Water-soluble Vitamins A) B-Complex 1.Thiamine (B 1 ) Sources:
whole-grain cereals, meats, legumes, nuts Active form is thiamine
pyrophosphate (TPP) Functions : 1.Oxidative decarboxylation of
pyruvic acids,conversion of pyruvic acid to acetyl coA. 2.In
transketolation reaction,transfer of ketol group. 3.TPP is also
essential for the process of nerve conduction and structure of
nerve membrane. Deficiency: Deficiency: most common in alcoholics
and malnourished individuals Decreased ATP production
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Wet beri-beri :Affects cardiovascular system 1. Extensive
edema. 2. Congestive heart failure. Dry beri-beri : Affects nervous
system. 1. Polyneuritis. 2. Hyperesthesia Muscle wasting and loss
of weight. Wernickes disease 1. Occular distrubance 2.Ataxia
2. Riboflavin (B 2 ) (UV sensitive) Sources: milk, eggs, meat,
poultry, fish, green leafy vegetables Active forms are FMN and FAD
FAD: cofactor in succinate dehydrogenase reaction (TCA) FMN:
component of ETC accepts 2 electrons from NADH in NADH
dehydrogenase reaction Deficiency: Deficiency: not associated with
major human disease but commonly seen in conjunction with other
vitamin deficiencies Deficiency symptoms include: dermatitis
cheilosis glossitis
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Occular disturbance. 1. photophobia 2. vascularization of
cornea. Angular stomatitis: inflammation of angles of mouth. 3.
Seborrheic dermatitis:inflammtion of sebaceous glands of skin.
Requirements: 1.3 -1.7 mg/day.
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3. Niacin (nicotinic acid) (B 3 ) Sources: meat, whole-grain
cereals, synthesis from tryptophan-containing foods (milk, eggs)
Active forms are NAD + and NADP + Excess tryptophan is metabolized
to niacin and supplies approx. 10% of RDA Clinical correlations:
deficiency causes pellagra(4D) RDA effective in treatment of type
IIb hyperlipoproteinemia ( reduces lipolysis of fatty acids,
activates lipoprotein lipase, less VLDL and LDL)
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Niacin 13-19mg/day depending upon the age and sex Tryptophan 13
x 60 mg/day to 19 x 60 mg/day. Hypervitaminonsis 1. Skin flushing.
2. Gastrointestinal disturbance. 3. Pruritis
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4. Pantothenic acid (B 5 ) present in a wide variety of foods
esp. eggs, liver, yeast Active form is Cofactor A (i.e. succinyl
CoA, acetyl CoA, fatty acyl CoA) part of fatty acid synthase
complex Clinical correlations: deficiency is uncommon no RDA
established
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5. Pyridoxine, pyridoxal, pyridoxamine (B 6 derivatives)
Sources: whole-grain cereals, eggs, meat, fish, soybeans, nuts
Active form is pyridoxal phosphate Important function in
transamination, deamination, decarboxylation, and condensation
reactions
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Clinical correlations: Isoniazid (isonicotinic acid hydrazide)
used to treat TB may induce B6 deficiency -> need B6 supplement
while taking isoniazid Deficiencies seen in alcoholics, infants
given deficient formula, and women on oral contraceptives Toxicity:
neurological symptoms if >2g/day
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6. Cobalamin (B 12 ) contains Co, corrin ring system Sources:
meats, shellfish, poultry, eggs, dairy products (not present in
plants) Active forms are 5-deoxyadenosylcobalamin (fatty acid
oxidation) and methyl cobalamin (met synthesis) Needed for
synthesis of methionine from homocysteine, forming tetrahydrofolate
isomerization of methyl malonyl CoA to succinyl CoA. Vit B12 hepls
in the formation of myelin sheath through the metabolism of odd
numbers fatty acids.
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Vitamin B 12 Metabolism 1.The absorption of vitamin B12,it
combines with a glycoprotein secreted by the gastric parietal cells
called intrinsic factors 2.This IF-B12 complex binds with specific
ileal receptors. 3.A pH above 6 and Ca ions required to promote
vitamin absorption. 4.Vitamin B12 passes via portal circulation to
the liver to the general circulation. 5.Vitamin B12 is carried in
the plasma by number of carrier globulins,namely transcobalmin
II,transcobalmin I and R proteins.They transport B12 to the
tissue.It bind to specific cell receptor cell surface to enter the
cell.
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Clinical correlations: Deficiency causes accumulation of
abnormal fatty acids -> neurological effects Pernicious anemia
not usually a vitamin deficiency but inability to absorb B12 (no
intrinsic factor) because of autoimmune destruction of parietal
cells Treatment: Lifetime intramuscular injections of
cyanocobalamin Anemia reversible, but not CNS effects
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deficiency in either vitamin B12 or folic acid causes increase
in plasma homocysteine levels, which damages blood vessels and
poses a risk for thrombosis megaloblastic anemia must be treated
with both folate and vitamin B12 other causes of B12 deficiency:
pure vegan diet terminal ileal disease (i.e. Chrons disease)
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6. Biotin Sources: bacterial synthesis in intestine,egg
yolk,yeast, animal tissues and tomatoes. Important function as
cofactor in carboxylation reactions (I.e. pyruvate carboxylase,
acetyl CoA carboxylase) Clinical correlations: Deficiency
(uncommon) caused by: 1. eating raw egg whites (contain avidin) 2.
broad-spectrum antibiotics (kill intestinal bacteria)
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7. Folic acid Sources: green leafy vegetables, liver, lima
beans, whole- grain cereals Active forms are tetrahydrofolate
derivatives Important in 1-C transfer reactions especially in DNA
synthesis Metabolism: 1.Folic acid ingested as polyglutamates ->
converted to monoglutamates in jejunum by intestinal conjugase
enzyme 2.Monoglutamate is reabsorned in jejunum. 3.Folic acid
circulated and is measured in blood as methyltetrahydrofolate.
4.Only a 3-4 month supply is stored in the liver.
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Clinical correlations: Folic acid deficiency is most common
vitamin deficiency in U.S., most common in pregnant women and
alcoholics Folic acid before pregnancy reduces risk of neural tube
defects.
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Deficiency caused by: 1. Diet lacking in fruit and vegetable 2.
Drugs: methotrexate, trimethoprim (chemotherapeutic drugs which
inhibit dihydrofolate reductase thus preventing purine and
pyrimidine biosynthesis -> kills blast cells and causes
macrocytic anemia) 4. Oral contraceptives (block reabsorption of
monoglutamate in jejunum) 5. Alcohol (block reabsorption of
monoglutamate in jejunum) 6. Rapidly-growing cancers (malignant
cells use folic acid) 7. Small bowel malabsorption (I.e. celiac
disease) 8. Sulfa drugs (sulfanilamide) inhibits folic acid
synthesis
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B. Non-B-Complex B. Non-B-Complex Ascorbic acid Source: citrus
fruits, potatoes, tomatoes, green vegetables Action coenzyme in
hydroxylation reactions esp. proline and lysine in collagen
synthesis antioxidant activity helps prevent formation of free
radicals Clinical correlations:Clinical correlations: deficiency
and cigarette smoking causes scurvy megadoses claimed to be
effective against common cold (very controversial) no toxic effects
but oxidized form (dehydroascorbic acid) is toxic Excess intake may
cause renal calculi (kidney stones)
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Classification and Functions of Vitamins Vitamins Fat-soluble
Vitamin A: vision, epithelial tissue, growth in children Vitamin D:
bone mineralization, blood Ca 2+ regulation Vitamin E: antioxidant
Vitamin K: clotting factor Water-soluble Energymetabolism Amino
acid metabolismRBC/NeuraldevelopmentCollagensynthesis Thiamine (B 1
) Riboflavin (B 2 ) Niacin (B 3 ) Biotin Pantothenic acid (B 5 )
Pyridoxine pyridoxal, pyridoxamine (B 6 ) Folic acid Cobalamin (B
12 ) Ascorbic acid (Vitamin C)
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Vitamin A Vitamin A consists of three biologically active
molecules, retinol, retinal (retinaldehyde) and retinoic acid
Essential for vision, reproduction, growth and maintenance of
epithelial tissues Associated with reduced heart disease, lung
cancer, skin cancer, lower cataract risk Sources: liver, kidney,
cream, butter, egg yolk RDA: 1000 retinol equivalents (RE) for
males 800 retinol equivalents (RE) for females 1 RE = 1 g retinol,
6 g -carotene, or 12 g of other carotenoids
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Each of these compounds are derived from the plant precursor
molecule, -carotene (a member of a family of molecules known as
carotenoids). Beta-carotene, which consists of two molecules of
retinal linked at their aldehyde ends, is also referred to as the
provitamin form of vitamin A. Retinol -> dietary supplements
Retinoic acid -> dermatological applications
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Metabolism of Vitamin A 1.Ingested -carotene is cleaved in the
lumen of the intestine by - carotene dioxygenase to yield retinal.
2.Retinal is reduced to retinol by retinaldehyde reductase, an
NADPH requiring enzyme within the intestines.
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vision is the function of 11-cis retinal coupled to opsin to
form rhodopsin Rhodopsin is coupled to a G-protein called
transducin. When exposed to light 11-cis is converted to
all-trans-retinal. This conformational change activates transducin.
Increased GTP binding. cGMP maintains Na + channels in open state
activation of cGMP phosphodiesterase drop in cGMP closes channels
and leads to hyperpolarization of the rod cell Vision and the Role
of Vitamin A
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Additional Roles of Retinol 1.Growth retinoic acid required for
appetite, bone growth 2.Spermatogenesis (males) and prevention of
fetal resorption (females) requires retinal or retinol (retinoic
acid doesnt work!) 3.Maintenance of epithelial cells + mucus
secretion
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Vitamin A - Clinical Correlations 2. Acne, psoriasis Retinoic
acid used to treat mild acne (Dariers disease) Tretinoin (all-trans
retinoic acid) used to treat skin aging (topical) Isotretinoin
(13-cis retinoic acid) used to treat severe acne (oral admin) **
teratogenic contraindicated for women with childbearing potential
prolonged treatment with isotretinoin causes hyperlipidemia and
increased LDL/HDL ratio
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Vitamin A - Clinical Correlations 1.Dietary Deficiency treated
with retinol or retinyl esters night blindness early sign of
Vitamin A deficiency increased susceptibility to infection and
cancer severe deficiency leads to progressive keratinization of the
cornea (xerophthalmia)
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Vitamin A - Clinical Correlations 3. Toxicity Hypervitaminosis
A = > 7.5 mg per day Early signs of Hypervitaminosis A : dry,
pruritic skin, hepatomegaly, rise in intracranial pressure (can
mimic brain tumor) teratogenic
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Sources : generated from the provitamin ergosterol(in
plants)and 7- dehydrocholesterol(in human and animals) by ultra
violet irradiation of sun. Liver,egg and yeast are rich diet Fish
liver oils.cod liver oil,shark liver oil.
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Metabolism of Vitamin D D 2 and D 3 are activated in vivo by 2
sequential hydroxylation reactions 1. 25-hydroxylase in liver
2.25-cholecalciferol-1-hydroxylase in kidney product is
1,25-dihydroxycholecalciferol (1,25-diOH D 3 )
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Function of Vitamin D to increase plasma Ca 2+ stimulates
calcium (and phosphate) uptake by intestine by inducing synthesis
of a calcium-binding protein increases calcium reabsorption by the
kidney mobilizes bone calcium by resorption
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Vitamin D - Clinical Correlations Deficiency of vitamin D
1.Rickets in children collagen matrix formed but mineralization is
incomplete soft pliable bones bow-legged mutation in vitamin D
receptor can cause vitamin D- independent rickets 2. Osteomalacia
in adults demineralization of bones = fractures (less sunlight)
problem more severe 3. Renal rickets (renal osteodystrophy) =
chronic renal failure results in low synthesis of 1,25 vitamin D 3
(calcitrol) calcitrol supplementation is effective treatment
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Toxicity Very toxic vitamin D can be stored -> accumulates
in liver and fat high doses = loss of appetite, nausea, thirst,
hypercalcemia (leads to calcium deposits in arteries and kidneys
Vitamin D - Clinical Correlations
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Three forms : K1,K2 and K3 Sources: 1. leafy vegetable(K1),
intestinal flora present in small intestine (K2),K3 is synthetic,it
is water soluble and more potent than vitamin K1 and K2.
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Vitamin K Role = posttranslational carboxylation of blood
clotting factors Sources: cabbage, cauliflower, spinach, egg yolk,
liver, synthesis from intestinal bacteria RDA: no RDA but
recommendation is 70-140 g/day Exists in several forms:
phylloquinone = vitamin K 1 (plants) menaquinone = vitamin K 2
(intestinal bacteria) menadione = synthetic derivative of vitamin K
1
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Interaction of prothrombin with platelets -carboxylates chelate
calcium and allow prothrombin to associate with membrane
phospholipids in platelets 2. conversion to thrombin is
stimulated
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Vitamin K - Clinical Correlations Deficiency of vitamin K
deficiencies are unusual antibiotic treatment can lead to
hypothrombinemia in undernourished/ very ill patients second
generation cephalosporins have warfarin-like activity supplement
treatment with vitamin K newborns are deficient and breast milk
below RDA prophylactic i.m. injection can be used
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Toxicity prolonged treatment causes hemolytic anemia, jaundice
in infants (rbc membrane effects) Vitamin K - Clinical
Correlations
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Vitamin E 8 different types -tocopherol is most common absorbed
in intestines Major storage site is adipose tissue function
antioxidant activity inhibits nonenzymatic oxidation by free
radicals sources vegetable oils, liver, eggs RDA = 10 mg/day for
males 8 mg/day for females RDA increases as intake of
polyunsaturated fats increases
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Vitamin E - Clinical Correlations Deficiency restricted to
premature infants in adults, deficiency associated with defective
lipid transport/absorption -> results rbc membrane fragility,
abnormal cell membranes Toxicity none known
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Vitamin E - Clinical Correlations Benefits may protect against
chronic disease (heart disease, cancer, cataracts, aging) due to
its antioxidant activity
