VITAMINS STRUCTURE AND FUNCTION

n VITAMINS STRUCTURE AND FUNCTION

n  Vitamins are organic molecules, required in small quantities for a variety of biochemical functions.

n  Act as cofactors for enzymatic reactions.

n  Cannot be synthesized by mammalian cells and, therefore, must be supplied in the diet.

q The water-soluble vitamins are composed of the B vitamins and vitamin C; they function mainly as enzyme cofactors.

q Deficiency of a single vitamin of the B complex is rare, since poor diets are most often associated with multiple deficiency states.

n  For any nutrient, there is a range of intakes between that which is clearly inadequate, leading to clinical deficiency disease, and that which is excess of the body's metabolic capacity, leading to toxicity.

n Thiamin  B₁

n  It is derived from a substituted pyrimidine and a thiazole which are coupled by a methylene bridge.

n  Rapidly converted to its active form, thiamin pyrophosphate (TPP), in the brain and liver by specific enzymes, thiamin diphosphotransferase.

n  The Recommended Dietary Allowance (RDA) is 1.0 - 1.5 mg/day for normal adults.

n  If the carbohydrate content of the diet is excessive, thiamin intake will be required.

n  It is present in all plant and animal tissues but the content is usually small (unrefined cereal grains & meat are good sources).

q The severe thiamin deficiency disease known as Beriberi is the result of a diet that is carbohydrate rich and thiamin deficient.

q An additional disease is known as Wernicke-Korsakoffsyndrome. This disease is most commonly found in chronic alcoholics.

n Riboflavin B₂

q Heterocyclic ring isoalloxazine ring attached to sugar alcohol ribitol.

n  Colored, heat stable, fluorescent, but decomposes in the visible light.

n  The normal daily requirement  is 1.2 - 1.7 mg/day for normal adults

n  Eggs, milk, meat liver & kidney and cereals.

¨ Riboflavin is the precursor for the coenzymes, flaking mononucleotide (FMN & (flavin adenine dinucleotide (FAD).

¨ FMN & FAD serves as prosthetic groups for oxidoreductase enzymes

¨ FMN is formed by phosphorylation of  riboflavin and FAD by further reaction with ATP

¨ Clinical Significances of Riboflavin Deficiency

¨ Is rare & is often seen in chronic alcoholics due to their poor food habits.

¨ Symptoms  include, glossitis, seborrhea, angular stomatitis, cheilosis and photophobia.

¨ Also occur in newborns treated for hyperbilirubinemia by phototherapy.

¨ Drugs e.g. choropromazine, thyroid hormone & ACTH affect the conversion of riboflavin to its cofactor form.

n Niacin B₃

n  A monocarboxylic acid derivative of pyridine

n  Nicotinate is required for the synthesis of the active forms of vitamin B₃, (NAD⁺) and (NADP⁺).

n  Tryptophan can be converted to NAD, requires vitamins B₁, B₂ and B₆.

n  Both NAD⁺ and NADP⁺ function as cofactors for numerous dehydrogenase, e.g., lactate and malate dehydrogenases.

¨ The ability to utilize tryptophan for niacin synthesis is inefficient (60 mg of tryptophan are required to synthesize 1 mg of niacin).

¨ RDA for niacin is 13 - 19 niacin equivalents (NE) per day for a normal adult. One NE is equivalent to 1 mg of free niacin).

¨ A diet deficient in niacin (as well as tryptophan)

¨ leads to glossitis of the tongue, dermatitis, weight loss, diarrhea, depression and dementia. this condition is known as pellagra.

1.         Hartnup disease

2.      Malignant carcinoid syndrome

3.      Drug therapies (e.g. isoniazid)

Can lead to niacin deficiency.

n  Nicotinic acid (but not nicotinamide) when administered in pharmacological doses of 2 - 4 g/day has been shown to be a useful therapeutic for hypercholesterolemia.

n  The action of nicotinic acid is a reduction in fatty acid mobilization from adipose tissue.

n  High intake will cause liver damage.

n Pantothenic Acid  B5

q Is formed by combination of  B- alanine and pantoic acid.

q Deficiency of pantothenic acid is extremely rare due to its widespread distribution  in food, whole grain cereals & meat.

Symptoms of pantothenate deficiency are difficult to assess

q The burning foot syndrome in prisoners of war has been associated with reduced capacity for acetylation.

n Vitamin B₆

n  Consist of 3 closely related pyridine derivatives.

n  All three compounds are  converted to the biologically active form of the vitamin,  pyridoxal phosphate.

n  This  is catalyzed by the ATP requiring enzyme,  pyridoxal kinase.

n  RDA is 1.4 - 2.0 mg/day for a normal adult.

n  Liver ,meat, banana, eggs are good sources

n Biotin

q Imidazole derivative ,widely distibuted in natural food.

n  Synthesised from intestinal bacteria so deficiency occur as a result of a defect in utilization.

n  Deficiencies are rare

n  Depression, muscle weakness and pain,hallucinations dermatitis.

n  Generally seen only after long antibiotic therapies which deplete the intestinal bacteria.

n  Following excessive consumption of raw eggs.

n  This is due to the affinity of the

Egg white protein, avid in

For biotin preventing intestinal

Absorption of the biotin.

n Cobalamin (B₁₂)

q Is composed of a complex tetrapyrrol ring structure (corrin ring) and a cobalt ion in the center.

n  It is synthesized exclusively by microorganisms so it is absent from plants.

n Folic Acid

q A pteridine ring structure linked to para-aminobenzoic acid (PABA)

n  It is obtained primarily from yeasts and leafy vegetables as well as animal liver.

n Ascorbic acid

n  Is derived from glucose via the uronic acid pathway.

n  The active form of vitamin C is ascorbate

n  Its main function as a reducing agent ,it  reduces cytochromes a and c, nitrate and O₂ .

n  Maintain a metal cofactor in a reduced state.

n  Hydroxylation of proline residues in collagen. Vitamin C is, therefore, required for the maintenance of normal connective tissues

n  Necessary for bone remodeling due to the presence of collagen in the organic matrix of bones.

n  The catabolism of tyrosine , oxidation of B-hydroxyphenylpyruvate to homogentisate.

n Deficiency of vitamin C

n  leads to the disease  Scurvy

n  Lipid soluble vitamins

n  Apolar hydrophobic molecules.

n  Isoprene derivatives.

n  absorbed efficiently when normal fat absorption takes place.

n  Transported in blood bound to lipoproteins or specific binding protein.

n Vitamin A

¨ consists of retinol, retinal (retinaldehyde) and retinoic acid

¨ these compounds are derived from the plant precursor molecule, b-carotene (a very effective antioxidant )

¨ Beta-carotene, consists of two molecules of retinal linked at their aldehyde ends,

¨ and is also referred to as the pro vitamin  form of vit A.

n  Retinol support the reproductive system.

n  Retinal have role in vision

n  Retinoic acid support growth and differentiation.

n Retinyl  e.ster is storage form in liver

Sources :

n  liver oils of shark

n  Milk, butter, eggs & cheese

n  Pre vitamin A : in spinach, carrots ,papaya oranges ,sweet potatoes

n  RDA 1.0 mg

¨ Clinical Significances of Vitamin A Deficiency

¨ is stored in the liver and deficiency  occurs only after prolonged lack of dietary intake.

¨ The earliest symptoms of  deficiency are night blindness.

¨ increased susceptibility to infection

¨ cancer and anemia

¨ Prolonged lack  lead to  progressive keratinization of the cornea, a condition known as xerophthalmia.

n Vitamin D

n  a steroid hormone ,

n  The biologically active is 1,25-dihydroxy vitamin D3

n  (Calcitriol )functions primarily to regulate calcium and phosphorous homeostasis.with PTH and calcitonin

n Clinical Significance of Vitamin D Deficiency

n in children is rickets and in adults is osteomalacia.

n Rickets is characterized improper mineralization during the development of the bones resulting in soft bones.

n Osteomalacia is characterized by demineralization of previously formed bone leading to increased softness and  fractures.

¨ Deficiency can occur in

n  Infants who are protected from sun light

n  Elderly, reduced ability to form vit D

n  Consuming vegetarian diet

n  Fat malabsorption syndrome

n  Kidney failure

n anti -convulsants drugs like dilantin

n Vitamin E

n  The a-tocopherol molecule is the most potent of the tocopherols.

n  It is absorbed from the intestines packaged in chylomicrons.

& delivered to the tissues via chylomicrons

n  then to the liver through chylomicron remnant uptake.

n  Destroyed by cooking and food processing

n  sunflower seed oils corn and soya bean oil are rich sources

n The major function of vitamin E is

n  to act as a natural antioxidant

n  prevents peroxidation of polyunsaturated membrane fatty acids.

n  Active a-tocopherol can be regenerated by interaction with vitamin C following scavenge of a peroxy free radical.

n  a-tocopherol can be conjugated to glucuronate for excretion in the bile.

n Clinical significances of Vitamin E Deficiency

n  in humans is an increase in red blood cell fragility. Due to short RBCs life span

n  any fat malabsorption diseases can lead to deficiencies in vit E

n Neurological disorders have been associated  with fat malabsorptive disorders.

n Vitamin K

n  When administered, vitamin K3 is alkylated to  K2 forms of menaquinone .

n  RDA is 80 mg for adult and 5-10 mg for infants .

n  Spinach , broccoli , cabbage are good sources.

n  Human milk contains tenfold lower of the vit than cow’s milk.

n  Human milk can supply only 20%

                                                    Of infat’s requirement.  

               

¨ The major function of the K

n  the maintenance of levels of the blood clotting proteins, factors II, VII, IX, X and protein C and protein S, which are synthesized in the liver as inactive precursor proteins.

n  This modification is a carboxylation requires vitamin K as a cofactor.

¨ The intestine of newborn infants is sterile, therefore, vitamin K deficiency in infants is possible if lacking from the early diet. The primary symptom of a deficiency in infants is a hemorrhagic syndrome.