FACULTY OF MEDICINE

MEDICAL BIOCHEMISTRY

VITAMINS
ASST. PROF. DR. METE Ö Z K O Ç
 Vitamins are:
1. A group of organic nutrients,
2. required in small quantities for a variety of biochemical functions
3. cannot be synthesized by the body and must therefore be supplied in
the diet.
 The lipid-soluble vitamins are hydrophobic compounds that can be absorbed
efficiently only when there is normal fat absorption.
 They are transported by lipoproteins or specific binding proteins in blood

 The water-soluble vitamins are composed of the B vitamins and vitamin C; they
function mainly as enzyme cofactors.
 Lipid-soluble vitamins are:
 Vitamin A, D, E and K

 Water-soluble vitamins are:

 Vitamin B1 (thiamin), B2 (riboflavin), B3 (niacin), B5 (panthotenic acid), B7 (biotin),
B9 (Folik acid), B12 and C
 LIPID-SOLUBLE VITAMINS

THEY ARE SYNTHESISED FROM ISPORENE UNITS:

 VITAMIN A
 Vitamin A is found in 3 form and they are known as retinoids: and these type, ready to use, of
vitamin A molecules are only found in foods of animal origin
 Carotenoids, found in plants, are composed of carotenes and related
compounds; many are precursors of vitamin A, as they can be cleaved to
yield retinaldehyde, then retinol and retinoic acid
 Vitamin A is synthesised from provitamins (plant origin): The α-, β-, γ-
carotenes
 Although it would appear that one molecule of β-carotene should yield two of
retinol, this is not so in practice; 6 μg of β-carotene is equivalent to 1 μg of
preformed retinol
 β-Carotene and other provitamin A carotenoids are cleaved in the intestinal mucosa
by carotene dioxygenase, yielding retinaldehyde, which is reduced to retinol,
esterified and secreted in chylomicrons
IMPORTANCE OF VITAMIN A

 Vitamin A Has a Function in Vision

 The key to initiation of the visual cycle is the availability of 11-cis-retinaldehyde, and hence vitamin
A.
 Retinoic Acid Has a Role in the Regulation of Gene Expression and Tissue
Differentiation
 All-trans-retinoic acid and 9-cis-retinoic acid regulate growth, development, and tissue
differentiation; they have different actions in different tissues.
 Vitamin A deficiency is the most important preventable cause of blindness. IN its deficiency
both the time taken to adapt to darkness and the ability to see in poor light are impaired.
 Prolonged deficiency leads to xerophthalmia: keratinization of the cornea and blindness
 Vitamin A also has an important role in differentiation of immune system cells, and even mild
deficiency leads to increased susceptibility to infectious diseases
 There is only a limited capacity to metabolize vitamin A, and excessive intakes lead to
accumulation beyond the capacity of binding proteins, so that unbound vitamin A causes
tissue damage. So the excess vitamin A is toxic.
VITAMIN D

 Vitamin D is not strictly a vitamin, since it can be synthesized in the skin, and under
most conditions that is the major source of the vitamin. Only when sunlight
exposure is inadequate is a dietary source required.
 Its main function is in the regulation of calcium absorption and homeostasis; most of
its actions are mediated by way of nuclear receptors that regulate gene expression.
 It also has a role in regulating cell proliferation and differentiation.
 Skin

Liver Kidneys
 Vitamin D Deficiency Affects Children & Adults:
 In the vitamin D deficiency disease rickets, the bones of children are
undermineralized as a result of poor absorption of calcium
 Osteomalacia in adults results from the demineralization of bone, especially in
women who have little exposure to sunlight, especially after several pregnancies
 Vitamin D is toxic in excess intake
VITAMIN E

 Vitamin E does not have a precisely defined metabolic function

 It acts as:
 A lipid-soluble antioxidant in cell membranes,
 And is important in maintaining the fluidity of cell membranes.

 Vitamin E is the generic descriptor for two families of compounds, the tocopherols
and the most active is d-α-tocopherol
VITAMIN K

 VITAMIN K IS REQUIRED FOR SYNTHESIS OF BLOOD

CLOTTING PROTEINS
 Three compounds have the biological activity of vitamin K:
phylloquinone, the normal dietary source, found in
green vegetables; menaquinones, synthesized by
intestinal bacteria, with differing lengths of side-chain; and
menadiol.
 Vitamin K Is the Coenzyme for Carboxylation of Glutamate in
Postsynthetic Modification of Calcium-Binding Proteins
 In the reaction glutamate residue is converted to γ-carboxyglutamate
(recall this: is an uncommon amino acid)

 Prothrombin and several other proteins of the blood clotting

system each contain 4–6 γ-carboxyglutamate residues
 γ-Carboxyglutamate chelates calcium ions, and so permits the
binding of the blood clotting proteins to membranes
 WATER-SOLUBLE VITAMINS

WATER-SOLUBLE VITAMINS ARE IMPORTANT FOR SOME REACTIONS AS COENZYMES

VITAMIN B1 (THIAMIN)

 Thiamin has a central role in energy-yielding metabolism, and especially the

metabolism of carbohydrates
 Thiamin diphosphate (active form of vitamin) is the coenzyme for three
multi-enzyme complexes that catalyze oxidative decarboxylation reactions:
 Pyruvate dehydrogenase
 α-ketoglutarate dehydrogenase
 branched-chain keto-acid dehydrogenase
 Transketolase
 Thiamin deficiency can result in three distinct syndromes:
 A chronic peripheral neuritis, beriberi, which may or may not be
associated with heart failure and edema;
 Acute pernicious beriberi, in which heart failure and metabolic
abnormalities predominate, without peripheral neuritis;
 Wernicke encephalopathy with Korsakoff psychosis, which is
associated especially with alcohol and narcotic abuse.
 VITAMIN B2 (RIBOFLAVIN)

 Riboflavin provides the reactive moieties of the coenzymes flavin mononucleotide

(FMN) and flavin adenine dinucleotide (FAD)

Flavin Coenzymes Are

Electron Carriers
in Oxidoreduction Reactions:
These include the
mitochondrial respiratory
chain, key enzymes
in fatty acid and amino acid
oxidation, and the citric
acid cycle.
 VITAMIN B3 (NIACIN)

 Two compounds, nicotinic acid and nicotinamide, have the biologic

activity of niacin; its metabolic function is as the nicotinamide ring of the
coenzymes NAD and NADP in oxidation/reduction reactions
 Examples:
 Glucose-6-phosphate dehydrogenase (NADP+)
 Pyruvate, α-ketoglutarate and branched-chain ketoacid dehydrogenases (NAD+)
 Glyceraldehyde-3-phosphate dehydrogenase (NAD+)
 In the deficiency of niacin and tryptophan (because niacine can be synthesised from
it) pellegra is developed
 As the condition progresses, there is dementia and possibly diarrhea.
 Untreated pellagra is fatal.
 A number of genetic diseases that result in defects of tryptophan metabolism are
associated with the development of pellagra, despite an apparently adequate intake
of both tryptophan and niacin
 Hartnup disease (rare genetic condition)
 Carcinoid syndrome
 The excess niacin is toxic
VITAMIN B5 (PANTHOTENIC ACID)

 Pantothenic acid has

a central role in acyl
group metabolism
when acting as the
pantetheine
functional moiety of
coenzyme A (CoA)
or acyl carrier
protein (ACP)
VITAMIN B7 (BIOTIN)

 Biotin is widely distributed in many foods as

biocytin (ε-aminobiotinyllysine)
 uncooked egg white, which contains avidin, a
protein that binds biotin and renders it
unavailable for absorption
 Biotin functions to transfer carbon dioxide in a small number of
reactions:
 acetyl-CoA carboxylase
 pyruvate carboxylase,
 propionyl-CoA carboxylase
VITAMIN B9 (FOLIC ACID)

 The active form of folic acid is tetrahydrofolate (THF)

 The folates in foods may have up to seven additional glutamate residues.
 In addition, all of the one-carbon substituted folates may also be present in foods.
 5-formyl THF
 10-formyl THF
 5-formimino THF
 5, 10-methylene THF
 5-methyl THF
 5, 10-methenyl THF
 Tetrahydrofolate is important as one-carbon unit carrier
 Folate deficiency causes megaloblastic anemia
 Supplements of 400 μg/day of folate begun before pregnancy result in a
significant reduction in the incidence of spina bifida and other neural
tube defects.
 Elevated blood homocysteine is a significant risk factor for atherosclerosis,
thrombosis, and hypertension. The condition is the result of an impaired ability to
form methyltetrahydrofolate by methylene-tetrahydrofolate reductase, causing
functional folate deficiency, resulting in failure to remethylate homocysteine to
methionine.
VITAMIN B12

 The term “vitamin B12” is used as a generic descriptor for the

cobalamins
 Although it is synthesized exclusively by microorganisms, for practical
purposes vitamin B12 is found only in foods of animal origin, there being
no plant sources of this vitamin. This means that strict vegetarians
(vegans) are at risk of developing B12 deficiency.
• Food products of animal origin contain vitamin B12. However, the B12 is bound to proteins in these dietary
sources. To release the B12 as well as other nutrients, pepsin and acid pH in the stomach will degrade these
food proteins.
• Once the B12 is free, it binds to haptocorrin (HC), one of the three B12-binding proteins. HC is produced by
the salivary glands and the parietal cells in the stomach. In the duodenum, the pH is now less acidic, which
allows pancreatic protease to degrade the HC. Then, B12 (both newly ingested and from the bile duct) is
released again, and binds tightly to the intrinsic factor (IF) produced by parietal cells.
• In the mucosal cells of the distal ileum, the B12-IF complex is recognized by special receptors. The B12
passes through, and soon enters the blood, bound to one of two proteins. The majority (70-90%) binds to
haptocorrin again, while the rest binds to transcobalamin, forming a complex known as holotranscobalamin (or
‘active B12’). This is the biologically active fraction of vitamin B12 in the blood, as it is in only this form that
B12 can be delivered to all the cells of the body.
• Vitamin B12 absorbed in the intestine subsequently gets transported to the liver via the portal system. There
is extensive enterohepatic circulation of vitamin B12, and then B12 is transported from the liver, via the bile
duct, to the duodenum.
 There Are Three Vitamin B12–Dependent Enzymes:
 Methylmalonyl CoA mutase,
 leucine aminomutase,
 methionine synthase
 The most common cause of pernicious anemia is failure of the absorption of vitamin B12
rather than dietary deficiency. Pernicious anemia is type of megaloblastic anemia but it is
called with the special name as pernicious anemia, because it occurs with the lack of intinric
factor.
 This can be the result of failure of intrinsic factor secretion caused by autoimmune disease
affecting parietal cells or from production of anti-intrinsic factor antibodies.
 VITAMIN C (ASCORBIC ACID)

 Vitamin C is a vitamin for humans and other primates; other animals synthesize it as an intermediate in the
uronic acid pathway of glucose metabolism.
 In those species for which it is a vitamin, there is a block in the pathway as a result of absence of gulonolactone
oxidase.
 Vitamin C is the coenzyme for two groups of hydroxylases:
 Dopamine β-hydroxylase Copper containing enzymes
 peptidylglycine hydroxylase
 Proline hydroxylases
Iron containing enzymes
 Lysine hydroxylases

 Vitamin C Deficiency Causes Scurvy