Muscles names of locomotor system - Equine

Muscles of Hip Flexion
1. Iliopsoas
2. Tensor Fascia Latae
3. Rectus Femoris
4. Sartorius
5. Articularis Coxae
Muscles of Hip Extension
1. Gluteus Medialis (Middle Gluteal)
2. Superficial Gluteal
3. Semitendinosus
4. Semimembranosus
5. Biceps Femoris
6. Piriformis
7. Gracilis
8. Adductores (Adductor Magnus et Brevis and Longus
9. Quadratus Femoris
10. Gluteus Profundus
Muscles of Hip Abduction
1. Gluteus Medialis
2. Gluteus Profundus
Muscles of Hip Adduction
1. Adductores (Adductor Magnus et Brevis and Longus)
Muscles of Lateral Rotation of the Hip
1. Obturator Internus
2. Gemelli
3. Quadratus Femoris
4. Obturator Externus

Muscles of Adduction of the Thigh
1. Gracilis
2. Pectineus
Muscles of Abduction of the Thigh
1. Abductor Cruris Caudalis
2. Biceps Femoris

Muscles of Flexion of the Stifle
1. Gastrocnemius
2. Biceps Femoris
3. Semimembranosus
4. Sartorius (caudal part)
5. Abductor Cruris Caudalis
6. Flexor Digitorum Superficialis
7. Popliteus
8. Semitendinosus
Muscles of Extension of the Stifle
1. Sartorius (cranial part)
2. Biceps Femoris
3. Quadriceps Femoris
A. Rectus Femoris
B. Vastus Lateralis
C. Vastus Intermedius
D. Vastus Medialis
4. Articularis Genus

Muscles of Extension of the Hock
1. Gracilis

Muscles of Flexion of the Tarsus
1. Peroneus Longus
2. Tibialis Cranialis
3. Extensor Digitorum Longus
4. Peroneus Brevis
Muscles of Extension of the Tarsus
1. Gastrocnemius
2. Flexor Digitorum Superficialis
3. Tibialis Caudalis
4. Semitendinosus

Muscles of Flexion of the Caudal Digits
1. Flexor Digitorum Longus
2. Flexor Digitorum Superficialis
3. Flexor Digitorum Profundus
Muscles of Extension of the Caudal Digits
1. Extensor Digitorum Longus
2. Extensor Digiti 1
3. Extensor Digitorum Lateralis (digit 5)
4. Extensor Digitorum Brevis

Muscles of Lateral Rotation of the Caudal Paw
1. Tibialis Cranialis
2. Tibialis Caudalis
Muscles of Medial Rotation of the Caudal Paw
1. Peroneus Longus

Muscles of Vertebral Fixation Lumbar Region
1. Iliopsoas
2. Quadratus Lumborum
Muscles of Flexion of the Lumbar Vertebra
1. Iliopsoas

Muscles of Adduction of the Shoulder
1. Subscapularis
2. Coracobrachialis
3. Pectoralis Superficialis
Muscles of Flexion of the Shoulder
1. Latissimus Dorsi
2. Pectoralis Superficialis
3. Pectoralis Profundus
4. Infraspinatus
5. Teres Minor
6. Deltoideus
7. Teres Major
8. Triceps Brachii
9. Romboideus
10. Serratus Ventralis
11.Subscapularis
Muscles of Extension of the Shoulder
1. Trapezius
2. Cleidocervicalis
3. Pectoralis Superficialis
4. Pectoralis Profundus
5. Supraspinatus
6. Subscapularis
7. Biceps Brachii
8. Coracobrachialis
9. Omotransversarius
10. Serratus Ventralis
11. Coracobrachialis
12. Romboideus
13. Infraspinatus
Muscles of Elevation of the Shoulder
1. Trapezius
2. Rhomboideus

Muscles of Abduction of the Humerus
1. Infraspinatus
Muscles of Lateral Rotation of the Humerus
1. Infraspinatus
Muscles of Elevation of the Humerus
1. Deltoideus
Muscles of Extension of the Humerus
1. Teres Major

Muscles of Flexion of the Elbow
1. Biceps Brachii
2. Brachialis
3. Extensor Carpi Radialis
4. Supinator
5. Pronator Teres
Muscles of Extension of the Elbow
1. Triceps Brachii
2. Tensor Fasciae Antibrachii
3. Extensor Carpi Ulnaris
4. Anconeus

Muscles of Cranial Limb Medial Rotation
1. Pronator Teres

Muscles of Lateral Rotation of the Forearm
1. Extensor Carpi Ulnaris
Muscles of Dorsal Lateral Rotation of the Radius
1. Brachioradialis

Muscles of Abduction ot the Carpal Joint
1. Flexor Carpi Ulnaris
Muscles of Flexion of the Carpal Joint
1. Flexor Carpi Radialis
2. Flexor Carpi Ulnaris
3. Flexor Digitorum Profundus
4. Interflexorius
5. Flexor Digitorum Brevis
Muscles of Extension of the Carpal Joint
1. Extensor Carpi Radialis
2. Extensor Digitorum Communis
3. Extensor Carpi Ulnaris
Muscles of Pronation of the Carpal Joint
1. Pronator Quadratus

Muscles of Supination of the Cranial Paw
1. Supinator
Muscles of Flexion of the Cranial Paw
1. Flexor Carpi Ulnaris

Muscles of Abduction of the Digits
1. Abductor Pollicis Longus
2. Abductor Digiti 5
Muscles of Adduction of the Digits
1. Adductor Digiti 5
2. Adductor Digiti 2
3. Extensor Digiti 1 and 2
Muscles of Flexion of the Digits
1. Abductor Digiti Brevis
2. Flexor Digiti 1 Brevis
3. Flexor Digitorum Superficialis
Muscles of Extension of the Digits
1. Extensor Digitorum Lateralis
2. Extensor Digiti 1 and 2
3. Abductor Pollicis Longus

Muscles of Neck Extension
1. Splenius
2. Longissimus Cervicis
3. Semispinalis Cervicis
4. Semispinalis Capitis
5. Longissimus Capitis
6. Obliquus Capitis Cranialis
Muscles of Flexion of the Neck
1. Scalenus
2. Longus Capitis
3. Longus Colli
4. Rectus Capitis Ventralis
5. Rectus Capitis Lateralis
Muscles of Fixation of the Neck
1. Splenius
2. Cleidocervicalis
3. Oblique Capitis Cauda1lis
Muscles of Lateral Flexion of the Neck
1. Splenius
2. Scalenus
3. Brachiocephalicus
4. Sternocephalicus
Muscles of Rotation of Neck
1. Oblique Capitis Caudalis
2. Longissimus Capitis

Muscles of Expiration
1. Iliocostalis
2. Serratus Dorsalis Caudilis
3. Intercostalis Externi
4. Intercartilaginei Externi
5. Intercostalis Interni
6. Subcostalis
7. Intercartilaginei Interni
8. Retractor Costa
10.Transversus Thoracis
Muscles of Inspiration
1. Levatores Costarum
2. Rectus Thoracis

Muscles of Fixation of the Thorax
1. Semispinalis Thoracis
2. Multifidus
3. Rotatores Longi
4. Rotatores Brevis
5. Interspinalis

Muscles of Abdominal Compression, Support of the Viscera, Expiration, Urination, Defecation andParturition
1. Obliquus Internus
2. Obliquus Abdominus
3. Transversus Abdominus
4. Rectus Abdominus

Muscles of Abdominal Flexion
1. Rectus Abdominus

Muscles of Skin Shaking and Increase Heat Production
1. Cutaneous Trunci

Muscles of Fixation of the Vertebral Column
1. Longissimus Thoracis
2. Iliocostalis
3. Multifidus
Muscles of Extension of the Vertebral Column Cranially
1. Longissimus Thoracis
Muscles of Extension of the Vertebral Column Caudally
1. Longissimus Thoracis
Muscles of Lumbar Extension
1. Longissimus Lumborum

Muscles of Fixation of the Lumbar Region
1. Iliocostalis
2. Multifidus
3. Interspinales
Muscles of Lateral Flexion of the Lumbar Region
1. Iliocostalis
2. Longissimus Lumborum

Muscles of Extension of the Tail
1. Sacro Caudalis Dorsalis Lateralis
2. Sarco Caudalis Dorsalis Medialis
Muscles of Lateral Flexion of the Tail
1. Sacro Caudalis Dorsalis Lateralis
2. Sacro Caudalis Dorsalis Medialis
3. Intertransversarius Dorsalis Caudalis
4. Intertransversarius Ventralis Caudalis
Muscles of Flexion of the Tail
1. Sacro Caudalis
2. Sacro Caudalis Ventralis Lateralis
3. Sacro Caudalis Ventralis Medialis

Muscles of Unilateral-Lateral Flexion
1. Coccygeus
2. Levator Ani

Muscles of Mastication Elevation of Mandible
1. Masseter
2. Temporalis
3. Pterygoideus Lateralis
4. Pterygoideus Medialis
Muscles of Mastication Depression of Mandible
1. Digastric

Spinal Cord Gross Anatomy - image

The spinal cord is a long cylinder of nervous tissue with subtle cervical and lumbar (lumbosacral) enlargements. The enlarged segments contribute to the brachial and lumbosacral plexuses. In the above image, showing a brain and spinal cord from a neonatal pig, the spinal cord and spinal roots are enveloped by dura mater.

The spinal cord is divided into spinal cord segments. Each segment gives rise to paired spinal nerves. Dorsal and ventral spinal roots arise as a series of rootlets. A spinal ganglion is present distally on each dorsal root. The canine spinal cord has 8 cervical, 13 thoracic, 7 lumbar, 3 sacral and 5 caudal segments. The following table compares species.

Spinal cord Segments and spinal Roots


Dural mater (dm) is reflected to expose segments and roots in a length of equine spinal cord. The arrow points to the dorsal median sulcus. The orange pic (asterisk) marks the dorsolateral sulcus, where dorsal roots enter the spinal cord. Each spinal cord segment gives rise to right and left dorsal and ventral spinal roots. Each spinal root is composed of rootlets (r). The dorsal root (DR) and the ventral root (VR) unite to form a spinal nerve (SN). A spinal ganglion (SG) is located distally on each dorsal root. Colored pics mark: spinal ganglia (red), the separation between dorsal and ventral roots (black), and the location of the denticulate ligament. The specimen rests on white cardboard.

Spinal cord segments in different species (for reference purposes):
Dog: 8 cervical; 13 thoracic; 7 lumbar; 3 sacral; & 5 caudal = 36 total
Cat: 8 cervical; 13 thoracic; 7 lumbar; 3 sacral; & 5 caudal = 36 total
Bovine: 8 cervical; 13 thoracic; 6 lumbar; 5 sacral; & 5 caudal = 37 total
Horse: 8 cervical; 18 thoracic; 6 lumbar; 5 sacral; & 5 caudal = 42 total
Swine: 8 cervical; 15/14 thoracic; 6/7 lumbar; 4 sacral; & 5 caudal = 38 total
Human: 8 cervical; 12 thoracic; 5 lumbar; 5 sacral; & 1 coccygeal = 31 total

The spinal cord and spinal roots are enveloped by meninges and housed within the vertebral canal. The epidural space, situated between the wall of the vertebral canal and the spinal dura mater, contains a variable amount of fat. Within dura mater, the spinal cord is suspended by bilateral denticulate ligaments and surrounded by subarachnoid space filled with cerebrospinal fluid. Dorsal and ventral spinal roots unite to form spinal nerves which exit the vertebral canal at intervertebral foramina. An intervertebral foramen is formed by adjacent vertebrae and by the intervertebral disc joining the vertebrae.

The spinal cord and spinal roots are enveloped by meninges and housed within the vertebral canal. The epidural space, situated between the wall of the vertebral canal and the spinal dura mater, contains a variable amount of fat. Within dura mater, the spinal cord is suspended by bilateral denticulate ligaments and surrounded by subarachnoid space filled with cerebrospinal fluid. Dorsal and ventral spinal roots unite to form spinal nerves which exit the vertebral canal at intervertebral foramina. An intervertebral foramen is formed by adjacent vertebrae and by the intervertebral disc joining the vertebrae.

As a result of differential growth of the spinal cord and vertebral column, most spinal cord segments are positioned cranial to their nominally corresponding vertebrae. However, spinal segment length is variable along the spinal cord in our domestic mammals. Segments become progressively shorter from the C3 to T2. Then they elongate so that segments at the thoracolumbar junction are within nominally corresponding vertebrae. Thereafter, segments progressively shorten until the cord terminates in a terminal filament of glia. (The term "conus medullaris" refers to the cone-shaped cord region between the lumbosacral enlargement and the glial filament.)

Since spinal nerves exit the vertebral canal at nominally corresponding intervertebral foramina, spinal roots must elongate when spinal cord segments are displaced cranially. The term cauda equina (horse tail) refers to caudally streaming spinal roots running to intervertebral foramina in the sacrum and tail. Damage to the cauda equina affects pelvic viscera and the tail. Cauda equina epidural anesthesia (putting anesthetic into the epidural space to block conduction in spinal roots) is a common obstetrical procedures in cattle.

Because vertebrae can be palpated and visualized in ordinary radiographs, unlike spinal segments, it is clinically useful to know locations of spinal cord segments relative to vertebrae. Typically (for most dogs) the cervical enlargement is centered at the C6-7 intervertebral disc; spinal segments of the thoracolumbar junction are within nominally corresponding vertebrae; the sacral segments are within vertebra L5; and the functional spinal cord terminates at the L6-7 vertebral junction. (Termination is about one vertebra further caudally in small dogs, less than 7 kg.)

Spinal cord Within Vertebral Canal



The following drawing depicts a spinal cord segment within a lumbar vertebra, at the level of an intervertebral disc (nucleus pulposus surrounded by annulus fibrosus). spinal nerves are present bilaterally at intervertebral foramina, dorsal to the disc. An epidural space, containing fat, is evident external to spinal dura mater (blue). The latter is shown surrounding roots on the left; it is removed on the right side. Bilaterally, dorsal and ventral spinal roots (green) unite to form a spinal nerve (yellow) which soon branches. Bilateral thickenings of pia mater (purple), called denticulate ligaments, suspend the spinal cord within the dura mater.

spinal cord In Situ



Left: Cervical transection through an intervertebral disc (nuchal ligament at the top). The spinal cord, surrounded by meninges, is evident within the vertebral canal. Internal vertebral venous sinus is marked by asterisks. (Vertebral a. & v. are visible bilaterally.)
Right: Thoracic vertebra transection. The spinal cord is surrounded by meninges within the vertebral canal. Internal vertebral venous sinus is marked by asterisks.

Canine spinal Cord



Cranial and caudal halves of a canine vertebral column are illustrated, after a laminectomy to expose the spinal cord. Spinal cord segments are labeled, and locations of vertebral bodies separated by intervertebral discs are shown to the right. Dura mater (blue) has been removed except along the right side. The illustrated position relationship of spinal cord segments to vertebrae represents the most common relationship for medium and large dogs (typical variation is half a vertebral length cranial or caudal to that shown). In small dogs (under 7kg) spinal cord segments are positioned more caudally than is shown.

Canine spinal cord — Cranial Half


The cranial half of a canine vertebral column has been drawn after a laminectomy to expose the spinal cord. spinal cord segments are labeled and locations of vertebral bodies separated by intervertebral discs are labeled to the right.
Dura mater (blue) has been removed except along the right side. Dura mater envelops spinal roots including spinal ganglia.
Notice that spinal segments vary in length and that spinal roots must elongate to reach intervertebral foramina where segments are shifted cranially. In the cervical region, notice that the spinal root of the accessory cranial nerve (Accessory r., tan) emerges laterally, between dorsal and ventral roots. The C1 spinal nerve (N.1C, yellow) exits from a lateral foramen, rather than an intervertebral foramen like other spinal nerves. The C8 spinal segment appears to be "extra" (it lacks a nominally corresponding vertebra). Thus, caudal to the cervical region, spinal nerves exit through intervertebral foramina located at caudal margins of nominally corresponding vertebrae.
The C3 segment is the longest. Thereafter, segments progressively shorten in length. After the T2 segment, segments progressively lengthen. The cervical enlargement (C6, 7, 8, & T1) which innervates the thoracic limb (brachial plexus) is centered approximately at the C6-C7 intervertebral disc.

Canine spinal cord — Caudal Half


The cranial half of a canine vertebral column has been drawn after a laminectomy to expose the spinal cord. spinal cord segments are labeled and locations of vertebral bodies separated by intervertebral discs are labeled to the right.
Dura mater (blue) has been removed except along the right side. Dura mater envelops spinal roots including spinal ganglia.
Notice that thoracolumbar spinal segments are long and located within nominally corresponding vertebrae. Thereafter, segments progressively shorten in length and spinal roots elongate as segments shift position cranial to nominally corresponding vertebrae. Sacral and caudal roots streaming caudally are referred to as the cauda equina. Notice that the cauda equina is initially intrathecal (within the main cylinder of spinal dura mater); thereafter, the roots are enveloped by dural sheaths in the epidural space.
The term conus medullaris refers to the cone-shaped region of spinal cord caudal to the lumbosacral enlargement (L4 — S1). The cord terminates approximately at the L6-L7 intervertebral disc. Thereafter a terminal filament of glial tissue continues for some distance. The term caudal ligament refers to the terminal filament enveloped by a dural sheath.

Canine spinal cord Termination


Illustration of a canine spinal cord termination. A laminectomy was performed and dura mater has been reflected to expose spinal cord segments and spinal roots. Dorsal roots are cut on the left side to expose the denticulate ligament (purple). Notice the termination of the denticulate ligament; the cauda equina; and the terminal filament (filum terminale), a glial continuation persisting beyond the functional end of the spinal cord. The illustrated position of the spinal cord termination at the L6-L7 intervertebral disc represents the most common relationship for medium and large dogs (varying plus or minus a half vertebra). In small dogs (under 7 kg) the typical position is one vertebra caudal to that shown.

Spinal Cord—Vertebrae Relationships



It is clinically useful to know the approximate locations of spinal cord segments relative to palpable, radiographically visible vertebrae. One learning strategy is to remember the following four relationships and then interpolate other position relationships as necessary. (The illustrated relationships are the most common for medium and large dogs ( half vertebra). In small dogs the position is one vertebra caudal to that shown.)
A. The cervical enlargement (brachial plexus segments) are centered at the C6-C7 intervertebral disc.
B. At the thoraco-lumbar junction, segments are positioned within nominally corresponding vertebrae.
C. The three sacral segments are located within the L5 vertebra.
D. The spinal cord terminates at the L6-L7 intervertebral disc

Importance of Vitamins & its deficiency in animals

Vitaminsare organic substances that must be provided in small quantities by the environment (usually the diet) and are generally classified in two categories: the water-soluble and the fat-soluble vitamins. These small organic molecules cannot be made in adequate amounts by the body but are required for normal metabolism.

Water Soluble Vitamins

Water-soluble vitamins consist of members of the vitamin B complex and vitamin C. They are generally found together in the same foods with the exception of B12 which is present only in meat and dairy foods. The others are found in whole grain cereals, legumes, leafy green vegetables, and fruits. The water-soluble vitamins generally function to assist the activity of important enzymes such as those involved in the production of energy from carbohydrates and fats. They are often referred to as "cofactors". Other roles may be defined with further research. The water-soluble vitamins are not stored to a great extent in the body so frequent consumption is necessary. When present in excess of the body's needs, they are excreted in the urine. Because they are readily excreted, they are generally non-toxic, although symptoms have been reported in some individuals taking megadoses of niacin, vitamin C or pyridoxine. The lack of water soluable vitamins most greatly affects tissues that are growing or metabolizing rapidly such as skin, blood, the digestive tract and nervous system. These molecules present in fruit, vegetables and grains are all unstable in the presence of heat so that processing and cooking methods can greatly affect the amount of vitamin actually available in food.

Vitamin B Complex – The vitamin B complex is traditionally made up of 10 members (listed below) that differ in their biological actions, although many participate in energy production from carbohydrates and fats. They were grouped together into a single class because they were initially isolated from the same sources, liver and yeast.

Thiamine (Vitamin B1) is important for energy metabolism and in the initiation of nerve impulses. A deficiency of thiamine causes a condition known as beriberi. In certain parts of the world where the diet consists largely of polished rice, this condition is frequently seen. In these countries, a deficiency in mothers can cause a deficiency in infants and may lead to death. In the US, thiamine deficiency is most commonly seen in alcoholics, although it can occur in the presence of several diseases. Pregnancy increases thiamine requirements slightly and when a pregnancy is associated with a prolonged period of vomiting and/or poor food intake, thiamine deficiency may result.

The major symptoms of the deficiency are related to the nervous system (i.e. sensory disturbances, muscle weakness, impaired memory) and the heart (i.e. shortness of breath, palpitations, and heart failure). Wernicke’s syndrome is a serious complication of alcoholism and thiamine deficiency that may manifest as impaired muscle coordination, impaired ability to move the eyes, and marked confusion. It may lead to Korsakoff’s psychosis, a chronic disorder in which memory and learning are impaired.

Thiamine is used to treat thiamine deficiency. There are many unproven uses of thiamine including a treatment for poor appetite, canker sores, motion sickness, poor memory, fatigue and as an insect repellant. The RDA for women over 18 years is 1.1 mg; for pregnant women, 1.4 mg; for lactating women, 1.5 mg; and for men over 14 years, 1.2 mg

Riboflavin (Vitamin B2) is important in promoting the release of energy from carbohydrates, fats and proteins. It also aids in maintaining the integrity of red blood cells. Riboflavin deficiency can occur most frequently in people with long-standing infections, liver disease, and alcoholism. A sore throat and sores at the corners of the mouth are generally the first symptoms of a deficiency. This can be followed by a swollen tongue, seborrheic dermatitis, anemia and impaired nerve function. These manifestations are commonly seen in other diseases, including many vitamin deficiencies. The RDA for women over 18 years is 1 mg; for pregnant women, 1.4 mg; for lactating women, 1.6 mg, and for men over 14 years, 1.3 mg.

A deficit of cellular energy metabolism may play a role in migraine headaches. A recent study indicated that high-dose (400 mg/day) riboflavin was effective in decreasing the frequency of migraines. Further studies are needed to confirm this effect. High dose riboflavin can cause a yellow-orange fluorescence or discoloration of the urine.


Nicotinic acid (Niacin, Vitamin B3) is important for the release of energy from carbohydrates and fats, the metabolism of proteins, making certain hormones, and assisting in the formation of red blood cells. Niacin deficiency causes pellagra, a condition that affects the skin (dermatitis), GI tract (i.e. diarrhea, nausea, vomiting and swollen tongue) and nervous system. (i.e. headache, depression, impaired memory, hallucinations and dementia). Frequent causes of a deficiency include a poor diet, isoniazid therapy (used in the treatment of tuberculosis) and carcinoid tumors. Rarely a deficiency can occur in the presence of hyperthyroidism, diabetes mellitus, cirrhosis, pregnancy or lactation.

Dietary niacin and niacin formed within the body from the amino acid tryptophan are converted to niacinamide. Niacinamide (nicotinamide) is the biologically active form of niacin and it may be preferred as a supplement because it lacks the flushing effects of niacin. The RDA for women over 14 years is 14 mg; for pregnant women, 18 mg; for lactating women, 17 mg; and for men over 14 years, 16 mg.

Niacin is used for the treatment of niacin deficiency but at large doses is also used to treat high cholesterol and triglycerides. High doses should only be taken under the supervision of a physician because there is a risk of developing serious side effects such as liver dysfunction. There are also several medical conditions that may be worsened by its use at the high, therapeutic doses. It can cause the release of histamine resulting in increased gastric acid, therefore it is generally not used in the presence of an active peptic ulcer. Large amounts can also decrease uric acid excretion, possibly precipitating a gout attack in people predisposed to this condition, and it can impair glucose tolerance, interfering with blood sugar control in diabetics. In the treatment of high cholesterol the simultaneous use of niacin with drugs that inhibit cholesterol formation, known as the HMG-CoA reductase inhibitors (i.e. Lipitor®, Baycol®, Mevacor®, Zocor® and Pravachol®) increases the occurrence of serious muscle disorders.

Due to common side effects (flushing, nausea, dizziness, itching, low blood pressure), many people do not tolerate high doses of niacin, even though some may lessen in intensity with continued usage.


Pyridoxine (Vitamin B6) is necessary for the proper function of over 60 enzymes that participate in amino acid metabolism. It is also involved in carbohydrate and fat metabolism. A deficiency in adults mainly affects the skin (seborrhea-like lesions around the eyes, nose and mouth), mucous membranes, peripheral nerves and blood forming system. Convulsive seizures may also occur. Deficiencies can manifest in people with kidney disease, cirrhosis, alcoholism, impaired gastrointestinal absorption (malabsorption), congestive heart failure and hyperthyroidism.

The RDA for pyridoxine in women from 19-50 years of age is 1.3 mg; women over 50 years, 1.5 mg; for pregnant women, 1.9 mg; for lactating women, 2 mg; for men 14 to 50 years of age, 1.3 mg; and for men over 50 years, 1.7 mg. Prolonged doses in excess of 200 mg. per day have been associated with neurotoxicity. Pyridoxine may be effective in lowering high levels of homocysteine, a risk factor for heart disease, decreasing the symptoms of premenstrual syndrome, as an adjunct to other treatments for improving behavior in autism, and for reversing some of the side effects of flurouracil in cancer patients. It is also used in treating some metabolic disorders.

Several drugs can increase the pyridoxine requirement, such as hydralazine, isoniazid and oral contraceptives. Simultaneous use of pyridoxine with amiodarone can increase the risk of drug-induced sensitivity to sunlight, and pyridoxine can decrease the effects of phenytoin and phenobarbital.


Pantothenic acid (Vitamin B5) is the precursor to coenzyme A that is vital for the metabolism of carbohydrates, the synthesis and degradation of fats, the synthesis of sterols and the resultant steroid hormones, and the synthesis of many other important compounds. A deficiency has not been seen in humans on a normal diet because it is so widely distributed in foods, however it is often included in multivitamin preparations.

There is insufficient information to establish RDAs for pantothenic acid. The Committee on Dietary Allowances provides provisional recommendations for adults of 4 to 7 mg. per day.

Folic acid (Vitamin B9) plays a major role in cellular metabolism including the synthesis of some of the components of DNA. It is necessary for normal red blood cell formation and adequate intake can reduce damage to DNA.

Folic acid deficiency is a common complication of diseases of the small intestine that interfere with the absorption of folic acid from food and the recycling of folic acid from the liver back to the intestines. Alcoholism can result in folic acid deficiency. Folic acid activity can also be reduced by several drugs including large doses of nonsteroidal anti-inflammatory drugs (NSAIDs), methotrexate, trimethoprim, cholestyramine, isoniazid, and triamterene. The simultaneous ingestion of folic acid supplements may, in theory, interfere with the effectiveness of methotrexate cancer treatments, however their combined use in the treatment of rheumatoid arthritis and psoriasis has resulted in lessened side effects from methotrexate.

Although the anemia that results from folic acid deficiency is not distinguishable than that resulting from B12 deficiency, folic acid deficiency is rarely associated with neurological abnormalities (see Vitamin B12). Excessive doses of folic acid may mask the anemia that results from B12 deficiency, preventing diagnosis of the deficiency and allowing progression of neurological damage.

Adequate folic acid intake is associated with a reduced risk of neural tube birth defects. It is recommended that all women of childbearing age consume at least 400 micrograms of folic acid each day. Folic acid supplements are also used to lower elevated homocysteine levels, a known risk factor for heart disease. Recent studies have suggested that folic acid supplements may be effective in lowering the risk of colon cancer. Topical folic acid formulations are used for gingival hyperplasia that result from phenytoin therapy and for gingivitis associated with pregnancy.

The RDA for folic acid for adults over 13 years, 400 micrograms; for pregnant women, 600 micrograms; and lactating women, 500 micrograms.

Vitamin B12 (Cyanocobalamin) is important for the proper functioning of many enzymes involved in carbohydrate, fat and protein metabolism, synthesis of the insulating sheath around nerve cells, cell reproduction, normal growth and red blood cell formation. It is essential for proper folic acid utilization. A deficiency results in anemia, gastrointestinal lesions and nerve damage. Many drugs can interfere with the absorption of vitamin B12 including drugs commonly used to treat ulcers (such as cimetidine, omeprazole), and drugs used to treat seizures (such as phenytoin and phenobarbital).

A protein called intrinsic factor is secreted by the stomach and is required for vitamin B12 absorption from the lower part of the small intestine. Signs of B12 deficiency often occur in the presence of adequate B12 intake, but result from impaired absorption. Conditions that are associated with this include some gastric surgeries, pancreatic disorders, bacterial overgrowth or intestinal parasites, and damage to the intestinal cells.

The RDA for vitamin B12 for adults is 2.4 micrograms; for pregnant women, 2.6 micrograms; and for lactating women, 2.8 micrograms. Approximately 10 to 30% of people over 50 years of age have difficulty absorbing food-bound vitamin B12, so they should eat foods fortified with the vitamin or take a supplement.

Vitamin B12 and folic acid have a close relationship. A deficiency in either one results in abnormal synthesis of DNA in any cell in which cell division is taking place. Tissues such as the blood forming system are most severely affected, therefore an early sign of deficiency of either vitamin is a type of anemia termed megaloblastic anemia.


Choline is traditionally not a vitamin, however it was identified as part of the vitamin B complex and has several important functions. Choline is a component of many biological membranes and fat transport molecules in the blood. It is able to stimulate the removal of excess fat from the liver. Choline serves as the precursor to many substances including a the transmitter of the parasympathetic nervous system, acetylcholine. Some athletes use choline to delay muscle fatigue because acetylcholine is involved in muscle contraction, but this effect has not been proven. A deficiency is uncommon except among people receiving long-term IV nutrition. It is added to infant formulas to approximate the amount found in human milk.

The Daily Reference Intake (DRI) is 550 mg for adult males and lactating females; 425 mg for adult females; and 450 mg for pregnant females. Oral choline supplements have not been proven to be effective in treating memory loss, Alzheimer’s disease, dementia and schizophrenia.

Inositol is an important part of cell membranes and is part of a signaling mechanism that transmits information from the outside to the inside of cells. Some evidence suggests it participates in the movement of fat out of the liver and intestinal cells, and that it may reverse desensitization of serotonin receptors, however this remains to be confirmed. Although it may be effective in treating panic disorders, depression and obsessive-compulsive disorders, these uses remain to be verified.

A dietary need for inositol has not been established, probably due to its production by gut bacteria, the existence of tissue stores following absorption from food, and possible synthesis in some organs. It may be added to infant formulas to approximate the content of human milk.


Biotin has an important role in carbohydrate and fat metabolism. It can be synthesized by gut bacteria and recycled. A deficiency rarely occurs in humans. If raw egg whites are consumed in large quantities, a biotin deficiency can occur. Signs of a deficiency include dermatitis, muscle pain, loss of appetite, slight anemia, an inflamed tongue, and weakness. There is no RDA for biotin.


Vitamin C (Ascorbic Acid) has many important functions in the body. It is a powerful antioxidant, protecting against oxidative damage to DNA, membrane lipids and proteins. It is involved in the synthesis of numerous substances such as collagen, certain hormones and transmitters of the nervous system, lipids and proteins. It is necessary for proper immune function, a fact that has led many to use vitamin C to prevent or treat colds, although this has not been supported by current studies. It may, however, shorten or reduce the severity of a cold.

Vitamin C deficiency causes scurvy that is characterized by capillary fragility resulting in bruising and hemorrhaging, inflammation of the gums, loosening of the teeth, anemia and general debility that can lead to death. The RDA for adults 15 years and older is 60 mg; for pregnant women, 70 mg; and for lactating women in the first six months, 95 mg decreasing to 90 mg for the second six months. There may be increased vitamin C requirements for people taking estrogens, oral contraceptives, barbiturates, tetracyclines, aspirin and for cigarette smokers. Large doses of vitamin C can interfere with many laboratory tests. Side effects from large doses include nausea, vomiting, heartburn, abdominal cramps, headache and diarrhea.

Diets containing 200mg or more of vitamin C from fruits and vegetables are associated with a lower cancer risk, particularly for cancers of the colon, lung, mouth, esophagus and stomach. The consumption of dietary supplements have not been shown to have the same effect. It may block the formation of N-nitrosamines, cancer-causing agents from certain foods. Ascorbic acid alone does not appear to prevent heart disease, however the combined use with vitamin E may reduce the risk of heart disease

Fat-Soluble Vitamins

Fat soluble vitamins are found in meats, liver, dairy, egg yolks, vegetable seed oils, and leafy green vegetables. Some foods such as milk and margarine are artificially fortified with vitamins A and D. These vitamins are metabolized along with fat in the body and require fat for absorption in the gut. The fat-soluble vitamins may be stored in large amounts, and this gives them the potential to cause toxicity if consumed in high amounts. Deficiencies are rare in adults but may be seen in children. Megadosing of fat soluable vitamins, except where indicated by a medical professional, is potentially dangerous and should be avoided. Two of the fat-soluble vitamins, A and D, have hormone like actions, causing specific cells to increase or decrease the expression of certain genes.

Vitamin A (retinol) plays a vital role in the functioning of the retina, growth and maturation of the cells lining the inner and outer surfaces of the body (the epithelial cells), growth of bone, reproduction and embryonic development. Several compounds have vitamin A activity and they are referred to as retinoids. They function with certain carotenoids to protect against the development of certain cancers and to enhance immune function. Carotenoids are substances that are consumed in the diet, some of which are converted to vitamin A. They may also have antioxidant activity.

Deficiency

Vitamin A deficiency causes night blindness, a condition in which vision is impaired in dim light. Dryness and ulceration of the eyes, skin eruptions and dryness, abnormal cells of the mucous membranes, urinary stones, and impaired taste and smell also characterize the deficiency. Many children in developing countries have irreversible blindness resulting from vitamin A deficiency. In the US, it occurs more commonly in chronic diseases that affect fat absorption such as pancreatic insufficiency and portal cirrhosis, or following removal of a portion of the stomach. Vitamin A is stored in several sites in the body, so when a deficiency occurs, supplements must be given long enough for these stores to be replenished

Toxicity

Toxicity from excessive doses of vitamin A can also occur. Chronic ingestion of toxic doses results in symptoms progressing from mild dermatitis to hemorrhage, increased intracranial pressure, and liver damage. Pregnant women that ingest quantities above that which is recommended can cause the development of fetal malformations. Women that have been treated with synthetic retinoids that accumulate in fat may require several drug free years or longer before the increased risk to the fetus subsides.

Dietary Sources & RDA

The best sources of vitamn A are highly pigmented vegetables and fortified margarine. A normal diet contains both carotenoids and vitamin A, so calculations of dietary vitamin A combines both sources and is often measured in retinol equivalents (REs). The RDA for males 11 years and older is 1000 RE (3300 units); for females 11 years and older is 800 RE (2700 units); for pregnant females, 800 RE (2700 units); for lactating females during the first 6 months, 1300 RE (4300 units) and during the second 6 months, 1200 RE (4000 units). Topical forms of vitamin A are used in the treatment of several conditions including acne, psoriasis and to reverse the damage resulting from sun exposure.

Vitamin E (tocopherol) has many actions in the body. It mainly acts as an antioxidant of lipids, protecting cell membranes and preventing damage to membrane associated enzymes. The manifestation of a deficiency is rare in the US because it is present in many foods and there are large total body stores. Vitamin E is present as alpha, beta and gamma tocopherols. Supplements may contain the alpha tocopherol that is either in the "d" form or a combination of the "d" and "l" forms. The "d" form is more active than the "l" form but when comparing supplements, an equivalent number of international units (IU) indicate equivalent activity. Less information is available about the action of the beta and gamma tocopherols, but they appear to have different antioxidant effects. A supplement that contains all forms may provide the greatest benefits. There are several conditions in which vitamin E supplementation may have a beneficial effect but these remain to be proven by long-term studies. It may slow the progression of Alzheimer’s disease, prevent heart disease, improve immune function in the elderly, reduce the risk of cataracts and decrease the pain associated with arthritis.

Deficiency

There is no known syndrome associated with vitamin E deficiency in adults but in premature infants, anemia may be seen.Vitamin E supplements are sometimes given to people at a risk for developing a deficiency such as children with cystic fibrosis, cholestatic liver disease or other disorders of gastrointestinal absorption

Toxicity

A high dietary intake may decrease the risk of some cancers, but oral supplements do not appear to have the same effect. High doses of supplements interfere with blood clotting and may increase the risk of bleeding in people with bleeding tendencies or those on anticoagulants (blood thinners). Megadose intake may induce blurred vision or headaches.

Dietary Sources & RDA

The major sources for this vitamin are vegatable seed oils. The RDA for d-alpha tocopherol for males 11 years and older is 15 IU; for females 11 years and older, 12 IU; for pregnant females, 15 IU; for lactating women during the first 6 months, 18 IU and during the second 6 months, 16.5 IU.

Vitamin D (calciferol) acts as a hormone that promotes formation of bone by increasing the blood levels of calcium and phosphorus. It is synthesized by the skin upon exposure to sunlight. Receptors for vitamin D are found throughout the body and it is thought that they mediate a variety of activities, some of which are unrelated to calcium metabolism.

The precursor for vitamin D3 (cholecalciferol) is a product of cholesterol metabolism. The precursor for vitamin D2 (ergocalciferol) is found in plants. In humans, vitamins D2 and D3 appear to have the same activity and they are referred to collectively as vitamin D. Vitamin D is activated by the liver and kidney (although several other organs can participate in its activation) to calcitriol. The ability and necessity of maintaining tight control of calcium levels in the blood is served by interaction of many components including vitamin D and parathyroid hormone (PTH). When calcium levels decrease, vitamin D stimulates increased intestinal absorption of calcium and phosphorus, increased release of calcium from the bone, and decreased excretion of calcium in the urine.

Deficiency

Without vitamin D, there is insufficient absorption of calcium and phosphorus, and the blood levels of calcium are maintained at the expense of bone break down. In children, impaired bone and cartilage formation leads to rickets, characterized by skeletal deformities. In adults, osteomalacia can occur in which impaired bone mineralization can lead to bone pain and deformity in advanced cases

Vitamin D supplements are used in the treatment of nutritional rickets. Supplements may also be used in the treatment of conditions associated with poor absorption such as diarrhea and biliary obstruction, and in metabolic disorders involving abnormalities of vitamin D metabolism. Other uses are in patients with hyperparathyroidism and osteoporosis. Calcium supplements frequently contain vitamin D. Other nontraditional uses of vitamin D are being investigated.

Toxicity

Excessive consumption of vitamin D, known as hypervitaminosis D, can cause calcium levels in the blood to reach toxic, life-threatening levels. Toxicity can also occur in the fetus.

Dietary Sources & RDA

Vitamin D has been added to milk purchased in the U.S. and it is naturally formed via the action of ultraviolet light on precursors in the skin.

Vitamin K is essential for the formation of several blood clotting factors, therefore the main symptom of a deficiency is an increased tendency to bleed. It antagonizes the action of oral anticoagulants (blood thinners) such as warfarin. Vitamin K1 (phytonadione) is found in plants, vitamin K2 (the menaquinones) is made by bacteria in the gut, and vitamin K3 (menadione) is the precursor to menaquinone-4.

Deficiency
Defective blood clotting is present in vitamin K deficiency. Symptoms can be produces by coumarin anticoagulants and by antibiotic therapy. Inadequate vitamin K may be absorbed with obstruction to bile flow since the vitamin is poorly absorbed in the absence of bile. Other forms of malabsorption from the gastrointestinal tract and certain types of liver disease may also lead to a vitamin K deficiency. Vitamin K may be given to infants with bleeding tendencies. Doses of vitamin K are individualized and should only be given with medical supervision.
 

Anatomy of the Digestive System

Digestive system is uniquely constructed to perform its specialized function of turning food into the energy you need to survive and packaging the residue for waste disposal..

Mouth

The mouth is the beginning of the digestive tract; and, in fact, digestion starts here when taking the first bite of food. Chewing breaks the food into pieces that are more easily digested, while saliva mixes with food to begin the process of breaking it down into a form your body can absorb and use.

Esophagus

Located in throat near trachea (windpipe), the esophagus receives food from mouth when swallowing. By means of a series of muscular contractions called peristalsis, the esophagus delivers food to the stomach.

 

Stomach

The stomach is a hollow organ, or "container," that holds food while it is being mixed with enzymes that continue the process of breaking down food into a usable form. Cells in the lining of the stomach secrete a strong acid and powerful enzymes that are responsible for the breakdown process. When the contents of the stomach are sufficiently processed, they are released into the small intestine.

simple stomach of Horse

 

Compound stomach of Cattle

 

Small intestine

Made up of three segments — the duodenum, jejunum, and ileum — the small intestine is a 22-foot long muscular tube that breaks down food using enzymes released by the pancreas and bile from the liver. Peristalsis also is at work in this organ, moving food through and mixing it with digestive secretions from the pancreas and liver. The duodenum is largely responsible for the continuous breaking-down process, with the jejunum and ileum mainly responsible for absorption of nutrients into the bloodstream.
Contents of the small intestine start out semi-solid, and end in a liquid form after passing through the organ. Water, bile, enzymes, and mucous contribute to the change in consistency. Once the nutrients have been absorbed and the leftover-food residue liquid has passed through the small intestine, it then moves on to the large intestine, or colon.

Pancreas

The pancreas secretes digestive enzymes into the duodenum, the first segment of the small intestine. These enzymes break down protein, fats, and carbohydrates. The pancreas also makes insulin, secreting it directly into the bloodstream. Insulin is the chief hormone for metabolizing sugar.

Liver
The liver has multiple functions, but its main function within the digestive system is to process the nutrients absorbed from the small intestine. Bile from the liver secreted into the small intestine also plays an important role in digesting fat. In addition, the liver is the body’s chemical "factory." It takes the raw materials absorbed by the intestine and makes all the various chemicals the body needs to function. The liver also detoxifies potentially harmful chemicals. It breaks down and secretes many drugs.

Gallbladder
The gallbladder stores and concentrates bile, and then releases it into the duodenum to help absorb and digest fats.

Colon  .. large intestine
The colon is a 6-foot long muscular tube that connects the small intestine to the rectum. The large intestine is made up of the cecum, the ascending (right) colon, the transverse (across) colon, the descending (left) colon, and the sigmoid colon, which connects to the rectum. The appendix is a small tube attached to the cecum. The large intestine is a highly specialized organ that is responsible for processing waste so that emptying the bowels is easy and convenient.
Stool, or waste left over from the digestive process, is passed through the colon by means of peristalsis, first in a liquid state and ultimately in a solid form. As stool passes through the colon, water is removed. Stool is stored in the sigmoid (S-shaped) colon until a "mass movement" empties it into the rectum once or twice a day. It normally takes about 36 hours for stool to get through the colon. The stool itself is mostly food debris and bacteria. These bacteria perform several useful functions, such as synthesizing various vitamins, processing waste products and food particles, and protecting against harmful bacteria. When the descending colon becomes full of stool, or feces, it empties its contents into the rectum to begin the process of elimination.

Rectum
The rectum (Latin for "straight") is an 8-inch chamber that connects the colon to the anus. It is the rectum's job to receive stool from the colon, to let the person know that there is stool to be evacuated, and to hold the stool until evacuation happens. When anything (gas or stool) comes into the rectum, sensors send a message to the brain. The brain then decides if the rectal contents can be released or not. If they can, the sphincters relax and the rectum contracts, disposing its contents. If the contents cannot be disposed, the sphincter contracts and the rectum accommodates so that the sensation temporarily goes away.

Anus
The anus is the last part of the digestive tract. It is a 2-inch long canal consisting of the pelvic floor muscles and the two anal sphincters (internal and external). The lining of the upper anus is specialized to detect rectal contents. It lets you know whether the contents are liquid, gas, or solid. The anus is surrounded by sphincter muscles that are important in allowing control of stool. The pelvic floor muscle creates an angle between the rectum and the anus that stops stool from coming out when it is not supposed to. The internal sphincter is always tight, except when stool enters the rectum. It keeps us continent when we are asleep or otherwise unaware of the presence of stool. When we get an urge to go to the bathroom, we rely on our external sphincter to hold the stool until reaching a toilet, where it then relaxes to release the contents.

Glycolysis

The Glycolytic pathway describes the oxidation of glucose to pyruvate with the generation of ATP and NADH

• It is also called as the Embden-Meyerhof Pathway

• glycolysis is a universal pathway; present in all organisms: from yeast to mammals.

• In eukaryotes, glycolysis takes place in the cytosol

• glycolysis is anaerobic; it does not require oxygen

• In the presence of O2, pyruvate is further oxidized to CO2. In the absence of O2, pyruvate can be fermented to lactate or ethanol.

• Net Reaction: Glucose + 2NAD+ + 2 Pi + 2 ADP = 2 pyruvate + 2 ATP + 2 NADH + 2 H2O

The 3 stages of Glycolysis

• Stage 1 is the investment stage. 2 mols of ATP are consumed for each mol of glucose

• Glucose is converted to fructose-1,6-bisphosphate.

• Glucose is trapped inside the cell and at the same time converted to an unstable form that can be readily cleaved into 3-carbon units.

• In stage 2 fructose-1,6-bisphosphate is cleaved into 2 3- carbon units of glycerladehyde-3-phosphate.

• Stage 3 is the harvesting stage. 4 mols of ATP and 2 mols of NADH are gained from each initial mol of glucose. This ATP is a result of substrate-level phosphorylation

• Glyceraldehyde-3-phosphate is oxidized to pyruvate

Step-wise reactions of glycolysis

• Reaction 1: Phosphorylation of glucose to glucose-6 phosphate.

• This reaction requires energy and so it is coupled to the hydrolysis of ATP to ADP and Pi.

• Enzyme: hexokinase. It has a low Km for glucose; thus, once glucose enters the cell, it gets phosphorylated.

• This step is irreversible. So the glucose gets trapped inside the cell. (Glucose transporters transport only free glucose, not phosphorylated glucose)

• Reaction 2: Isomerization of glucose-6-phosphate to fructose 6- phosphate. The aldose sugar is converted into the keto isoform.

• Enzyme: phosphoglucomutase.

• This is a reversible reaction. The fructose-6-phosphate is quickly consumed and the forward reaction is favored.

• Reaction 3: is another kinase reaction. Phosphorylation of the hydroxyl group on C1 forming fructose-1,6- bisphosphate.

• Enzyme: phosphofructokinase. This allosteric enzyme regulates the pace of glycolysis.

• Reaction is coupled to the hydrolysis of an ATP to ADP and Pi.

• This is the second irreversible reaction of the glycolytic pathway.

• Reaction 4: fructose-1,6-bisphosphate is split into 2 3-carbon molecules, one aldehyde and one ketone: dihyroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP).

• The enzyme is aldolase.

• Reaction 5: DHAP and GAP are isomers of each other and can readily inter-convert by the action of the enzyme triose-phosphate isomerase.

• GAP is a substrate for the next step in glycolysis so all of the DHAP is eventually depleted. So, 2 molecules of GAP are formed from each molecule of glucose

• Upto this step, 2 molecules of ATP were required for eachmolecule of glucose being oxidized

• The remaining steps release enough energy to shift the balance sheet to the positive side. This part of the glycolytic pathway is called as the payoff or harvest stage.

• Since there are 2 GAP molecules generated from each glucose, each of the remaining reactions occur twice for each glucose molecule being oxidized.

• Reaction 6: GAP is dehydrogenated by the enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). In the process, NAD+ is reduced to NADH + H+ from NAD.

Oxidation is coupled to the phosphorylation of the C1 carbon. The product is 1,3-bisphosphoglycerate.

• Reaction 7: BPG has a mixed anhydride, a high energy bond, at C1. This high energy bond is hydrolyzed to a carboxylic acid and the energy released is used to generate ATP from ADP. Product: 3-phosphoglycerate. Enzyme: phosphoglycerate kinase.

• Reaction 8: The phosphate shifts from C3 to C2 to form 2- phosphoglycerate. Enzyme:phosphoglycerate mutase.

• Reaction 9: Dehydration catalyzed by enolase (a lyase). A water molecule is removed to form phosphoenolpyruvate which has a double bond between C2 and C3.

• Reaction 10: Enolphosphate is a high energy bond. It is hydrolyzed to form the enolic form of pyruvate with the synthesis of ATP. The irreversible reaction is catalyzed by the enzyme pyruvate kinase. Enol pyruvate quickly changes to keto pyruvate which is far more stable.

Glycolysis: Energy balance sheet

• Hexokinase: - 1 ATP

• Phosphofructokinase: -1 ATP

• GAPDH: +2 NADH

• Phsophoglycerate kinase: +2 ATP

• Pyruvate kinase: +2 ATP

Total/ molecule of glucose: +2 ATP, +2 NADH

Fate of Pyruvate

• NADH is formed from NAD+ during glycolysis.

• The redox balance of the cell has to be maintained for further cycles of glycolysis to continue.

• NAD+ can be regenerated by one of the following reactions /pathways:

• Pyruvate is converted to lactate

• Pyruvate is converted to ethanol

• In the presence of O2, NAD+ is regenerated by ETC. Pyruvate is converted to acetyl CoA which enters TCA cycle and gets completely oxidized to CO2.

Lactate Fermentation

• Formation of lactate catalyzed by lactate dehydrogenase:

CH3-CO-COOH + NADH + H+

CH3-CHOH-COOH + NAD+

• In highly active muscle, there is anaerobic glycolysis because the supply of O2 cannot keep up with the demand for ATP.

• Lactate builds up causing a drop in pH which inactivates glycolytic enzymes. End result is energy deprivation and cell death; the symptoms being pain and fatigue of the muscle.

• Lactate is transported to the liver where it can be reconverted to pyruvate by the LDH reverse reaction

Ethanol fermentation

• Formation of ethanol catalyzed by 2 enzymes

• Pyruvate decarboxylase catalyzes the first irreversible reaction to form acetaldehyde: CH3-CO-COOH CH3-CHO + CO2

• Acetaldehyde is reduced by alcohol dehydogenase is a reversible reaction:

CH3-CHO + NADH + H+ CH3CH2OH + NAD+

• Ethanol fermentation is used during wine-making

• Fructose is phosphorylated by fructokinase (liver) or hexokinase (adipose) on the 1 or 6 positions resp.

• Fructose-6-phosphate is an intermediate of glycolysis.

• Fructose-1-phosphate is acted upon by an aldolase-like enz that gives DHAP and glyceraldehyde.

• DHAP is a glycolysis intermediate and glyceraldehyde can be phosphorylated to glyceraldehyde-3-P.

• Glycerol is phosphorylated to G-3-P which is then converted to glyceraldehyde 3 phosphate.

• Galactose has a slightly complicated multi-step pathway for conversion to glucose-1-phosphate.

• If this pathway is disrupted because of defect in one or more enz involved in the conversion of gal to glc-1-P, then galactose accumulates in the blood and the subject suffers from galactosemia which is a genetic disorder, an inborn error of metabolism.

Entry of other sugars into glycolysis

Regulation of Glycolysis

Enzyme Activator

Hexokinase AMP/ADP

Phosphofructokinase AMP/ADP,

Fructose-2,6-bisphosphate

Pyruvte kinase AMP/ADP

Fructose-1,6-bisphosphate

Enzyme Inhibitor

Hexokinase Glucose-6-phosphate

Phosphofructokinase ATP, Citrate

Pyruvate kinase ATP, Acetyl CoA, Alanine

Regulation of Hexokinase

• Hexokinase catalyzed phosphorylation of glucose is the first irreversible step of glycolysis

• Regulated only by excess glucose-6-phosphate. If G6P accumulates in the cell, there is feedback inhibition of hexokinase till the G6P is consumed.

• Glucose-6-phosphate is required for other pathways including the pentose phosphate shunt and glycogen synthesis. So hexokinase step is not inhibited unless G-6-P accumulates. (no regulation by downstream intermediates / products of metabolism)

• Actually, liver, the site of glycogen synthesis, has a homologous enzyme called glucokinase. This has a high KM for glucose. This allows brain and muscle to utilize glucose prior to its storage as glycogen

Regulation of Phosphofructokinase

• The phosphofructokinase step is rate-limiting step of glycolysis.

• High AMP/ADP levels are activators of this enzyme, while high ATP levels are inhibitory (energy charge). In addition,

• Feed-back inhibition by Citrate, an intermediate of the TCA cycle.

• A major positive effector of phosphofructokinase is Fructose-2,6-bisphosphate. F-2,6-BP is formed by the hormone-stimulated phosphoylation of F-6-P. Thus, this is an example of allosteric feed-forward activation

Formation of Fructose-2,6-bisphosphate

• Concentration of F-2,6-BP is regulated by the action of phosphofructokinase 2 (PFK2) and fructose bisphosphatase 2 (FBPase2).

• Both enzymes are distinct domains of the same polypeptide

• When glucose levels are low, glucagon levels are high (insulin and glucagon have opposing functions). PKA is activated, which in turn inactivates PFK2 by phosphorylation. At the same time FBPase2 is activated. F-2,6-BP is converted to F-6-P which enters gluconeogensis for synthesis of glucose. In the absence of F-2,6-BP, PFK is not activated and glycolysis pauses

• When glucose levels are high, glucagon levels are low. PKA is inactive but a phosphatase dephosphorylates PFK2 and activates it. PFK2 converts F-6-P to F-2,6-BP which is a allosteric activator of PFK, the glycolytic enzyme.

Regulation of pyruvate kinase

• If glycolysis gets past the phosphofructokinase step, then regulation is at the pyruvate kinase step.

• Pyruvate kinase activity is inhibited under low glucose conditions by covalent phosphorylation

• If fructose 1,6 bisphosphate is formed, it acts a allosteric feedforward activator and drives the pyruvate kinase reaction forward.

• Other positive effectors are AMP and ADP while ATP is a negative effector.

• Alanine, an aminoacid derived from pyruvate, is a negative effector of catabolism. Alanine levels signal the anabolic state of a cell. High alanine levels indicate that the cell has enough starting material for anabolic reactions and so catabolism (which provides the ingredients for anabolism) can be paused.

Gluconeogenesis

• Gluconeogenesis is the synthesis of glucose from noncarbohydrate precursors including pyruvate, lactate, glycerol and aminoacids

• In animals the gluconeogenesis pathway is, for the most part, the reverse of glycolysis. There are substitute or bypass reactions for the irreversible steps of glycolysis.

• Glycerol enters reverse glycolysis as DHAP by the action of glycerol kinase followed by dehydrogenase

• Lacate is converted to pyruvate by LDH. Aminoacids are converted to either pyruvate or oxaloacetate prior to gluconeogenesis.

Bypass for Puruvate Kinase

• Three steps of glycolysis are irreversible and therefore need bypass reactions for gluconeogenesis.

• Pyruvate to PEP: Pyruvate synthesized by glycolysis or from aa is in the mitochondria. Here, pyruvate is first converted to oxaloacetate by the enzyme pyruvate carboxylase. One carbon is supplied by CO2 to form the 4-C oxaloacetate. The reaction is coupled to ATP hydrolysis making this a ligation reaction.

• Oxaloacetate is shuttled out to the cytoplasm where the glycolytic enzymes are located. Oxaloacetate is converted to PEP by the enzyme PEP carboxykinase. CO2 is removed and energy in the form of GTP is utilized.

• Two high energy molecules with a total free energy change of 62 kJ/mol are used up for the formation of PEP. This is consistent with the free energy change for hydrolysis of the enoyl phosphate bond.

Bypass for PFK and Hexokinase.

• PEP can be converted to fructose-1,6 bisphosphate by reverse glycolysis.

• F-1-6 BP to F-6-P cannot proceed by reverse glycolysis since the PFK reaction is irreversible.

• Instead a different enzyme called as fructose-1,6 bisphosphatase is used. This removes the P from the 1 position. However, no ATP is formed.

• Further reverse glycolysis leads to formation of glucose-6-P

• This is converted to Glc by the action of glc-6-phosphatase since the hexokinase reaction is irreversible.

• Net Reaction for gluconeogenesis:

• 2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H+ + 6 H2O glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi.

• (Net reaction for glycolysis is: Glucose + 2NAD+ + 2 ADP + 2 Pi 2 pyruvate + 2 ATP + 2 NADH + 2 H2O)

Regulation of Gluconeogenesis

• Fructose 1-6-bisphosphatase is co-ordinately regulated with phosphofructokinase. Thus, citrate is a positive effector and AMP and F-2,6-BP are negative effectors.

• When glucose levels are high, F-2,6-BP is high and gluconeogenesis is inhibited while glycolysis is favored. When glucose levels are low, F-2,6-BP is low and glycolysis is inhibited.

• Pyruvate carboxylase is an imp regulatory step in gluconeogenesis. Acetyl CoA and ATP are positive effectors while AMP/ADP are inhibitors

• glycolysis and gluconeogenesis are regulated by hormones. Insulin stimulates synthesis and activity of glycolytic enzymes while glucagon turns on gluconeogenic enzymes.

Substrate cycle or Futile cycle

• A pair of non-reversible reactions that cycle between two substrates are called as a substrate cycle

• In such a cycle, there is expense of ATP without a coupled biosynthetic reaction, thus, it is also called as a futile cycle

• Eg: F-6-P + ATP (PFK)F-1,6-BP + ADP F-1,6-BP + H2O FBPaseF-6-P + Pi

• Net: ATP + H2O ADP + Pi + energy (heat)

• Level of substrate cycling is very minimal because of reciprocal regulation of the enzymes

• Certain organisms utilize such reactions to maintain body temperature

Cori Cycle

• Lactate is formed in the active muscle to regenerate NAD+ from NADH so that glycolysis can continue.

• The muscle cannot spare NAD+ for re-conversion of lactate back to pyruvate.

• Thus, lactate is transported to the liver, where, in the presence of oxygen, it undergoes gluconeogenesis to form glucose.

• The glucose is supplied by the liver to various tissues including muscle.

• This inter-organ cooperation during high muscular activity is called as the Cori cycle.