organs that protect the body from damage, including the skin, fingernails, and hair. Skin is the largest organ of the human body. It is made up of three layers: the epidermis, dermis, and hypodermis, which contains stored body fat. Nails and hair are both made up of the protein keratin. In other animals, the integumentary system may include feathers, scales, or hooves.

Besides protecting the internal organs from physical damage, the integumentary system has multiple other functions such as protecting against virus invasion, dehydration, sunburns, and changes in temperature, making Vitamin D through sun exposure, and excreting waste through sweating.

The Skeletal System

The skeletal system is made up of all the bones in the human body, i.e., the skeleton. The skeleton forms the supporting structure of the body. It comes from the Greek σκελετός (skeletós), meaning “dried up”, referring to the dry nature of bones. A human infant has 270 bones, some of which fuse together to form the 206 bones in the adult human body. Cartilage is the precursor to bone when an embryo is developing, and it is found in some structures in the human body such as the nose, ears, and joints.
An internal support structure in an animal is called an endoskeleton. Some animals such as insects have hard coverings called exoskeletons on the outside instead of inside the body.

The Muscular System

The muscular system includes the different types of muscles in the body: cardiac, smooth, and skeletal muscles. Cardiac muscles are found only in the heart and contract to pump blood. Smooth muscles are found in organs such as the stomach, intestines, and bladder and move without conscious effort by the organism. Skeletal muscles are attached to bones and work together with bones to move the body.

The Circulatory System

Humans and other vertebrates have closed circulatory systems, where the blood is enclosed within blood vessels like veins and arteries. Some animals, such as insects, have open circulatory systems, where blood is pumped into body cavities without the use of vessels.

The Respiratory System

The respiratory system is made up of the organs used for breathing, including the lungs, diaphragm, trachea, bronchi, and bronchioles. In the lungs, oxygen and carbon dioxide are exchanged between the outside air and the blood. Other animals breathe through gills or even through their skin.

The Digestive System

The digestive system digests food and absorbs it into the body. It is made up of the gastrointestinal tract (which includes the esophagus, stomach, liver, and intestines) along with accessory organs of digestion. These include the tongue, liver, pancreas, and gallbladder.

The Urinary System

The urinary system gets rid of wastes from the body in the form of urine. The kidneys, ureters, bladder, and urethra are all part of the urinary system. Sometimes the organs of the urinary system are grouped together with organs that remove wastes such as the skin, lungs, and large intestine, and this is called the excretory system.

The Immune System

The immune system is an organism’s defense system it protects against disease. Important parts of the immune system include leukocytes (white blood cells), bone marrow, and the thymus. There are many different types of white blood cells, like helper T cells, killer T cells, and B cells. The lymphatic system is also associated with the immune system.

The Nervous System

The nervous system sends and interprets signals from different parts of the body and organizes the body’s actions. The central nervous system includes the brain and spinal cord, while the peripheral nervous system is made up of nerves that allow the central nervous system to connect to the rest of the body.

The Endocrine System

The endocrine system is comprised of all the glands in the body that produce hormones, which are carried via the bloodstream to affect other organs. Some important glands are the pituitary gland, which produces reproductive and many other body-regulating hormones the thyroid, which has roles in metabolism and protein synthesis and the adrenal glands, which produce adrenaline and stimulate the fight-or-flight response.

The Reproductive System

The reproductive system includes an organism’s sex organs. In females, some of the sex organs are the vagina, uterus, and ovaries. In males, some sex organs are the penis, testes, prostrate, and vas deferens. All of these organs play a role in sexual reproduction.

The neck

The motion of the neck is described in terms of rotation, flexion, extension, and side bending (i.e., the motion used to touch the ear to the shoulder). The direction of the action can be ipsilateral, which refers to movement in the direction of the contracting muscle, or contralateral, which refers to movement away from the side of the contracting muscle.

Rotation is one of the most-important actions of the cervical (neck) spine. Rotation is accomplished primarily by the sternocleidomastoid muscle, which bends the neck to the ipsilateral side and rotates the neck contralaterally. Together, the sternocleidomastoid muscles on both sides of the neck act to flex the neck and raise the sternum to assist in forced inhalation. The anterior and middle scalene muscles, which also are located at the sides of the neck, act ipsilaterally to rotate the neck, as well as to elevate the first rib. The splenius capitis and splenius cervicis, which are located in the back of the neck, work to rotate the head.

Side bending also is an important action of the cervical spine. The sternocleidomastoid muscles are involved in cervical side bending. The posterior scalene muscles, located on the lower sides of the neck, ipsilaterally bend the neck to the side and elevate the second rib. The splenius capitis and splenius cervicis also assist in neck side bending. The erector spinae muscles (iliocostalis, longissimus, and spinalis) are large, deep muscles that extend the length of the back. All three act to ipsilaterally side bend the neck.

Neck flexion refers to the motion used to touch the chin to the chest. It is accomplished primarily by the sternocleidomastoid muscles, with assistance from the longus colli and the longus capitis, which are found in the front of the neck. Neck extension is the opposite of flexion and is accomplished by many of the same muscles that are used for other neck movements, including the splenius cervicis, splenius capitis, iliocostalis, longissimus, and spinalis muscles.

Muscle Satellite Cells: Exploring the Basic Biology to Rule Them

Adult skeletal muscle is a postmitotic tissue with an enormous capacity to regenerate upon injury. This is accomplished by resident stem cells, named satellite cells, which were identified more than 50 years ago. Since their discovery, many researchers have been concentrating efforts to answer questions about their origin and role in muscle development, the way they contribute to muscle regeneration, and their potential to cell-based therapies. Satellite cells are maintained in a quiescent state and upon requirement are activated, proliferating, and fusing with other cells to form or repair myofibers. In addition, they are able to self-renew and replenish the stem pool. Every phase of satellite cell activity is highly regulated and orchestrated by many molecules and signaling pathways the elucidation of players and mechanisms involved in satellite cell biology is of extreme importance, being the first step to expose the crucial points that could be modulated to extract the optimal response from these cells in therapeutic strategies. Here, we review the basic aspects about satellite cells biology and briefly discuss recent findings about therapeutic attempts, trying to raise questions about how basic biology could provide a solid scaffold to more successful use of these cells in clinics.

1. Introduction

Skeletal muscle is a postmitotic tissue that has a high regenerative potential. This feature is mainly due to satellite cells (SCs), which form a reservoir of precursor cells that are responsible for its after-birth growth and also for the response to injuries, either by exercise or by disease [1]. Their amounts in the adult muscle could vary between 3 and 11% of the myonuclei, depending upon which species are being analyzed. In mice, the amount of SCs drops from 32% in neonates to 5% in adults [2, 3]. These cells are strictly associated with the sarcolemma, residing between the membrane and the basal lamina [4], becoming associated with the muscle fiber before the formation of its surrounding lamina [3].

These cells are easily identified by their location and morphology. However, efficient ways to obtain these cells involve the use of several markers that characterize this cell type, the transcription factor Pax7 being the most remarkable one [5]. Even though they are well studied and recognized, the SC population is highly heterogeneous [6].

Although quiescent in normal adult muscles, these cells can be activated by specific signals when a muscle injury occurs. Upon activation these cells undergo asymmetric division, by which they could form cells that either are capable of self-renewing or can enter the myogenic pathway and differentiate to restore the muscle [7–9]. Nonetheless, in diseases characterized by relentless degeneration, like muscular dystrophies, the satellite cells are constantly activated, which eventually leads to depletion of the SC pool and consequent failure of the regeneration process [10]. Currently, there is no effective treatment for muscle degenerative diseases thus, many researchers are focusing on stem cell-based therapies. However, to date, most attempts are limited to animal models and former clinical trials have failed.

In this review, we summarize recent findings about the basic biology of muscle-specific stem cells and discuss possible new avenues to more effective and feasible therapeutic approaches to muscle wasting disorders, mainly muscular dystrophies.

2. Origin of Satellite Cells in the Muscle Development

In the embryo, mesoderm structures called somites are formed and skeletal muscles are derived from a specific region, the dermomyotome [11]. In this step the first muscle fibers are formed and additional fibers are added afterwards using the former as a template [12, 13]. In the final period of embryogenesis, muscle progenitors start to proliferate vastly until they arrive in a state in which the number of nuclei is maintained and the synthesis of myofibrillar protein hits its peak [14]. The muscle then reaches a mature state with its residing progenitor cells, the SCs, acquiring a quiescent state in this tissue [11].

In somites, the high concentrations of FGF and Wnt in the caudal area lead to formation of mesenchymal cells in an undifferentiated state and this pathway also involves the control by Notch [15]. Then, the most dorsal part forms the dermomyotome, which will give rise to the majority of skeletal muscles. Cells of this compartment have high expression of the factors Pax3 and Pax7 and a low expression of the myogenic regulator Myf5 [16–18]. Afterwards, the maturation of a dermomyotome piece will form the myotome, which is characterized by the expression of MyoD and Myf5 [18–20]. Muscle progenitors subsequently intercalate into the primary myotome, and these will originate a fraction of the SCs that resides within the postnatal skeletal muscle [21–24].

SCs are known to participate in adult muscle regeneration, and many similarities have been described between this process and the embryonic myogenesis, as relating SCs to progenitors of somatic origin [21–23, 25] (Figure 1(a)). It is also important to notice that the cells involved in the adult regeneration process are under the same genetic hierarchy involved in embryonic myogenesis, with the same genes participating in their regulation [26] (Figure 1(b)). The major distinction between myogenesis in the embryo and regeneration is that the latter requires a scaffolding that will work as a template [27].

A number of data also indicate that there are specific SCs that undergo asymmetric division, generating committed cells dedicated to the regeneration process, but also producing new SCs that are able to replenish the muscle stem cells pool [11].

Adult myogenic cells are derived mainly from SCs during late fetal development. However, there has been evidence of other adult stem cell populations that can also be involved in regeneration [12]. Nonetheless, it is remarkable that even though these other stem cells exist and have myogenic potential, experiments that deplete Pax7-satellite cells show that no other stem cell type is able to replenish the SC pool nor act in regeneration after injury, highlighting the unique importance of SCs [28].

3. Satellite Cell Markers

Satellite cells can be identified by the expression of several markers, with special attention to Pax7, which is considered the main defining factor for this cell type [5]. This marker has been correlated with the maintenance of an undifferentiated state, being an important factor for self-renewal in these cells [29]. In addition to Pax7, another protein from the paired domain transcription factor family might be expressed, Pax3, which is also important in the initial steps of muscle formation and is involved in the transcription of another marker, the tyrosine receptor kinase c-Met [30–32]. Interestingly, in the knockout mouse for Pax7, some SCs can be found, indicating that Pax3 alone could play a similar role [30, 33]. Conversely, other results suggest that Pax3 is not able to compensate for the Pax7 function [32]. In addition, the presence of Pax3 SCs is dependent on the muscle type [30].

Besides the Pax protein family, many other markers can be used to identify SCs such as the myogenic regulatory factor Myf5 [31, 34] homeobox transcription factor Barx2, which is coexpressed with Pax7 and is a regulator of muscle growth, maintenance, and regeneration [35] cell adhesion protein M-cadherin, which is known to be coexpressed with c-Met [31, 36] cell surface attachment receptor 7-integrin [37, 38] cluster of differentiation protein (CD34) that is expressed in quiescent SCs [34] transmembrane heparan sulfate proteoglycans syndecan-3 and syndecan-4 [39] chemokine receptor CXCR4 [40] caveolae-forming protein caveolin-1 [38, 41] calcitonin receptor, which was described as related to the quiescent state [38, 42] vascular cell adhesion protein 1 VCAM-1 [43] neural cell adhesion molecule 1 NCAM-1 [44, 45] and nuclear envelop proteins lamin A/C and emerin [38]. However, these individual proteins are not exclusively expressed in SCs, meaning that only their simultaneous coexpression has been useful in identifying this cell type. Although other markers have been proposed to identify SCs, the ones cited above, and indicated in Figure 2, are the most commonly studied. Table 1 is presenting examples of antibodies for immunofluorescence referred to in the literature. Different antibodies can be used according to the adopted methodology (western blotting, flow cytometry, etc.).

4. Heterogeneity in the Satellite Cell Population

Even though the identification of satellite cells is based on marker expression and morphological analysis, it has been suggested that these cells comprise a heterogeneous population of precursor cells [33]. It has also been reported that these cells can be prone to be committed either to the muscle lineage or to the self-renewal pathway, which is also an evidence of its heterogeneity [44, 46, 47]. The expression of the markers cited in the previous section, although well established in the literature, can be variable in this cell population, being another indication that this cell population can be heterogeneous, even though cells maintain their myogenic potential.

For instance, the expression of the marker Myf5 has been reported to be absent in

10% of the SC population, and the cells identified as Pax7+/Myf5− contributed to their reservoir in contrast with Pax7+/Myf5+ cells that were committed to differentiation [48]. Studies also showed that activated cells expressing low levels of Pax7 were more committed to differentiation, whereas high levels of Pax7 were related to cells less prone to differentiate and that had more undifferentiated characteristics [49]. Experiments with histone 2B labeling also demonstrated that there are SCs that retain or lose this mark and that the former is able to self-renew and the cells that lose the mark are restricted to differentiation [50].

Differences were also observed in the proliferation rate of SCs, as slow and fast dividing cells coexist [51]. The slow ones are capable of long-term self-renewal, whereas fast dividing cells compromise themselves with the myogenic lineage without producing self-renewing progeny [52]. In this sense, subpopulations that are considered committed to the myogenic lineage could participate in the regeneration of an injured muscle before the ones that are still in the more progenitor state and so would take a longer time to be involved in this process [53]. This scenario is consistent with a stem cell to progenitor cell hierarchy.

As it is known that muscles within the body are distinct between themselves, it has been seen that SCs also present heterogeneity based on the muscle they are located within, which may correlate to their distinct embryonic origin [6, 54]. This is consistent with the previous results observed by Buckingham et al. and Relaix et al. that shows that the expression of Pax3 by SCs is muscle-dependent [30, 32]. As knowledge increased, studies were done to determine whether the heterogeneity of SCs in muscle was due to the muscle environment or internal programming, and the outcomes of distinct researches showed that there is evidence for both [55, 56].

Differences in SCs were also found when considering the extrafusal fibers and their categorization into fast and slow fibers regarding proliferation rate and differentiation potential. Remarkably, the SCs could differentiate into exclusive fast fibers when they came from a fast muscle and into fast or slow fibers when they are derived from a slow muscle [57–59]. As observed previously, the phenotype after differentiation can either be dependent on the intrinsic programming that is related to the fiber type or can be under influence of the environment, that is, the muscle fiber with whom the cell interacts [6, 60]. As for intrafusal fibers, SCs in this compartment are known to be more plastic and directed to a specific phenotype by foreign innervation stimulation [61, 62].

Morphological differences translated as round and thick cells were also observed in the SC population and they were associated with distinct myogenic potential [63], the thick ones being more prone to differentiation. Functionally, there are observations that suggest two subpopulations of SCs, one that is committed to muscle growth, whose cell number declines with age and is present in a larger amount in males, and another subpopulation related to muscle regeneration after an injury, whose cell amount is relatively maintained during aging and is not gender related [64].

The heterogeneity may also result from the distinct niche in which these cells are located, as has been observed in the aging process, where cells may escape quiescence and lose their capacity of self-renewal [65–67]. An important component of the muscle niche that acts directly in proliferation and differentiation of satellite cells is the fibro/adipogenic precursors, and it is known that they act positively in young Dmd mdx mice, the model for Duchenne Muscular Dystrophy, but repress the formation of myotubes in old ones, indicating that the process of aging has direct implications in satellite cells [68]. Other factors such as Notch and Wnt are also involved in this nonautonomous process of SCs aging [67, 69]. In addition, intrinsic changes in cells are also observed in the aging process, such as in geriatric SCs that lose the reversible quiescence and enter in a presenescence that cannot be reversed and that in an injured muscle fail to start the regenerative process and enter in a full senescence state [70]. It was also shown that intrinsic cell factors also lead to the loss of self-renewal with the involvement of the MAPK pathway [71, 72]. It is important to distinguish between autonomous and cell nonautonomous factors that interfere with SCs in aging, since the nonautonomous ones, such as the niche, can be corrected with a youthful environment [73], a fact that cannot be corrected when the factor is intrinsic to the cell [70].

This heterogeneity in the stem cell population in muscle has been complicating the identification, function, and naming of these cells. There has been in the literature a description of other types of cells with high myogenic capacity and directly related to muscle regeneration, called muscle derived stem cells that express distinct markers [74]. Nonetheless, it is important to notice that there have been subsequent results indicating that, without SCs, no other cell types have the capacity to regenerate muscle [28]. This may be either because the other cell types studied did not include the specific population described by Qu-Petersen and colleagues [74], or that the activity of other cell types has a requirement for use in conjunction with SCs or with the major SC factor Pax7 [75].

Additionally, diverse muscle derived stem cell (MDSC) populations had been identified. These populations include myogenic progenitor cells characterized as CD56+, CD34−, CD144−, CD45−, and CD146− CD56+, CD34+, CD144+, CD45−, and CD146− mio-endothelial cells CD56−, CD34−, CD144−, CD45−, and CD146+ perivascular progenitor cells and a muscle derived side population which has similar features to bone marrow stem cells [76]. Based on adhesion and proliferative properties, Qu-Petersen and colleagues [74] isolated three cell populations derived from muscle. Two of these populations, EP (early preplate) and LP (late preplate), represent the satellite cells the third one, which also adheres lately, is named MDSC and presents characteristics usually associated with noncommitted progenitor cells. The EP population represents the majority of the cells obtained from muscle digestion and differentiates into myotubes. However, EP cells have a limited regenerative potential. The LP population accounts for about 1% of satellite cells, but it has low rates of proliferation and differentiation. Conversely, MDSC showed a better self-renewal ability and sustained proliferation and are multipotent. Thus, the MDSC would be less committed cells and more promising for therapies in comparison to satellite cells [74].

Other cell types, such as bone marrow mesenchymal stem cells [77–81], adipose derived mesenchymal stem cells [82–84], CD133+ cells [85–87], pericytes/mesoangioblasts [88, 89], and side population cells [90, 91], were described as being able to participate in myotube formation as well as replenishing the satellite pool. These cells are not initially committed to muscle and may not express the classical satellite cell marker, Pax7. However, they are capable of contributing to muscle regeneration when fusing with myogenic cells and, additionally, they may be able to turn into Pax7 expressing cells originating new SCs, which is a fact that may strongly contribute to the heterogeneity observed in this population. It is also important to notice that evidence has been found that myogenic cells are formed by fusion [78, 92–94] or transdifferentiation, in which cells develop into intrinsically myogenic ones [95–97], and the heterogeneity would rise by the contribution of both cells that participate in the fusion process or by one cell initially not committed to muscle becoming myogenic. Furthermore, other cell types may be involved in assisting muscle regeneration sending signals that direct differentiation of SCs, such as fibro/adipogenic precursors [98–100]. It is clear then that whether one cell type turns into muscle by fusion or transdifferentiation or that the precursor itself receives signals that direct their proliferation and differentiation, the final outcome is that all these factors contribute to the myogenic population being heterogeneous.

5. Satellite Cells Can Undergo Multilineage Differentiation

Besides their myogenic potential, it has been described in the literature that these cells can undergo osteogenic and adipogenic differentiation, for example. This highlights their properties as a stem cell that is able to differentiate within the mesenchymal lineage [101–104].

Studies in rat showed that the heterogeneity in the proliferation rate correlates with the differentiation potential, with high proliferative clones being able to differentiate into adipocytes [105]. Morphological heterogeneity was also related to distinct potential, with thick cells also being able to undergo osteogenic differentiation [63]. Heterogeneity also in the CD34 expression was correlated with distinct potential to go through the adipogenic pathway, and only cells that expressed this marker were able to undergo adipogenic differentiation [106].

Additionally, in aged mice, it was observed that SCs tend to go to the fibrogenic lineage instead of maintaining their myogenic potential, which may contribute to the greater fibrosis observed in old mice [69].

6. The Balance between Quiescence and Activation

Skeletal muscle regeneration follows a series of steps that recapitulates the phases of development. First, muscle progenitor cells must exit the state of quiescence and become active and proliferate. Asymmetric divisions are important to provide daughter cells committed to the myogenic program (myoblasts) and also daughter cells that return to quiescent state in order to replenish the stem cell pool. After proliferation, myoblasts differentiate and fuse to form myotubes, which fuse with each other or to a previous fiber to repair it. Finally, the myofibers grow and maturate.

6.1. Quiescence Mechanisms

As other types of adult stem cells, SCs are quiescent until they are activated when there is a muscle injury. Maintenance of quiescence is crucial to preserve the SC pool and it is controlled by different molecular mechanisms, with participation of many genes and regulatory pathways. Microarray studies showed that more than 500 genes are overexpressed in quiescent SCs in comparison with proliferating myoblasts [42]. Negative regulators of cell cycle are among these genes. Despite the fact that all the players and mechanisms of SCs’ homeostasis are not being fully understood, many efforts have been employed in order to depict them (Figure 3).

The Notch signaling was implicated in SC quiescence maintenance, as well as proliferation and differentiation regulation, in various studies [107–111]. Indeed, Notch signaling was established as the first quiescence regulator in adult stem cells because an interruption in Notch activity favors spontaneous cell differentiation, without the entry in the S phase [110]. The highest activity of Notch signaling is seen in quiescent SCs and it is progressively reduced as the cell progresses through myogenic differentiation. Interestingly, Notch signaling prolonged blockage does not prevent cells from proliferating but leads to depletion of SC, demonstrating that it is necessary for self-renewal [110]. A similar study showed related results about the loss of Notch signaling by RBP-J deletion. The absence of Notch signaling has at least three main effects: failure of quiescence maintenance loss of the ability to self-renew and spontaneous differentiation, without a phase of proliferation [108].

The FOXO family of transcription factors regulates stem cell pools in adult tissues. The levels of Foxo3 transcript and protein are higher in quiescent SCs than in activated ones. The ablation of Foxo3 gene specifically in SCs showed that this transcription factor is important for SC return to quiescence and self-renew. FOXO3 negative cells are more proliferative and differentiate more rapidly, while Foxo3 overexpression suppresses cell cycle entry and represses terminal differentiation [112]. This work also links FOXO3 to Notch signaling: FOXO3 regulates NOTCH1 and NOTCH3 receptor expression, activating Notch signaling, and thus promotes quiescence in SCs [112].

MicroRNAs are significant players in gene expression regulation, including genes related to stem cell functions and their activity in SCs regulation has been recently explored. It was demonstrated that miR-489 is highly expressed in quiescent SCs and is downregulated as they become activated. A target of miR-489 is Dek, an oncogene, whose both mRNA and protein levels are higher in activated SCs than in quiescent SCs. In SCs, Dek promotes proliferation after activation Dek-positive cells are committed to myogenic differentiation and Dek-negative cells are self-renewing [113]. Another miRNA involved in SCs quiescence is miR-31. Although the majority of SCs in adult tissue have the Myf5 gene activated [48], they do not necessarily differentiate, which implies that a mechanism must exist to prevent Myf5 mRNA translation before the appropriated moment. This repression is accomplished by miR-31 that has a higher expression in quiescent SCs it targets Myf5 mRNA and then sequesters it in mRNP granules. Upon activation, miR-31 levels decrease and Myf5 mRNA is released to translation [114].

SCs quiescence is also established by mRNA decay. Hausburg and colleagues showed that Myod transcript is driven to mRNA decay, preventing the SC to proceed in the myogenic program. This is achieved by the action of the protein tristetraprolin (TTP) that binds to mRNA, preventing it to be translated and, in addition, regulating its decay [115].

All these posttranscriptional regulation mechanisms seem to be somewhat redundant and they seem to act in a subpopulation-specific manner however, more studies are necessary to clarify all the mechanisms involved in quiescence maintenance and to define whether they are common to all SCs.

6.2. Activation and Proliferation Mechanisms

When the muscle suffers an injury, the SCs must be activated, starting to proliferate and differentiate to repair and/or form new muscle fibers. SC activation is a transient process regulated at different levels. As Notch inhibits p38α/β MAPK signaling pathway in quiescent stage [116], this is the first pathway to be activated [117], resulting in the expression of Myod and consequent cell cycle entry. The damaged fibers release many growth factors that induce the activation of signaling pathways related to cell cycle, like TNF-α, HGF, and FGF [118–120]. The transition from G1 to S phase is achieved by activation of ERK1/2 pathway by Fgf2 [121]. Another MAPK signaling pathway involved in SC cell cycle progression is JNK [122].

The intense cell proliferation is important to muscle repair, but it has to be limited and the fate of each daughter cell must be determined—terminally differentiate or return to quiescence. Wnt/β-catenin signaling is temporally activated during regeneration but later downregulated to limit the regenerative response [123]. Wnt/β-catenin signaling is also involved in the promotion of myogenic differentiation. The treatment of SCs with Wnt3a promotes cell cycle arrest, myogenin activation, and follistatin expression, promoting myoblast fusion and terminal differentiation [124].

The JAK-STAT signaling is another player in the regulation of SC function, especially in the aged muscle, whereby Stat3 activation interferes in MyoD to promote myoblast differentiation [125]. JAK-STAT signaling increases progressively with age or disease. Jak2 and Stat3 transient inhibition in aged and dystrophic muscle enhances SC expansion and better muscle regeneration [126, 127].

6.3. Cell Cycle Exit

To exit the cell cycle, upregulation of inhibitors of cyclin-dependent kinases is required. The return to quiescence requires

, whereas the progression through myogenesis requires the upregulation of

, and p57 [50, 128, 129]. Sprouty1 (Spry1) is a receptor tyrosine kinase signaling inhibitor expressed in Pax7 + quiescent cells, but downregulated in proliferating myoblasts. When Pax7 + cells return to quiescence Spry1 is induced again, promoting cell cycle exit by inhibiting ERK pathway [130].

6.4. Asymmetric Divisions and Self-Renewal

The daughter cells asymmetry, that is, segregation of different determinant factors, will determine whether they differentiate or self-renew. The myogenic determinant factors Myf5, MyoD, and Myog have asymmetric expression in the daughter cells [48, 131, 132]. MyoD is distributed to committed Pax7− cells and the Pax+/MyoD− cells are self-renewing [133]. For Myog, the same is observed: the myogenic lineage is Pax7−/Myog+ and reservoir cells are Pax7+/Myog− [134]. The distribution of DNA template is also asymmetric: the old template goes to the daughter cell expressing Pax7, the reservoir cell, and the new DNA template to the one expressing Myog [134].

In Myf5-negative SCs, those compromised with renovation of the stem cell pool, the Notch3 receptor is enriched, whereas Myf5-positive cells receive the Notch ligand Delta1 [48] in Myog-positive cells there is also the presence of Numb, a Notch antagonist [107]. All these findings are related to the role of Notch signaling in maintenance of quiescence, as discussed above.

7. Satellite Cells in the Context of the Muscular Dystrophies

Different hypothesis and mechanisms are proposed to explain the muscular degeneration that occurs in patients bearing mutations in a wide number of genes important to muscle structure and function [135, 136]. As the dystrophic muscle is persistently injured, the regenerative process is consistently activated, recruiting satellite cells at higher rates than in normal tissue. Nevertheless, in dystrophic muscle, the regeneration is not complete and there is a progressive replacement of muscle by fibrofatty tissue. Thus, the ability of stem cells to repair the muscle is not sufficient to compensate for degeneration. Three scenarios are proposed to explain this limited regenerative capacity [135].

First, the repetitive cycles of replication would lead SCs to senescence, due to telomere shortening. The presence of shortened telomeres was observed in DMD (Duchenne Muscular Dystrophy) and LGMD2C (limb-girdle muscular dystrophy type 2C) patients [137, 138] and in Dmd mdx mice [139]. Dmd mdx mice lacking telomerase activity develop a phenotype more faithful to muscular dystrophy in humans, including a worsening with aging [140]. However this is controversial, as another study could not detect a significant telomere shortening [141].

Second, the differentiation could not be adequate. Early studies showed that myoblasts from DMD patients delay to fuse and present an abnormal differentiation [142, 143]. In some types of muscular dystrophy, the mutated gene is not expressed in SCs and thus does not influence directly on their function [144]. However, there is also evidence that the primary mutation itself can impair the SC function by reducing its number and causing premature senescence, implicating SC as directly involved in the disease mechanism [145]. Alterations in signaling pathways are also underlying the regenerative potential of SCs. In a knock-in conditional mouse in which Notch signaling is blocked in SCs, the muscle develops a typical dystrophic phenotype with impaired regeneration [146]. The SCs of this mouse showed reduced activation and proliferation, but enhanced differentiation, corroborating the previous studies about the role of Notch signaling in quiescence maintenance [146]. In Dmd mdx mouse, the Notch signaling is attenuated, which diminishes SCs self-renewal and the constitutive activation of Notch recovered the self-renewal capacity, but this is not sufficient to improve regeneration, probably because of MyoD and myogenin inhibition [111].

Dystrophin is expressed in differentiated myofibers, but not in proliferating myoblasts thus it was believed that it was not expressed in satellite cells either. However, a recently published paper elegantly showed that dystrophin is indeed expressed by satellite cells and that it plays an essential role in the regulation of their polarity and asymmetric division. In the absence of dystrophin, there is a reduction in the number of asymmetric divisions and more abnormal divisions, which lead to a decrease in the quantity of myogenic progenitors and thus a failure in muscle regeneration [147]. This work adds a major role for satellite cells dysfunction in the pathophysiology of DMD, which has direct implications for therapies. Third, the dystrophic niche is not favorable for regeneration. In the dystroglycanopathy mouse model Large myd , an increased number of SCs were found in freshly isolated single fibers, related to control mouse [148]. As long as SCs remained attached to the fibers, their proliferative capacity was seen to be reduced, but after total isolation they proliferated and differentiated at levels comparable to normal control, indicating an important role of the niche to stem cell function [148]. In this mouse model, the basal lamina composed by an excess of fibronectin and collagen acts as an obstacle to proper SC proliferation. This work contradicts a former one which suggested that as SC also expresses dystroglycan, the glycosylation defect would also affect its function, impairing regeneration [149]. Even though a recent publication reinforces that the regenerative capacity is not affected in muscles with glycosylation deficiency, the inability to overcome the degeneration is more related to the depletion of regenerative capacity due to excessive and progressive degeneration that occurs in muscular dystrophies than to an inherent defect in SC function itself [150].

By testing the effects of irradiation and myotoxins in the engraftment of donor SCs in nude Dmd mdx mouse it was found that when the host SC pool is still preserved, the engraftment is poor in contrast, when the host SC pool is incapacitated by irradiation, but the stem cell niche is preserved, the donor cell is able to repopulate and regenerate the muscle [151]. Boldrin et al. investigated the regenerative potential of SCs isolated from young and old Dmd mdx mice. They found that both young and aged SCs are able to regenerate the muscle of preirradiated young nude Dmd mdx , reinforcing the notion that the SC function is preserved and that the dystrophic environment, instead of an inherent defect, influences it negatively [152]. The main message of these works is that for future cell therapies it will be interesting to capacitate the host stem cell pool, as well as the preservation/amelioration of a functional niche, to obtain successful results.

An important study performed in several animal models also gave an insight into how the satellite cells are regulated in a context of muscular dystrophies [153]. In the SJL/L mouse model for the limb-girdle muscular dystrophy type 2B the levels of MyoD and Myf5 were found to be downregulated, which indicates that in this animal the satellite cells remain quiescent, which is expected since the histopathology of this animal shows no evidence of the degeneration and regeneration process. This same downregulation was found in the animal Large myd , which is consistent with previous results that shows that the mutation in this animal could interfere with the satellite cell functioning and self-renewal [149]. On the other hand, the animal models Dmd mdx and Lama2 dy-2J /J, the models for congenital muscular dystrophy type 1A, showed enhanced expression levels of MyoD and Myf5, indicating that in these models the satellite cells are activated, which is consistent with the presence of regeneration areas in their histology.

8. Therapies

Since the identification of stem cells, the most promising therapy for muscle wasting diseases has been the cell therapy. The first myoblast transplantation was done in the late 1970s when it was shown that donor myoblasts were able to fuse within host myofibers [154]. One decade later, the demonstration that donor myoblasts restored dystrophin expression in Dmd mdx myofibers [155] opened the precedent for many human clinical trials [156–163] nevertheless, the results were not satisfactory, mainly by the reduced regenerative potential of myoblasts, once they are more committed and differentiated in comparison to SCs.

Entire myofibers can be grafted into host muscle where SCs attached to donor myofibers contribute to muscle regeneration [46]. The advantages of myofiber transplant are as follows: a maximal engraftment is required, a minimal number of cells are required, and the cells are transplanted together with their niche, although these are not easy to apply in clinics [164].

SCs isolated by flow cytometry were transplanted in Dmd mdx mice and it was seen that they engrafted into their muscles and also contributed to the SC compartment, but if the cells were cultured before transplantation, their regenerative potential was reduced [165]. The transplantation of a single luciferase-expressing SC helped to verify the fact that it can self-renew and differentiate, demonstrating the relevance of a careful selection of which cell to use given the high population heterogeneity [166]. Taken together, the studies about direct isolation and transplantation of SCs show the advantages of the requirement of a low number of cells, efficient engraftment, and the repopulation of the host niche with new SCs in contrast, the migration of transplanted cells is limited, only a small number of cells are isolated, and they cannot be maintained for a long time in vitro [164].

Therefore, the use of progenitor cells like SCs is more promising with the advantage of also replenishing the stem cell pool with the possibility of a sustained response. However, the use of these cells in therapy is still not a reality and many challenges remain to be overcome. These include selection of the most suitable subpopulation, optimal culture conditions, and modulation of signaling pathways that control quiescence and self-renewal and delivery of the cells. The choice between systemic and local injections must consider specific features of each disease, like disease severity and the number and size of affected muscles. Still, both strategies have their limitations and issues including homing, engraftment, and long-term survival. Thus, given all the aspects to be dealt and the divergence between in vitro and in vivo results, the combination of different strategies would be more promising.

9. Conclusion

Satellite cells are the first in line for muscle regeneration, and so they are the most promising target in a cell-based therapy for muscle wasting disorders. As shown throughout this review, they have numerous advantages such as easy identification, self-renewal, and myogenic differentiation, which is well understood, and they have been already tested in a therapeutic context. Nevertheless, many questions remain to be answered and this review aimed to explore some possible aspects that could be considered in order to achieve an efficient cell therapy.

At first, the heterogeneity of this population should be considered, such as choosing the ones with better capacity of self-renewal to replenish the pool in an injured muscle or the ones that could be more prone to differentiation. Additionally, since SCs from different muscles or fibers can be distinct, it is important to consider these aspects in order to treat a specific muscle group, for example. The quiescence and activation process is also an aspect that should be considered, since it can be regulated and used, for instance, to direct activation of resident cells. Finally, with previous studies regarding muscular dystrophies and therapies, it is possible to learn about ideal culture conditions and better ways to deliver cells, for example.

It is important to notice that an issue regarding nomenclature of different types of satellite cells may complicate the data interpretation and comparison across studies, since different terms are sometimes used by authors for the same type of cells, or different cells are referred to them with the same general nomenclature. It is possible, therefore, that authors are dealing with the same entities but naming them differently. Hence, it would be valuable if the scientific community found a consensus concerning the diversity of the various cell populations studied.

Major hurdles still have to be dealt with, such as the wide distribution of skeletal muscles within the body and the effect of genetic defects in resident cells however, this review proposes that the knowledge of the satellite cells basic biology may help in the development of further cell-based therapies.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Authors’ Contribution

Camila F. Almeida and Stephanie A. Fernandes contributed equally to this work.


This work was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo-Centro de Pesquisa, Inovação e Difusão (FAPESP-CEPID), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-INCT), Financiadora de Estudos e Projetos (FINEP), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Comitê Francês de Avaliação da Cooperação Universitária com o Brasil (CAPES-COFECUB).


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Copyright © 2016 Camila F. Almeida et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Skeletal Muscle Stages

Myoblast - individual progenitor cells

Myotube - multinucleated, but undifferentiated contractile apparatus (sarcomere)

Myofibre (myofiber, muscle cell) - multinucleated and differentiated sarcomeres

  • primary myofibres - first-formed myofibres, act as a structural framework upon which myoblasts proliferate, fuse in linear sequence
  • secondary myofibers - second later population of myofibres that form surrounding the primary fibres.


The word "biomechanics" (1899) and the related "biomechanical" (1856) come from the Ancient Greek βίος bios "life" and μηχανική, mēchanikē "mechanics", to refer to the study of the mechanical principles of living organisms, particularly their movement and structure. [3]

Biofluid mechanics Edit

Biological fluid mechanics, or biofluid mechanics, is the study of both gas and liquid fluid flows in or around biological organisms. An often studied liquid biofluid problem is that of blood flow in the human cardiovascular system. Under certain mathematical circumstances, blood flow can be modeled by the Navier–Stokes equations. In vivo whole blood is assumed to be an incompressible Newtonian fluid. However, this assumption fails when considering forward flow within arterioles. At the microscopic scale, the effects of individual red blood cells become significant, and whole blood can no longer be modeled as a continuum. When the diameter of the blood vessel is just slightly larger than the diameter of the red blood cell the Fahraeus–Lindquist effect occurs and there is a decrease in wall shear stress. However, as the diameter of the blood vessel decreases further, the red blood cells have to squeeze through the vessel and often can only pass in a single file. In this case, the inverse Fahraeus–Lindquist effect occurs and the wall shear stress increases.

An example of a gaseous biofluids problem is that of human respiration. Recently, respiratory systems in insects have been studied for bioinspiration for designing improved microfluidic devices. [4]

Biotribology Edit

Biotribology is the study of friction, wear and lubrication of biological systems especially human joints such as hips and knees. [5] [6] In general, these processes are studied in the context of Contact mechanics and tribology.

Additional aspects of biotribology include analysis of subsurface damage resulting from two surfaces coming in contact during motion, i.e. rubbing against each other, such as in the evaluation of tissue-engineered cartilage. [7]

Comparative biomechanics Edit

Comparative biomechanics is the application of biomechanics to non-human organisms, whether used to gain greater insights into humans (as in physical anthropology) or into the functions, ecology and adaptations of the organisms themselves. Common areas of investigation are Animal locomotion and feeding, as these have strong connections to the organism's fitness and impose high mechanical demands. Animal locomotion, has many manifestations, including running, jumping and flying. Locomotion requires energy to overcome friction, drag, inertia, and gravity, though which factor predominates varies with environment. [ citation needed ]

Comparative biomechanics overlaps strongly with many other fields, including ecology, neurobiology, developmental biology, ethology, and paleontology, to the extent of commonly publishing papers in the journals of these other fields. Comparative biomechanics is often applied in medicine (with regards to common model organisms such as mice and rats) as well as in biomimetics, which looks to nature for solutions to engineering problems. [ citation needed ]

Computational biomechanics Edit

Computational biomechanics is the application of engineering computational tools, such as the Finite element method to study the mechanics of biological systems. Computational models and simulations are used to predict the relationship between parameters that are otherwise challenging to test experimentally, or used to design more relevant experiments reducing the time and costs of experiments. Mechanical modeling using finite element analysis has been used to interpret the experimental observation of plant cell growth to understand how they differentiate, for instance. [8] In medicine, over the past decade, the Finite element method has become an established alternative to in vivo surgical assessment. One of the main advantages of computational biomechanics lies in its ability to determine the endo-anatomical response of an anatomy, without being subject to ethical restrictions. [9] This has led FE modeling to the point of becoming ubiquitous in several fields of Biomechanics while several projects have even adopted an open source philosophy (e.g. BioSpine). [ citation needed ]

Experimental biomechanics Edit

Experimental biomechanics is the application of experiments and measurements in biomechanics.

Continuum biomechanics Edit

The mechanical analysis of biomaterials and biofluids is usually carried forth with the concepts of continuum mechanics. This assumption breaks down when the length scales of interest approach the order of the micro structural details of the material. One of the most remarkable characteristic of biomaterials is their hierarchical structure. In other words, the mechanical characteristics of these materials rely on physical phenomena occurring in multiple levels, from the molecular all the way up to the tissue and organ levels. [ citation needed ]

Biomaterials are classified in two groups, hard and soft tissues. Mechanical deformation of hard tissues (like wood, shell and bone) may be analysed with the theory of linear elasticity. On the other hand, soft tissues (like skin, tendon, muscle and cartilage) usually undergo large deformations and thus their analysis rely on the finite strain theory and computer simulations. The interest in continuum biomechanics is spurred by the need for realism in the development of medical simulation. [10] : 568

Plant biomechanics Edit

The application of biomechanical principles to plants, plant organs and cells has developed into the subfield of plant biomechanics. [11] Application of biomechanics for plants ranges from studying the resilience of crops to environmental stress [12] to development and morphogenesis at cell and tissue scale, overlapping with mechanobiology. [8]

Sports biomechanics Edit

In sports biomechanics, the laws of mechanics are applied to human movement in order to gain a greater understanding of athletic performance and to reduce sport injuries as well. It focuses on the application of the scientific principles of mechanical physics to understand movements of action of human bodies and sports implements such as cricket bat, hockey stick and javelin etc. Elements of mechanical engineering (e.g., strain gauges), electrical engineering (e.g., digital filtering), computer science (e.g., numerical methods), gait analysis (e.g., force platforms), and clinical neurophysiology (e.g., surface EMG) are common methods used in sports biomechanics. [13]

Biomechanics in sports can be stated as the muscular, joint and skeletal actions of the body during the execution of a given task, skill and/or technique. Proper understanding of biomechanics relating to sports skill has the greatest implications on: sport's performance, rehabilitation and injury prevention, along with sport mastery. As noted by Doctor Michael Yessis, one could say that best athlete is the one that executes his or her skill the best. [14]

Other applied subfields of biomechanics include Edit

Antiquity Edit

Aristotle, a student of Plato can be considered the first bio-mechanic, because of his work with animal anatomy. Aristotle wrote the first book on the motion of animals, De Motu Animalium, or On the Movement of Animals. [15] He not only saw animals' bodies as mechanical systems, but pursued questions such as the physiological difference between imagining performing an action and actually doing it. [16] In another work, On the Parts of Animals, he provided an accurate description of how the ureter uses peristalsis to carry urine from the kidneys to the bladder. [10] : 2

With the rise of the Roman Empire, technology became more popular than philosophy and the next bio-mechanic arose. Galen (129 AD-210 AD), physician to Marcus Aurelius, wrote his famous work, On the Function of the Parts (about the human body). This would be the world's standard medical book for the next 1,400 years. [17]

Renaissance Edit

The next major biomechanic would not be around until 1452, with the birth of Leonardo da Vinci. Da Vinci was an artist and mechanic and engineer. He contributed to mechanics and military and civil engineering projects. He had a great understanding of science and mechanics and studied anatomy in a mechanics context. He analyzed muscle forces and movements and studied joint functions. These studies could be considered studies in the realm of biomechanics. Leonardo da Vinci studied anatomy in the context of mechanics. He analyzed muscle forces as acting along lines connecting origins and insertions, and studied joint function. Da Vinci tended to mimic some animal features in his machines. For example, he studied the flight of birds to find means by which humans could fly and because horses were the principal source of mechanical power in that time, he studied their muscular systems to design machines that would better benefit from the forces applied by this animal. [18]

In 1543, Galen's work, On the Function of the Parts was challenged by Andreas Vesalius at the age of 29. Vesalius published his own work called, On the Structure of the Human Body. In this work, Vesalius corrected many errors made by Galen, which would not be globally accepted for many centuries. With the death of Copernicus came a new desire to understand and learn about the world around people and how it works. On his deathbed, he published his work, On the Revolutions of the Heavenly Spheres. This work not only revolutionized science and physics, but also the development of mechanics and later bio-mechanics. [17]

Galileo Galilei, the father of mechanics and part time biomechanic was born 21 years after the death of Copernicus. Galileo spent many years in medical school and often questioned everything his professors taught. He found that the professors could not prove what they taught so he moved onto mathematics where everything had to be proven. Then, at the age of 25, he went to Pisa and taught mathematics. He was a very good lecturer and students would leave their other instructors to hear him speak, so he was forced to resign. He then became a professor at an even more prestigious school in Padua. His spirit and teachings would lead the world once again in the direction of science. Over his years of science, Galileo made a lot of biomechanical aspects known. For example, he discovered that "animals' masses increase disproportionately to their size, and their bones must consequently also disproportionately increase in girth, adapting to loadbearing rather than mere size. The bending strength of a tubular structure such as a bone is increased relative to its weight by making it hollow and increasing its diameter. Marine animals can be larger than terrestrial animals because the water's buoyancy relieves their tissues of weight." [17]

Galileo Galilei was interested in the strength of bones and suggested that bones are hollow because this affords maximum strength with minimum weight. He noted that animals' bone masses increased disproportionately to their size. Consequently, bones must also increase disproportionately in girth rather than mere size. This is because the bending strength of a tubular structure (such as a bone) is much more efficient relative to its weight. Mason suggests that this insight was one of the first grasps of the principles of biological optimization. [18]

In the 17th century, Descartes suggested a philosophic system whereby all living systems, including the human body (but not the soul), are simply machines ruled by the same mechanical laws, an idea that did much to promote and sustain biomechanical study.

Industrial era Edit

The next major bio-mechanic, Giovanni Alfonso Borelli, embraced Descartes' mechanical philosophy and studied walking, running, jumping, the flight of birds, the swimming of fish, and even the piston action of the heart within a mechanical framework. He could determine the position of the human center of gravity, calculate and measure inspired and expired air volumes, and he showed that inspiration is muscle-driven and expiration is due to tissue elasticity.

Borelli was the first to understand that "the levers of the musculature system magnify motion rather than force, so that muscles must produce much larger forces than those resisting the motion". [17] Influenced by the work of Galileo, whom he personally knew, he had an intuitive understanding of static equilibrium in various joints of the human body well before Newton published the laws of motion. [19] His work is often considered the most important in the history of bio-mechanics because he made so many new discoveries that opened the way for the future generations to continue his work and studies.

It was many years after Borelli before the field of bio-mechanics made any major leaps. After that time, more and more scientists took to learning about the human body and its functions. There are not many notable scientists from the 19th or 20th century in bio-mechanics because the field is far too vast now to attribute one thing to one person. However, the field is continuing to grow every year and continues to make advances in discovering more about the human body. Because the field became so popular, many institutions and labs have opened over the last century and people continue doing research. With the Creation of the American Society of Bio-mechanics in 1977, the field continues to grow and make many new discoveries. [17]

In the 19th century Étienne-Jules Marey used cinematography to scientifically investigate locomotion. He opened the field of modern 'motion analysis' by being the first to correlate ground reaction forces with movement. In Germany, the brothers Ernst Heinrich Weber and Wilhelm Eduard Weber hypothesized a great deal about human gait, but it was Christian Wilhelm Braune who significantly advanced the science using recent advances in engineering mechanics. During the same period, the engineering mechanics of materials began to flourish in France and Germany under the demands of the industrial revolution. This led to the rebirth of bone biomechanics when the railroad engineer Karl Culmann and the anatomist Hermann von Meyer compared the stress patterns in a human femur with those in a similarly shaped crane. Inspired by this finding Julius Wolff proposed the famous Wolff's law of bone remodeling. [20]

The study of biomechanics ranges from the inner workings of a cell to the movement and development of limbs, to the mechanical properties of soft tissue, [7] and bones. Some simple examples of biomechanics research include the investigation of the forces that act on limbs, the aerodynamics of bird and insect flight, the hydrodynamics of swimming in fish, and locomotion in general across all forms of life, from individual cells to whole organisms. With growing understanding of the physiological behavior of living tissues, researchers are able to advance the field of tissue engineering, as well as develop improved treatments for a wide array of pathologies including cancer. [21] [ citation needed ]

Biomechanics is also applied to studying human musculoskeletal systems. Such research utilizes force platforms to study human ground reaction forces and infrared videography to capture the trajectories of markers attached to the human body to study human 3D motion. Research also applies electromyography to study muscle activation, investigating muscle responses to external forces and perturbations. [22]

Biomechanics is widely used in orthopedic industry to design orthopedic implants for human joints, dental parts, external fixations and other medical purposes. Biotribology is a very important part of it. It is a study of the performance and function of biomaterials used for orthopedic implants. It plays a vital role to improve the design and produce successful biomaterials for medical and clinical purposes. One such example is in tissue engineered cartilage. [7] The dynamic loading of joints considered as impact is discussed in detail by Emanuel Willert. [23]

It is also tied to the field of engineering, because it often uses traditional engineering sciences to analyze biological systems. Some simple applications of Newtonian mechanics and/or materials sciences can supply correct approximations to the mechanics of many biological systems. Applied mechanics, most notably mechanical engineering disciplines such as continuum mechanics, mechanism analysis, structural analysis, kinematics and dynamics play prominent roles in the study of biomechanics. [24]

Usually biological systems are much more complex than man-built systems. Numerical methods are hence applied in almost every biomechanical study. Research is done in an iterative process of hypothesis and verification, including several steps of modeling, computer simulation and experimental measurements.


The muscular and skeletal systems provide support to the body and allow for a wide range of movement. The bones of the skeletal system protect the body’s internal organs and support the weight of the body. The muscles of the muscular system contract and pull on the bones, allowing for movements as diverse as standing, walking, running, and grasping items.

Injury or disease affecting the musculoskeletal system can be very debilitating. In humans, the most common musculoskeletal diseases worldwide are caused by malnutrition. Ailments that affect the joints are also widespread, such as arthritis, which can make movement difficult and—in advanced cases—completely impair mobility. In severe cases in which the joint has suffered extensive damage, joint replacement surgery may be needed.

Progress in the science of prosthesis design has resulted in the development of artificial joints, with joint replacement surgery in the hips and knees being the most common. Replacement joints for shoulders, elbows, and fingers are also available. Even with this progress, there is still room for improvement in the design of prostheses. The state-of-the-art prostheses have limited durability and therefore wear out quickly, particularly in young or active individuals. Current research is focused on the use of new materials, such as carbon fiber, that may make prostheses more durable.

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    TEXTBOOK KSSM Biology Form 4 (DLP)

    5.3 Application of Enzymes in Daily Life CHAPTER 5 Enzymes have long been widely used in the commercial sector and for everyday use. The enzymes used are extracted from natural resources such as bacteria or are produced synthetically. Immobilized enzymes are enzymes that combine with inert and insoluble substances to increase the resistance of enzymes towards change in factors such as pH and temperature. With this method, the enzyme molecules will remain in the same position throughout the catalytic reaction and then be separated easily from its product. This technology is known as immobilized enzyme technology. This technology is used in various industrial applications (Photograph 5.1). 5.2Formative Practice 1 How are enzymes produced? 2 How does immobilized enzyme technology help to accelerate the enzyme reaction? 3 Give examples of industries that use enzymes in the manufacturing of products. Digestive enzymes are used in the medical sector Pectinase and Amylase, lipase, cellulase enzymes are protease and cellulase used in juice production enzymes in bio detergent Lactose Trypsin enzyme extracts enzymes fur from animal hide to make are used in leather products lactose-free milk Protease enzyme separates the fish skin PHOTOGRAPH 5.1 Enzyme 95 immobilization technology is used in various industrial application 5.3.1 BioT4(7th)-B5-FA_EN New 5th.indd 95 11/13/2019 12:02:46 AM

    Summary METABOLISM AND ENZYMES Metabolism Enzyme Application of Enzymes in Daily • Anabolism • Enzyme nomenclature: adding -ase to the • Catabolism substrate Life • General characteristics of enzymes • Digestive • Intracellular and extracellular enzymes enzymes • Enzyme action mechanism—‘lock and key’ • Lactose-free hypothesis milk and fruit • Factors that influence the enzyme action juice – Temperature – pH • Bio detergent – Substrate concentration • Leather product – Enzyme concentration (separate fur from animal hide) Self Reflection Have you mastered the following important concepts? • Types of metabolism • General characteristics of enzymes • Mechanism of enzyme action • Factors that influence the mechanism of enzyme action • Application of enzymes in daily life 96 11/13/2019 12:02:46 AM BioT4(7th)-B5-FA_EN New 5th.indd 96

    Summative Practice 5 1 Some chefs sometimes wrap meat in papaya leaves and the meat is marinated for 5 hours before it is cooked. What is the purpose of wrapping with papaya leaves? 2 Why are apples that have been boiled after they are peeled, do not change colour to brown? 3 (a) Enzymes are used in industries and everyday life. Explain the use of enzymes to extract agar-agar from seaweed. (b) State one function of lipase in the food industry. 4 (a) State two characteristics of enzymes. (b) Explain why only certain substrate can combine with enzymes. (c) (i) What is the hypothesis that is used to explain the mechanism of enzyme action? In this hypothesis, what represents the structure of enzymes and the structure of the substrate? (ii) Which characteristics of enzymes can explain this hypothesis? Essay Questions 5 (a) If you are a food entrepreneur, suggest an enzyme that you can use to process meat and fish. State the function of this enzyme. (b) Discuss how the characteristics of the enzymes can influence its action. Enrichment 6 The enzymes that exist in the bacteria strain which live in hot spring areas can be extracted and added to laundry detergent. Suggest why enzymes from these bacteria are suitable to be used as laundry detergent. 7 Why does cyanide poisoning cause immediate death? 8 Fresh fruits can be processed to produce juice. Fruits are crushed and squeezed before the juice is extracted. Plant cells contain strong cellulose walls. However, if enzymes that contain pectinase enzymes are used, more juice can be extracted. Based on this information, suggest one laboratory experiment that can extract more fruit juice than the pressing method. BioT4(7th)-B5-FA_EN New 5th.indd 97 Complete answers are available by scanning the QR code provided 97 11/13/2019 12:02:46 AM

    CHAPTER 6 Cell Division • Do You KNOW… • How does growth happen? Can identical How does an organism produce organisms be new cells? produced? • cHroewateisd?genetic variation 98 11/21/2019 1:53:14 PM BioT4(NC)-B6-EN New 6th.indd 98

    6.1 Cell Division 6.3 Meiosis 6.1.1 Describe: 6.3.1 State the meaning of • karyokinesis (nuclear 6.3.2 meiosis. 6.3.3 Identify types of cells that division) undergo meiosis. • cytokinesis State the necessity of meiosis in: (cytoplasmic division) • the formation 6.1.2 Describe the terms 6.3.4 of gametes haploid, diploid, (gametogenesis). chromatin, homologous 6.3.5 • producing genetic chromosomes, paternal variation chromosome and 6.3.6 • maintaining diploid maternal chromosome. chromosomal numbers from one generation to 6.2 Cell Cycle and Mitosis another. Explain the stages of 6.2.1 Describe the phases in a meiosis in the correct order: cell cycle: • meiosis I • meiosis Il • interphase Draw and label the cell structure in each stage of • GS 1pphhaassee meiosis I, meiosis II and • cytokinesis. Compare and contrast • MG2 phase meiosis and mitosis. • phase • mitosis • cytokinesis 6.2.2 Arrange the stages of mitosis in the correct order. 6.2.3 Communicate about the cell structure of each 6.4 Issues of Cell Division on Human Health stage of mitosis and cytokinesis by using labelled diagrams. 6.4.1 Explain the effects of abnormal mitosis on 6.2.4 Compare and contrast 6.4.2 human health: • tumour mitosis and cytokinesis in • cancer Evaluate the effects animal and plant cells of abnormal meiosis on Down syndrome 6.2.5 Discuss the necessity of individuals. mitosis in: • development of embryo • growth of organisms • healing of wounds on the skin • regeneration • asexual reproduction BioT4(NC)-B6-EN New 4th.indd 99 99 11/13/2019 12:04:23 AM

    6.1 Cell Division Brainstorm! Cells in our body always grow, divide and die. As such, the dead cells What happens when must be replaced with new cells. Cells in the body produce new cells cells cannot undergo through the cell division process. Cell division involves two stages, that cell division? is karyokinesis and cytokinesis. • Karyokinesis involves the division of the nucleus. • Cytokinesis involves the division of the cytoplasm. The organism’s body cells are divided into somatic cells and reproductive cells or gametes. ORGANISM CELL SOMATIC CELL GAMETE • Body cells apart from gametes. • Gametes are reproductive cells. • Somatic cells are produced • Gametes are produced through through the mitosis process. the meiosis process. • It contains a diploid number • It contains a haploid number of chromosomes, that is, of chromosomes, that is, each cell contains two sets of each cell contains one set of chromosomes or 2n. In human chromosomes or n. In human somatic cells, 2n = 46. gametes, n = 23. In diploid cells, one set of chromosomes originate from the male parent or paternal chromosomes and another set is from the female parent or maternal chromosomes. Both paternal and maternal chromosomes have the same structural characteristics. This pair of chromosomes are called homologous chromosomes (Figure 6.1). Chromatin is a chromosome that looks like a long thread. Haploid (nH)a:plAoiHdca(pnol)opAidyc(onop)yfAoecfoaepacychohfseceathcohrfoscehmtrooomf csohsoroommmeoesome Diploid D(i2plnoi)dD:(ip2Tlnow)idTow(2oncc)ooTppwieoiescsofpeoieasfcohefcaehacrcohhmcochshroomrmoeomsomoesome ICT 6.1 Three chromosomes without pairs Three pairs of homologous chromosomes Importance of (one setThorfeepTpaharitereseropnfahairoslmocoflhhoogrmoouomslocgohorsuoosmcmohsroeommseo,soomnee set of cell division ThreeTchreoemcohsroommeossowmitheosuwt ipthaoirust pairs materna(loncehsr(eootnomef spoeatseoorfnpmaal tceehrsrnoa)ml cohsroommeoss,oomness,eotnoef set of (Accessed on 21 August 2019) 6.1 FIGURE 6.1 Haploid and diploid chrmoamteronmasalotcehmrrnoaeml scohsroommeoss)omes) Formative Practice 1 Give the definition of the following terms: 2 Predict what will happen if the cells in the (a) karyokinesis (c) chromatin reproductive organs of humans are unable to (b) cytokinesis (d) homologous chromosomes produce haploid cells. 100 6.1.1 6.1.2 BioT4(NC)-B6-EN New 4th.indd 100 11/13/2019 12:04:23 AM

    6.2 Cell Cycle and Mitosis What is a cell cycle? The cell cycle refers to the sequence of events that involves DNA multiplication and cell division to produce two daughter cells. The cell cycle consists of interphase and M phase. Interphase is the longest phase in the cell cycle. This phase is made up of the G1, S and G2 phase. S PHASE G1 PHASE 2 DNA synthesis occurs in the S phase. The DNA in the nucleus is replicated. 1 Cells grow. Cell components Each chromosome multiplies into two such as mitochondrion and identical chromosomes known as sister endoplasmic reticulum are chromatids. Both chromatids contain produced at this stage. Proteins the same copy of the DNA molecule. used in the cell cycle are also Both chromatids are joined at the centromeres. INTERPHASE synthesised during this time. At Cytokinesis this stage, the nucleus looks big Mitosis and the chromosome is in the form of chromatin. CHAPTER 6 S G1 G2 M PHASE FIGURE 6.2 Cell cycle M PHASE 4 M phase is made up of mitosis G2 PHASE and cytokinesis. Mitosis 3 The cells will continue to grow and remain active involves prophase, metaphase, manedtambaokliceaflilnyadl uarrirnagngtheemGen2 ptshtaosee.nCteerlltshegantehxetr energy stage anaphase and telophase. of cell division. After the interphase stage, the cell will enter the M phase. 6.2.1 101 BioT4(NC)-B6-EN New 4th.indd 101 11/13/2019 12:04:23 AM

    Our World of Biology Mitosis The failure of mitotic Mitosis is defined as the division of the nucleus of parent cell into two division in somatic nuclei (Photograph 6.1). Each nucleus contains the same number of cells will not be chromosomes and genetic content with the nucleus of parent cell. inherited by the next generation. centriole PROPHASE spindle fibres • In the nucleus, chromatin starts to shorten and thicken to form a chromosome structure that can be seen through a light microscope. • The chromosome is seen to be made up of two centromere identical threads called sister chromatids. • Both sister chromatids are joined at the nucleus membrane centromere. disintegrates • The nucleus membrane disintegrates, the nucleolus disappears, the centriole moves to the opposite poles and the chromosomes spindle fibres start to form. centromere ICT 6.2 anaphase Activity: Design three telophase dimensional models of prophase the mitotic stages PHOTOGRAPH 6.1 Mitosis at the tip of the plant root metaphase 6.2.2 6.2.3 102 11/13/2019 12:04:26 AM BioT4(NC)-B6-EN New 4th.indd 102

    centromere equatorial plane spindle fibres METAPHASE chromosomes • Centrioles are at the opposite chromosomes poles of the cell. • The spindle fibres maintain the chromosomes at the equatorial plane. • The chromosomes become aligned in a single row on the equatorial plane. • Metaphase ends when the centromere begins to divide. ANAPHASE sister chromatids CHAPTER 6 pole of the cells TELOPHASE • The centromere divides • When the chromatids are at the into two and the sister sister chromatids separate. chromatids opposite poles, they are now called the daughter chromosome. • Spindle fibres shorten, 103 • Each pole contains one set contract and the of complete and identical sister chromatids are chromosomes. attracted to the opposite • Chromosomes are shaped again pole cells. as fine chromatin threads. • Nucleoli are formed again. • Anaphase ends when the • Spindle fibres disappear. chromatid arrives at the • A new nucleus pole of the cell. membrane is formed. daughter spindle • The telophase chromosomes fibres stage is followed by cytokinesis. centriole 6.2.2 6.2.3 nuclear membrane nuclear membrane daughter cells FIGURE 6.3 Mitosis BioT4(NC)-B6-EN New 4th.indd 103 11/13/2019 12:04:30 AM

    cleavage furrow microfilaments The differences between mitosis and cytokinesis in animal cells and plant cells contractile ring of Plant cells do not contain centrioles. However, plant cells can still form microfilaments spindle fibres during mitosis. Cytokinesis is different between animal cells and plant cells. Cytokinesis daughter cell is the division of cytoplasm that happens immediately after the nucleus FIGURE 6.4 Cytokinesis in is formed, that is, at the end of telophase. Cytokinesis occurs in animal animal cells cells when the plasma membrane constricts in the middle of the cell between the two nuclei (Figure 6.4). Microfilaments at the point of constriction will contract, causing the cell to constrict until it splits to form two daughter cells. Cytokinesis in plant cells also begins when the formed vesicles combine to form cell plates at the centre of the cell (Figure 6.5). The cell plates are surrounded by a new plasma membrane and a new cell wall substance is formed among the spaces of the cell plates. The cell plates expand outwards until they combine with the plasma membranes. At the end of cytokinesis, cellulose fibres are produced by the cells to strengthen the new cell walls. Two daughter cells are formed. Each cell has a diploid condition. vesicles form cell parent cell wall new cell wall plates cell plate daughter cell FIGURE 6.5 Cytokinesis in plant cells The necessity of mitosis Mitosis is important for the following life processes. For embryo development Through the mitosis process, the and organism growth, mitosis lizard is able to grow a new tail ensures that rapid cell growth (regeneration) if the tail breaks. occurs. When the body is injured, mitosis will Mitosis aids organisms such as produce new cells to replace cells that are hydra to produce new individuals dead or damaged. through the formation of new buds. PHOTOGRAPH 6.2 The necessity of mitosis for living organisms 104 6.2.4 6.2.5 BioT4(NC)-B6-EN New 4th.indd 104 11/13/2019 12:04:32 AM

    Stem cell therapy uses stem In agriculture, the technique of culturing plant cells from bone marrows to treat tissues is used to produce young plants through the damaged cartilage. culturing of parent cells without going through the fertilisation process. The culturing technique uses stem cells from animals which are then cultured in laboratories to produce meat. 6.2Formative Practice 3 Predict what will happen PHOTOGRAPH 6.3 The CHAPTER 6 if the spindle fibres fail to application of mitosis in 1 State the application of develop. the fields of medicine and mitosis in the field of agriculture agriculture. 4 Explain the necessity of mitosis for life processes. 2 Explain the process that occurs during the S phase. 6.3 Meiosis PHOTOGRAPH 6.4 Meiosis is the process of cell division that occurs in reproductive organs to Homologous chromosome produce gametes that contain half the number of chromosomes (haploid) of the parent cells (diploid). Meiosis occurs in the testis (male) and ovary (female) for animals and humans. The need for meiosis Meiosis forms gametes through the process of gametogenesis and ensures that the diploid chromosome number of organisms that carry out sex reproduction is always maintained from one generation to the next. Meiosis also produces genetic variation in the same species. Meiosis is divided into two stages of cell division, that is meiosis I and meiosis II (Figure 6.6). a. Meiosis I comprises of prophase I, metaphase I, anaphase I and telophase I. b. Meiosis II comprises of prophase II, metaphase II, anaphase II and telophase II. 6.3.1 6.3.2 6.3.3 105 BioT4(NC)-B6-EN New 4th.indd 105 11/13/2019 12:04:35 AM

    chiasma non-identical PROPHASE I chromatid • Chromatin shortens, thickens and forms visible chromosomes. The pairing of homologous chromosomes (synapsis) forms bivalent (or known as a tetrad, that is four chromatids for each homologous chromosome). bivalent/ spindle • The crossing over process that is an exchange of genetic material tetrad fibre between non-identical chromatids takes place. Crossing over produces a combination of genes that are new in chromosomes. The point where the chromatids cross over is called chiasma. At the end of prophase I, the nucleus membrane and nucleoli will start to disappear. Both centrioles will move towards the opposite pole cells. Spindle fibres are formed among the centrioles. centriole homologous chromosome sister chromatids separated and pulled to are still tied to the opposite poles centromere plasma membrane constricts equatorial homologous chromosome centriole plane arranged at the equatorial plane FIGURE 6.6 Meiosis METAPHASE I ANAPHASE I TELOPHASE I • The homologous • The spindle fibres • The chromosomes arrive at chromosomes are arranged contract and cause the opposite pole cells. at the equatorial plane. each homologous chromosome to separate • Each polar cell contains • One chromosome from its homologous a number of haploid from each pair of the pair and be pulled to the chromosomes that are homologous chromosome opposite poles. made up of one set of is tied to the spindle fibres chromosomes only. from one pole cell and its • Each chromosome is homologous is tied to the still made up of a pair of • The spindle fibres will then spindle fibres from the sister chromatids tied to disappear. opposite pole cell. a centromere and move as one unit. • Nucleoli will reappear and • The sister chromatids are the nuclear membrane is still tied together because formed. the centromere has not separated. • Telophase I is succeeded by the cytokinesis process that produces two daughter cells. • Both daughter cells produced are in the haploid condition. AR • The interphase for meiosis I is usually short and the DNA does not replicate. 106 6.3.4 6.3.5 BioT4(NC)-B6-EN New 4th.indd 106 11/13/2019 12:04:37 AM

    PROPHASE II ANAPHASE II • The nucleoli and the nuclear • The sister chromatid centromere starts membrane disappear. to separate. • Each chromosome is made • The sister chromatid pair separates up of sister chromatids that and moves towards the opposite poles are joined at the centromere. led by the centromere. • The spindle fibres start to • Each chromatid at this stage is known as form in both daughter cells. a chromosome. sister chromatids separate four haploid daughter cells CHAPTER 6 nuclear membrane two haploid TELOPHASE II daughter cells • Chromosomes arrive at the pole of the cell. METAPHASE II • Spindle fibres disappear. The nuclear membrane and • Chromosomes are arranged at the nucleoli are reconstructed. random on the equatorial plane • The number of chromosome for each daughter cell for each daughter cell. is half the number of parent chromosomes. • Each chromatid is tied to • Telophase II ends with the process of cytokinesis the spindle fibres at the centromere. that produces four daughter cells that are haploid. • Each haploid cell contains half the number of • Metaphase II ends when the centromere separates. parent cell chromosomes. The genetic content is also different from the diploid parent cell. The haploid cells develop into gametes. 6.3.4 6.3.5 107 BioT4(NC)-B6-EN New 4th.indd 107 11/13/2019 12:04:44 AM

    Activity Zone Comparison and contrast between meiosis and mitosis Build a thinking tool to compare and You have learned about two types of cell divisions, that is the mitosis and contrast: meiosis. What is the main event that differentiates mitosis and meiosis (a) meiosis I and and between meiosis I and meiosis II? Compare and contrast the two types of cell division. meiosis II (b) meiosis and 6.3Formative Practice 2 Explain how meiosis I can reduce the number of mitosis 1 State the most obvious chromosomes in the difference between meiosis I daughter cell. 6.4 and meiosis II. ICT 6.3 Issues of Cell Division on Video: Cancer Human Health (Accessed on 21 August 2019) The cell cycle is controlled by a special control system at each G1, S, G2 and M phase to ensure proper division of the cells. However, uncontrolled cell division sometimes can lead to the formation of tumours. Tumour is divided into two types which are benign tumour and malignant tumour. A benign tumour is not dangerous and can be removed surgically. A malignant tumour is also called cancer. Cancer is caused by several factors such as radiation (x-ray, gamma rays and ultraviolet rays), chemical substances (such as tar in tobacco), carcinogens (such as formaldehyde and benzene), genetic factors, and also bacteria and viruses. This will cause the cells to divide continuously and develop into a tumour. The cancer cells will spread and destroy normal cells around them. This condition will affect the functions of the tissues around them. Cancer that is not identified at the early stage can cause damage to the organs and finally death (Figure 6.7). a tumour lymph vessel grandular blood cancer tissues vessel cell The tumour grows Cancer cells compete to get The cancer cells spread A new tumour from a single cell. nutrients from other tissues through the lymph vessels and develops on other around them. blood vessels to other parts of organs. the body. 108 FIGURE 6.7 The development of breast cancer 6.3.6 6.4.1 BioT4(NC)-B6-EN New 4th.indd 108 11/13/2019 12:04:48 AM

    Any abnormality during the division of meiosis can also PHOTOGRAPH 6.5 cause genetic diseases such as Down syndrome. This happens A child with Down syndrome because the spindle fibres fail to function during anaphase I displays certain characteristics or anaphase II. As a result, the chromosome fails to separate such as stunted body growth and (nondisjunction). Gametes will have an abnormal number mental retardation of chromosomes (22 or 24 chromosomes). If fertilisation between a normal gamete (23 chromosomes) and an abnormal chromosome (24 chromosomes) occurs, the zygote will carry 47 chromosomes which is an abnormal condition (Figure 6.8). In a normal meiosis division, If the homologous chromosome or the chromosomes are divided sister chromatids fail to separate, the evenly among the gametes. distribution of parent chromosomes during meiosis will be uneven. The diploid The diploid CHAPTER 6 chromosome number chromosome number in humans in humans 2n = 46 2n = 46 MEIOSIS MEIOSIS The haploid The haploid The haploid nondisjunction PHOTOGRAPH 6.6 number number number during The complete anaphase chromosome set of an n = 23 n = 23 n = 24 individual with Down The haploid syndrome number n = 22 FERTILISATION Diploid chromosome number, 2n +1= 47 ( Three copies of chromosome 21 ) FIGURE 6.8 Formation of trisomy 21 An individual with Down syndrome has 47 chromosomes, which is an extra chromosome at the 21st set. This condition is known as trisomy 21. This syndrome can cause mental retardation, slanted eyes and a slightly protruding tongue. 6.4Formative Practice 1 Explain why radiotherapy is used to control 2 Nondisjunction conditions in humans can or stop the growth of cancer cells. cause genetic diseases such as Down syndrome. State the number of chromosomes and the characteristics that are found in an individual with Down syndrome. 6.4.2 109 BioT4(NC)-B6-EN New 4th.indd 109 11/13/2019 12:04:50 AM

    Summary CELL DIVISION Cell Division Cell Cycle and Mitosis Meiosis Issues of Cell Division on Human Health Karyokinesis M phase Meiosis I and The effects (nuclear division) (mitosis and meiosis II of mitosis cytokinesis) The similarities abnormality: Cytokinesis and differences tumour, cancer (cytoplasmic Interphase between division) G(G21,pShaasned) meiosis and The effects mitosis of meiosis abnormality: Down syndrome Self Reflection Have you mastered the following important concepts? • Definitions of karyokinesis, cytokinesis, haploid, diploid, chromatin, homologous chromosomes, paternal and maternal chromosomes • Cell cycle • Stages of mitosis • The differences bet ween mitosis and cytokinesis bet ween animal cells and plant cells • Stages of meiosis • Differences and similarities bet ween meiosis and mitosis • The need for mitosis and meiosis • The effects of mitosis and meiosis abnormalit y towards human health 110 11/13/2019 12:04:50 AM BioT4(NC)-B6-EN New 4th.indd 110

    Summative Practice 6 1 Name the sequences in the mitosis process. 2 What is the function of the centriole in the division of animal cells? 3 State one difference between mitosis metaphase and meiosis metaphase I. 4 (a) Explain the importance of cell division that happens at the tip of a plant root. (b) A farmer wants to plant a large number of quality breed mango trees in a short time for commercial purposes. State and explain the techniques that can be used by the farmer. 5 Figure 1 shows a cell at stage M in a cell cycle. Draw PPchcrohmroosmomoesome both cells that will be formed if the P chromosome does not separate. FIGURE 1 Answer Essay Questions 6 Figure 2 shows the complete set of chromosomes of an individual. (a) State the genetic disorder this individual has. (b) Explain how this individual is born with this genetic disorder. FIGURE 2 7 Cancer cells are formed after normal cells are exposed to factor Y. (a) Explain the formation of cancer cells. (b) State two examples of factor Y that causes the formation of cancer cells. (c) State two ways to avoid the development of cancer cells. Enrichment 8 The development of plant tissue culture has allowed scientists to improve the quality and quantity of a crop. Scientists in Malaysia have succeeded in patenting a product that can be sprayed on orchid plants to overcome infections caused by a virus. This branch of biotechnology is called RNA interference technology. In your opinion, can the spray technology be used for all organisms as protection against infections? Complete answers are available by scanning the QR code provided 111 BioT4(NC)-B6-EN New 4th.indd 111 11/13/2019 12:04:51 AM

    CHAPTER Cellular 7 Respiration Do you KNOW. • mWehtyabisoelicneprrgoycreesqsu?ired for the • pWrohdaut cistitohneomf aeinnesrguyb?strate in the • aoWWnchdhcaauftter arainmrreeaetetnhhrteoeabtptioyircponrec?esessposfierarsetistohpnairtation? • How is tempe 11/21/2019 1:54:15 PM processed? 112 BioT4(NC)-B7-EN New 7th.indd 112

    7.1 Production of energy through cellular respiration 7.1.1 Justify the necessity of energy in metabolic processes. 7.1.2 Identify the main substrate used in energy production. 7.1.3 List the types of cellular respiration: • aerobic respiration • anaerobic respiration • fermentation 7.2 Aerobic respiration 7.2.1 Conceptualise energy production from glucose during aerobic 7.2.2 respiration in cells. 7.2.3 Write a word equation for aerobic respiration in cells. Conduct an experiment to study aerobic respiration. 7.3 Fermentation 7.3.1 State the factors that cause fermentation to occur in cells. 7.3.2 Explain by using examples of energy production from glucose during fermentation in: • human muscle cells • Lactobacillus 7.3.3 • yeast • plants such as paddy Write and explain word equations for: 7.3.4 • lactic acid fermentation • alcohol fermentation 7.3.5 Conduct an experiment to study fermentation in yeast. Compare and contrast aerobic respiration and fermentation. BioT4(NC)-B7-EN New 6th.indd 113 113 11/13/2019 12:09:23 AM

    7.1 Production of energy through cellular respiration In Chapter 5, you have learned about two types of metabolic reaction, which are anabolism and catabolism. Both of these reactions involve energy. • The catabolism process releases energy. • The anabolism process uses energy. Without energy, the anabolic processes such as protein formation which is the basic muscle substance will not occur. Activity Zone The main substrate in energy production Conduct a group Cellular respiration is carried out to generate the energy needed by all discussion about living cells. Cellular respiration is the oxidation process of organic the energy molecules through several stages to release energy. The main substrate requirements in the for cellular respiration is glucose. Chemical energy found in glucose is metabolic process. released to produce energy required by cells. In humans and animals, glucose is obtained through the digestion of carbohydrates from the food eaten. In green plants, light energy can be trapped by chlorophyll for the photosynthesis process to produce glucose. Types of cellular respiration There are two types of cellular respiration, which are aerobic and anaerobic respiration. Aerobic respiration occurs in the presence of oxygen. Anaerobic respiration occurs in the absence of oxygen. Fermentation is an alternative pathway of obtaining energy besides cellular respiration. In fermentation, the breakdown of glucose is incomplete in conditions of limited oxygen or without oxygen. This chapter focuses only on aerobic respiration and fermentation. 7.1Formative Practice 4 Explain how humans, animals and plants acquire glucose to produce energy. 1 Give five examples of the necessity of energy in a metabolic process. 2 State the main substrate in the production of energy. 3 State the meaning of cellular respiration and the types of cellular respiration. 114 7.1.1 7.1.2 7.1.3 BioT4(NC)-B7-EN New 6th.indd 114 11/13/2019 12:09:24 AM

    7.2 Aerobic Respiration ICT 7.1 Aerobic respiration is the breakdown of glucose involving oxygen to Video: Aerobic respiration produce chemical energy. Oxygen is used to oxidise glucose to produce (Accessed on 21 August 2019) carbon dioxide, water and energy. The aerobic respiration process begins with the glycolysis process. Brainstorm! Glycolysis means the breakdown of glucose by enzymes. This process The number of occurs in the cytoplasm. One glucose molecule is broken down into two mitochondrion pyruvate molecules. in the muscle The following process occurs in the mitochondrion. Pyruvate produced cells of an athlete from glycolysis is then oxidised through a series of reactions to produce increases after carbon dioxide, water and energy. A large amount of this energy is used intensive training. to produce adenosine triphosphate (ATP) molecules. Explain how this contributes to Glycolysis Oxidation of Pyruvate the achievement of the athlete as Glucose Pyruvate Carbon dioxide + water + energy compared with (Occurs in the mitochondrion) those who do not (Occurs in the cytoplasm) CHAPTER 7 undergo intensive training. The aerobic respiration is simplified as follows. • ATP molecules are produced when a group of non-organic phosphate is added to adenosine diphosphate (ADP). ADP + phosphate energy ATP • ATP molecules have weak phosphate links. • When the phosphate links on ATP molecules are broken, the energy released is supplied to cells to help us carry out our daily activities. energy ATP ADP + phosphate The complete process of glucose oxidation is simplified as follows: Word equation: Carbon dioxide + water + energy Glucose + oxygen (2898 kJ) 7.2.1 7.2.2 115 BioT4(NC)-B7-EN New 6th.indd 115 11/13/2019 12:09:28 AM

    seAi1tci.vt2ivtcitAy 7.1 To study aerobic respiration Experiment Problem statement Do living organisms carry out aerobic respiration? Hypothesis Take Note! Living organisms use oxygen and release carbon dioxide during aerobic respiration. Wipe all connectors with petroleum jelly Variable to ensure that the Manipulated: Presence of living organisms apparatus prepared Responding: Increase in the level of coloured liquid is airtight. Fixed: Initial level of coloured liquid Materials Water, coloured liquid, soda lime, living organism (cockroach) and petroleum jelly Apparatus Boiling tubes, screw clip, wire gauze, 250 ml beaker, capillary tube, ruler, rubber tube and water bath screw clip Biological Lens rubber tube The apparatus set-up is called a capillary tube capillary tube respirometer. It is boiling tube B used to measure the boiling tube A rate of respiration cockroach level of coloured of an organism by wire gauze liquid estimating the rate of oxygen used. level of coloured liquid soda lime water bath to maintain temperature Apparatus set-up to study aerobic respiration process Procedure 1 Prepare the apparatus as shown in the figure above. 2 Prepare two boiling tubes labelled A and B. 3 Fill both boiling tubes with 10 g soda lime. 4 Put the wire gauze in the middle of boiling tube A. 5 Put a cockroach on the wire gauze in boiling tube A while the boiling tube B is left empty. 6 Wipe all connections of the apparatus with petroleum jelly. 7 Close the screw clip and mark the height of the initial level of the coloured liquid in the capillary tube for both boiling tubes. 8 Leave the apparatus for an hour. 9 Measure and record the final height of the coloured liquid in both capillary tubes after an hour with a ruler. 10 Record your observations in the following table. 116 7.2.3 BioT4(NC)-B7-EN New 6th.indd 116 11/13/2019 12:09:28 AM

    Results Initial level (cm) Final level (cm) Difference in levels Boiling tube (cm) A B Discussion 1 What is the purpose of preparing boiling tube B? 2 What is the function of soda lime in the boiling tube? 3 Is there a change in the level of coloured liquid in capillary tube A? Explain your answer. Conclusion Is the hypothesis accepted? Suggest a suitable conclusion. 7.2Formative Practice CHAPTER 7 1 State the meaning of aerobic respiration. 3 State the word equation for aerobic respiration. 2 Suggest another substrate apart from glucose that can be used by cells for cellular 4 Describe the processes involved in aerobic respiration. respiration to produce energy. 7.3 Fermentation Fermentation is the incomplete breakdown of glucose in conditions of limited oxygen or without oxygen. Fermentation is different from aerobic respiration in its metabolic pathway after the glycolysis stage. After glycolysis, the pyruvate produced will undergo either alcohol fermentation or lactic acid fermentation. 7.3.1 117 BioT4(NC)-B7-EN New 6th.indd 117 11/13/2019 12:09:30 AM

    FERMENTATION The incomplete breakdown of glucose in limited or no oxygen conditions. ICT 7.2 ALCOHOL FERMENTATION The incomplete breakdown of glucose to ethanol, carbon dioxide and energy. Video: Anaerobic respiration (Accessed on 21 August 2019) Glucose Ethanol + carbon dioxide + energy (210 kJ) YEAST PLANTS • Ethanol is used in the making of • Paddy plants that grow in waterlogged areas with less beer and wine. oxygen are able to carry out alcohol fermentation. • The released carbon dioxide makes • Ethanol produced in the tissues during the bread dough rise. fermentation process is toxic to most plants but the cells of paddy plants have a higher tolerance for ethanol compared to other species. • Paddy plants produce plenty of alcohol dehydrogenase . enzymes that can break down ethanol molecules into non-toxic carbon dioxide. seAitc1itv.ii2vtictAy 7.2 Produce and market food products Project produced through fermentation Procedure 1 Your teacher will divide your class into a few groups. 2 Each group will choose one food product that is produced through the fermentation process and market that product in school. Examples of products are tapai, yoghurt or bread. 3 Each group needs to prepare a proposal before starting the project. The proposal must contain: • introduction of the project including the objectives • execution cost • production and marketing plan • expected outcome 4 If necessary, get advice from your teacher or parents to ensure the smooth delivery of the project. 5 Conduct the project as planned. 6 At the end of the project, each group must prepare a complete report. 118 7.3.2 7.3.3 BioT4(NC)-B7-EN New 6th.indd 118 11/13/2019 12:09:33 AM

    Lactobacillus bacteria LACTIC ACID FERMENTATION The breakdown of glucose into lactic acid and energy. Glucose Lactic acid + energy LACTOBACILLUS Brainstorm! • The bacteria Lactobacillus carries out milk fermentation to Some bacteria produce yoghurt. can only survive in anaerobic • Lactobacillus acts on the lactose (milk sugar) and turns it into conditions. Predict lactic acid. what can happen to this type of bacteria • The lactic acid will then coagulate casein (milk protein) to when oxygen is produce yoghurt. supplied. • Lactic acid is the source of a sour taste in yoghurt. oxygen intake CHAPTER 7HUMAN MUSCLE CELLS • This process is carried out by the muscle cells during vigorous training. • During vigorous training, the rate of oxygen used exceeds the oxygen supplied by the blood circulatory system. • The muscle is in an oxygen-deficiency state and is said to undergo oxygen debt. • During this process, glucose cannot break down completely. For each glucose molecule that is broken down, only two ATP molecules or 150 kJ energy will be produced. • The produced lactic acid accumulates until it reaches a level of concentration that can cause fatigue and muscle cramps. • Once the vigorous activity stops, exercise recovery the intake of excess oxygen will oxidise the lactic acid into lack of oxygen (oxygen debt) carbon dioxide, water and energy. When all the lactic acid has been expelled, the oxygen debt is repaid. • Figure 7.1 shows a lack oxygen intake of oxygen in muscles during exercise and oxygen debt is repaid. oxygen debt repaid at the beginning at the end at the end of exercise of exercise of recovery Time (minutes) FIGURE 7.1 Lack of oxygen in muscles and oxygen debt repaid 7.3.2 7.3.3 119 BioT4(NC)-B7-EN New 6th.indd 119 11/13/2019 12:09:39 AM

    1.2 7.3AscetitivivititycA To study the process of yeast fermentation Experiment Problem statement What are the products of yeast fermentation? Hypothesis Yeast fermentation produces energy, carbon dioxide and ethanol. Variables Take Note! Manipulated: Presence of yeast Responding: Changes in temperature, lime water and ethanol smell Ensure that the end Fixed: The volume of boiled glucose solution and the anaerobic condition of the delivery tube is soaked in lime water. Materials 5% yeast suspension, 5% boiled glucose solution, lime water and paraffin oil Apparatus delivery delivery Boiling tube, test tube, thermometer, measuring cylinder, delivery tube tube thermometer thermometer tube and cork boiling boiling Procedure tube A 10 20 30 40 50 60 70 80 90 100 110 paraffin tube B 1 Fill 2 boiling tubes with 15 ml of 5% glucose solution that has oil 5% boiled glucose 5% boiled been boiled and left to cool. solution + yeast lime glucose suspension water solution 2 Label the boiling tubes as A and B. -10 0 3 Put 5 ml 5% yeast suspension into boiling tube A. 4 Add paraffin oil into both of the boiling tubes. 5 Close both boiling tubes with the cork that has a hole and delivery raedspeelivcetirvyetlyu.bDei.pPtrheepaerned2otfeedtsueabtlicevtehurbydeeslivweirtyh tube tube that contains lime watethr.ermometer 2 ml of lime water thermometer tube into each test 10 20 30 40 50 60 70 80 90 100 110 boiling 10 20 30 40 50 60 70 80 90 100 110 6 Leave the apparatus for 1 houtburo.bileinAg tube B 7 Measure and record the initial and final tempepraartauffrine using a 5% boiled paraffin thermometer. glucose oil 5% boiled glucose -10 0 oil solution -10 0 lime 8 Record your observationsssouinsluptteiohnnesi+otnyaebalset below. lime water water Results Apparatus set-up to study the yeast fermentation process Boiling tube Temperature (°C) Smell of solution A Beginning of End of Change in lime water B experiment experiment Discussion 1 How is the anaerobic condition maintained to ensure that the fermentation process is complete? 2 What is the function of preparing boiling tube B? 120 7.3.4 BioT4(NC)-B7-EN New 6th.indd 120 11/13/2019 12:09:40 AM

    3 What is the purpose of boiling the glucose solution earlier? 4 How do the results show that fermentation has taken place in boiling tube A? Conclusion Is the hypothesis accepted? Suggest a suitable conclusion. Comparison between aerobic respiration and fermentation There are a few similarities and differences between fermentation and aerobic respiration (Figure 7.2 and Table 7.1). The breakdown The process Occurs in yeast, Brainstorm! process of glucose begins in the bacteria, animals and its conversion cytoplasm and plants Why is aerobic to chemical energy respiration more suitable for yeast SIMILARITIES BETWEEN AEROBIC RESPIRATION AND compared with CHAPTER 7 FERMENTATION fermentation? Produces chemical energy The process begins with glycolysis when in the form of ATP glucose is converted to pyruvate FIGURE 7.2 Similarities between aerobic respiration and fermentation TABLE 7.1 Differences between aerobic respiration and fermentation DIFFERENCES Aerobic Respiration Fermentation The breakdown process of glucose is completed The breakdown process of glucose is incomplete in the presence of oxygen. without oxygen or in limited oxygen conditions. Occurs in cytoplasm and mitochondrion. Occurs in cytoplasm. Produces water. Does not produce water. Glucose is oxidised completely into carbon Glucose is not oxidised completely into ethanol dioxide and water. and carbon dioxide or lactic acid. One molecule of glucose generates 2898 kJ of One molecule of glucose generates 210 kJ energy (alcoholic fermentation) or 150 kJ (lactic acid fermentation) of energy 7.3Formative Practice 1 State where the process of fermentation cellular respiration that takes place in the usually occurs. muscle cells of your legs. 2 Give three examples of microorganisms and 4 State the differences between aerobic food produced by the fermentation process. respiration and fermentation. 3 While helping your father to cut the grass at the farm, you come across a snake. Terrified, you run away from the snake. Explain the 7.3.5 121 BioT4(NC)-B7-EN New 6th.indd 121 11/13/2019 12:09:40 AM

    Summary CELLULAR RESPIRATION Production of energy through cellular respiration The main substrate Aerobic Respiration Anaerobic Respiration Fermentation in energy production is glucose The breakdown of glucose in the The incomplete breakdown of presence of oxygen to produce glucose in limited oxygen or no chemical energy oxygen Occurs in cytoplasm Occurs in mitochondrion (pyruvate oxidation) Carbon dioxide + water + energy Glucose Pyruvate • Alcohol fermentation • Lactic acid fermentation Self Reflection 11/13/2019 12:09:40 AM Have you mastered the following important concepts? • The necessit y of energy in metabolic processes • The main substrate in the production of energy • Types of cellular respiration • Energy production from glucose during aerobic respiration in cells • Word equation for aerobic respiration in cells • Factors that cause fermentation to occur in cells • Example of energy production from glucose during fermentation • Lactic acid fermentation and alcohol fermentation • Yeast fermentation process • Differences bet ween aerobic respiration and fermentation 122 BioT4(NC)-B7-EN New 6th.indd 122

    Summative Practice 7 CHAPTER 7 1 What are the uses of alcohol fermentation products? 2 Why do muscles carry out cellular respiration that produces lactic acid during vigorous training? 3 Why does cellular respiration in muscles that produce lactic acid supply less energy compared to aerobic respiration? 4 Explain why an individual usually feels tired faster compared with an athlete, when both of them are running together. 5 A 100-metre sprinter usually holds his breath while running compared with a long-distance runner. After running, the sprinter needs seven litres of oxygen to remove the lactic acid in his muscle cells. Explain this difference between the sprinter and the long-distance runner. 6 Photograph 1 shows the activities by two individuals, P and Q. P Q PHOTOGRAPH 1 (a) (i) Based on Photograph 1, identify the respiration that occurs in the muscles of individuals P and Q. (ii) State the products of respiration in P and Q. (b) During the 100-metre sprint on Sports Day, a pupil experienced muscle cramps and had to stop running. Explain why muscle cramps happen. (c) Paddy plants grown in waterlogged areas have tolerance to ethanol compared with other plants. (i) State the type of fermentation that occurs in paddy plant cells. (ii) Write the word equation for the fermentation process that occurs in the paddy plant cells. (iii) Suggest another cell that can carry out the fermentation process as in question c(ii). 123 BioT4(NC)-B7-EN New 6th.indd 123 11/13/2019 12:09:41 AM

    Essay Questions 7 (a) Explain why energy is required in metabolic processes. (b) Compare aerobic respiration with fermentation. (c) Microorganisms such as yeast and bacteria usually play an important role in the fermentation process to produce food. Explain why yoghurt can spoil if it is not kept in the refrigerator. Enrichment 8 A person who is not used to exercising will experience muscle cramps when doing vigorous exercise because of the accumulation of lactic acid in the cells. However, for high-performance athletes, such problems do not occur because their bodies have a high tolerance for lactic acid. In your opinion, how do high performance athletes overcome the problem of lactic acid accumulation? Give your reasoning. 9 Studies have shown that intake of sodium bicarbonate or baking powder (baking soda) can increase muscle efficiency during intense activities that involve muscle fermentation. Give your justification. 10 While conducting an experiment using yeast, Mei Ling found that if grape juice is kept with yeast in a covered container, the yeast will slowly break down the glucose in the grapes. However if the container does not contain any oxygen, the yeast will break down the glucose at a faster rate, and the alcohol content in the container will rise very fast. At the end of the experiment, Mei Ling found that the breakdown rate of glucose becomes slow again even though there are some grapes that have not been oxidised. Explain Mei Ling’s observation. 11 Susan tried to make bread using dry yeast bought from a shop. When she mixed the yeast with plain flour, she found that her bread did not rise after half an hour. Explain how you can help Susan solve her problem. Complete answers are available by scanning the QR code provided 124 11/13/2019 12:09:41 AM BioT4(NC)-B7-EN New 6th.indd 124

    THEME PHYSIOLOGY OF HUMANS 2 AND ANIMALS Chapter 8 Respiratory System in Humans This theme aims to and Animals provide an understanding of the physiological processes in humans and animals. This theme focuses on physiological processes, which are respiration, nutrition, sensitivity, excretion, movement, reproduction and growth as well as cell division. Chapter 9 Nutrition and the Human Digestive System Chapter 10 Transport in Humans and Animals Chapter 11 Immunity in Humans Chapter 12 Coordination and Response in Humans Chapter 13 Homeostasis and the Human Urinary System Chapter 14 Support and Movements in Humans and Animals Chapter 15 Sexual Reproduction, Development and Growth in Humans and Animals

    Vagina Treatments

      : Antifungal medications can treat yeast infections, and antibiotic drugs can treat bacterial infections. Antiviral medicines treat infections from the herpes virus. : A variety of methods can be used to remove vaginal warts, including freezing, chemicals, burning with a laser, or cautery. : A small plastic or rubber device is placed inside the vagina to keep in place prolapsing pelvic organs. : Exercising the pelvic muscles (as when stopping your urine stream) may improve or prevent vaginal prolapse and urinary incontinence. : The genital organs of women both inside and out respond to estrogen. Estrogen treatment may be useful to revitalize these structures in postmenopausal women. : In rare cases of vaginal or cervical cancer, surgery is required to remove the tumor. Surgery may also treat vaginal prolapse.


    CDC: "Trichomoniasis - CDC Fact Sheet" and "Bacterial Vaginosis - CDC Fact Sheet."

    Watch the video: Muscular System. part-1. definitionclassification. handwritten notes. muscles (February 2023).