Vitamins

1. • Vitamins

2. Acknowledgment
• Addisa Ababa University
• Haramaya University
• Hawassa University
• Jimma University
• University of Gondar
• American Society for Clinical Pathology
• Center for Disease Control and
Prevention-Ethiopia

3. Chapter objective
• At the end of this chapter the students
should be able to
• Discuss the basic classification of vitamins
• Explain Sources, physiological functions and
deficiency of vitamins
• Explain the differences between water soluble
and fat soluble vitamins
• Explain diseases associated with deficiency of
vitamins

4. Outline
• 5.0. Definition of vitamins
• 5.1. Biochemistry and classification
• 5.2. Water soluble vitamins
• 5.2.1. B1 Thiamin
• 5.2.2. B2 Riboflavin
• 5.2.3. Niacin Nicotinic acid, nicotinamide

5. Outline cont’d
• 5.2.4. B6 Pyridoxine, pyridoxal, pyridoxamine
• 5.2.5. Folic acid
• 5.2.6. B12 Cobalamin
• 5.2.7. Pantothenic acid
• 5.2.8. H Biotin
• 5.2.9. C Ascorbic acid

6. Outline cont’d
• 5.3. lipid soluble vitamins
• 5.3.1. A Retinol, β-carotene
• 5.3.2. D Calciferol
• 5.3.3. E Tocopherols, tocotrienols
• 5.3.4. K Phylloquinone, menaquinones

7. • 5.0. Vitamins
• Vitamins are a group of organic nutrients
required in small quantities for a variety of
biochemical functions.
• Generally, cannot be synthesized by the body
and must therefore be supplied in the diet.

8. • 5.1. Classification
• The water-soluble vitamins comprise the B
complex and vitamin C and function as enzyme
cofactors.
• The lipid-soluble vitamins are non polar
hydrophobic compounds that can only be
absorbed efficiently when there is normal fat
absorption.
• They are transported in the blood, like any other
non polar lipid, in lipoproteins or attached to
specific binding proteins.

9. • Conditions affecting the digestion and absorption
of the lipid-soluble vitamins such as steatorrhea
and disorders of the biliary system can all lead to
deficiency syndromes.
• In contrast to water-soluble vitamins, which must
be a part of our daily diet, fat-soluble vitamins
can be stored in the body in amounts sufficient
for many months.

10. • 5.2. Water soluble vitamins
• 5.2.1. B1 Thiamin
• Thiamin has a central role in energy-yielding
metabolism, and especially the metabolism of
carbohydrate.
• Thiamin diphosphate is the coenzyme for three
multi-enzyme complexes that catalyze oxidative
decarboxylation reactions: these are

11. • Pyruvate dehydrogenase in carbohydrate
metabolism
• α-ketoglutarate dehydrogenase in the citric acid
cycle
• Branched-chain keto-acid dehydrogenase involved
in the metabolism of leucine, isoleucine, and valine.

12. • It is also the coenzyme for transketolase, in the
pentose phosphate pathway.
• In each case, the thiamin diphosphate provides
a reactive carbon

14. • Thiamin deficiency can result in the following
distinct syndromes:
• A chronic peripheral neuritis, beriberi, which may
or may not be associated with heart failure and
edema
• Wernicke’s encephalopathy with Korsakoff’s
psychosis, which is associated especially with
alcohol and drug abuse.

15. • 5.2.2. B2 Riboflavin
• Riboflavin fulfills its role in metabolism as the
coenzymes flavin mononucleotide (FMN) and flavin
adenine dinucleotide (FAD).
• FMN is formed by ATP-dependent phosphorylation of
riboflavin, whereas FAD is synthesized by further
reaction of FMN with ATP in which its AMP moiety is
transferred to the FMN.

16. • The main dietary sources of riboflavin are milk
and dairy products. In addition, because of its
intense yellow color, riboflavin is widely used as
a food additive.

18. • Flavin Coenzymes Are Electron Carriers in
Oxidoreduction Reactions including the
mitochondrial respiratory chain, key enzymes in
fatty acid and amino acid oxidation, and the citric
acid cycle.
• Flavin oxidases make a significant contribution to
the total oxidant stress of the body.

19. • Riboflavin deficiency is characterized by
cheilosis, lingual desquamation and a seborrheic
dermatitis.
• Riboflavin nutritional status is assessed by
measurement of the activation of erythrocyte
glutathione reductase by FAD added in vitro.

20. • 5.2.3. Niacin Nicotinic acid, nicotinamide
• Niacin was discovered as a nutrient during studies of
pellagra. It is not strictly a vitamin since it can be
synthesized in the body from the essential amino
acid tryptophan.
• 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.

21. • About 60 mg of tryptophan is equivalent to 1 mg
of dietary niacin.

23. • Pellagra is caused by deficiency of niacin and is
characterized by a photosensitive dermatitis.
• Etiology of pellagra is well established and
tryptophan or niacin will prevent or cure the
disease, additional factors, including deficiency
of riboflavin or vitamin B6, both of which are
required for synthesis of nicotinamide from
tryptophan.
• .

24. • 5.2.4. B6 Pyridoxine, pyridoxal, pyridoxamine
• Six compounds have vitamin B6 activity, these
are - pyridoxine, pyridoxal, pyridoxamine, and
their 5′-phosphates.
• The active coenzyme is pyridoxal 5′-phosphate.
• Approximately 80% of the body’s total vitamin
B6is present as pyridoxal phosphate in muscle,
mostly associated with glycogen phosphorylase.

25. • Pyridoxal phosphate is a coenzyme in amino acid
metabolism, especially in transamination and
decarboxylation.
• It is also the cofactor of glycogen phosphorylase,
where the phosphate group is catalytically
important.
• In addition, vitamin B6 is important in steroid
hormone action where it removes the hormone-
receptor complex from DNA binding, terminating
the action of the hormones.

27. • Although clinical deficiency disease is rare, there is
evidence that results in abnormalities of tryptophan
and methionine metabolism.
• Increased sensitivity to steroid hormone action may
be important in the development of hormone
dependent cancer of the breast, uterus, and
prostate, and vitamin B6 status may affect the
prognosis.

28. • 5.2.5. Folic acid
• The active form of folic acid (pteroyl glutamate)
is tetrahydrofolate.
• Tetrahydrofolate can carry one-carbon
fragments attached to N-5 (formyl, formimino, or
methyl groups),
• N-10 (formyl group), or bridging N-5 to N-10
(methylene or methenyl groups).
• 5-Formyl-tetrahydrofolate is more stable than
folate.

29. • Deficiency of folic acid itself—or deficiency of
vitamin B12, which leads to functional folic acid
deficiency—affects cells that are dividing rapidly
because they have a large requirement for
thymidine for DNA synthesis.
• Clinically, this affects the bone marrow, leading
to megaloblastic anemia.

30. • 5.2.6. B12 Cobalamin
• The term “vitamin B12” is used as a generic
descriptor for the cobalamins—those corrinoids
(cobalt containing compounds possessing the
corrin ring) having the biologic activity of the
vitamin.
• Although it is synthesized exclusively by
microorganisms, vitamin B12 is found only in
foods of animal origin, there being no plant
sources of this vitamin.

32. • Vitamin B12 is absorbed bound to intrinsic
factor, a small glycoprotein secreted by the
parietal cells of the gastric mucosa.
• Gastric acid and pepsin release the vitamin from
protein binding in food and make it available to
bind to cobalophilin, a binding protein secreted
in the saliva.
• In the duodenum, cobalophilin is hydrolyzed,
releasing the vitamin for binding to intrinsic
factor

33. • Pernicious anemia arises when vitamin B12
deficiency blocks the metabolism of folic acid,
leading to functional folate deficiency.
• This impairs erythropoiesis, causing immature
precursors of erythrocytes to be released into
the circulation (megaloblastic anemia).

34. • The commonest cause of pernicious anemia is
failure of the absorption of vitamin B12 rather
than dietary deficiency.
• This can be due to failure of intrinsic factor
secretion caused by autoimmune disease of
parietal cells or to generation of anti-intrinsic
factor antibodies.

36. • 5.2.7. Pantothenic acid
• Pantothenic acid has a central role in acyl group
metabolism when acting as the pantetheine
functional moiety of coenzyme A or acyl carrier
protein (ACP).
• The pantetheine moiety is formed after
combination of pantothenate with cysteine,
which provides the SH prosthetic group of CoA
and ACP.

37. • CoA takes part in reactions of the citric acid
cycle, fatty acid synthesis and oxidation,
acetylations, and cholesterol synthesis.
• ACP participates in fatty acid synthesis. The
vitamin is widely distributed in all foodstuffs, and
deficiency has not been unequivocally reported
in human beings except in specific depletion
studies.

39. • 5.2.8. H Biotin
• Biotin is widely distributed in many foods as
biocytin (ε-amino-biotinyl lysine), which is
released on proteolysis.
• It is synthesized by intestinal flora in excess of
requirements.

40. • Deficiency is unknown except among people
maintained for many months on parenteral
nutrition and,
• A very small number who eat abnormally large
amounts of uncooked egg white, which contains
avidin, a protein that binds biotin and renders it
unavailable for absorption.

41. • Biotin functions to transfer carbon dioxide in a
small number of carboxylation reactions.
• A holocarboxylase synthetase acts on a lysine
residue of the apoenzymes of acetyl-CoA
carboxylase, pyruvate carboxylase, propionyl-
CoA carboxylase, or methylcrotonyl-CoA
carboxylase to react with free biotin to form the
biocytin residue of the holoenzyme.

42. • The reactive intermediate is Ncarboxybiocytin,
formed from bicarbonate in an ATPdependent
reaction.
• The carboxyl group is then transferred to the
substrate for carboxylation

44. • 5.2.9. Vitamin C
• Is a vitamin for human beings and other
primates, the guinea pig, bats, birds, and most
fishes and invertebrates 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 that pathway due to absence of
gulonolactone oxidase.

45. • Both ascorbic acid and dehydroascorbic acid
have vitamin activity.

46. • Ascorbic acid has specific roles in the copper-
containing hydroxylases and the α-ketoglutarate-
linked iron-containing hydroxylases.
• It has a number of nonenzymic effects due to its
action as a reducing agent and oxygen radical
quencher.

48. • 5.3. lipid soluble vitamins
• 5.3.1. A Retinol, β-carotene
• Comprise retinol, retinaldehyde, and retinoic
acid (preformed vitamin A, found only in foods of
animal origin); carotenoids, found in plants,
• Comprise carotenes and related compounds,
known as provitamin A, as they can be cleaved
to yield retinaldehyde and hence retinol and
retinoic acid.

50. • Functions
• Involve in vision
• A most important function of vitamin A is in the
control of cell differentiation and turnover.
• All-transretinoic acid and 9-cis-retinoic acid
regulate growth, development, and tissue
differentiation;

51. • 5.3.2. vitamin D (Calciferol)
• 7-Dehydrocholesterol undergoes a non enzymic
reaction on exposure to ultraviolet light, yielding
previtamin D.
• This undergoes a further reaction over a period
of hours to form the vitamin itself, cholecalciferol,
which is absorbed into the bloodstream.

52. • In the liver, cholecalciferol, which has been
synthesized in the skin or derived from food, is
hydroxylated to form the 25-hydroxy derivative
calcidiol.
• This is released into the circulation bound to a
vitamin D-binding globulin which is the main
storage form of the vitamin.

53. • In the kidney, calcidiol undergoes either 1-
hydroxylation to yield the active metabolite 1,25-
dihydroxyvitamin D (calcitriol) or 24-hydroxylation
to yield an inactive metabolite, 24,25-
dihydroxyvitamin D (24 hydroxycalcidiol).
• Ergocalciferol from fortified foods undergoes
similar hydroxylations to yield ercalcitriol.

55. • 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
demineralization of bone in women who have
little exposure to sunlight, often after several
pregnancies.

56. • 5.3.3. Vitamin E, Tocopherols, tocotrienols
• E is the generic descriptor for two families
of compounds, the tocopherols and the
tocotrienols (compounds having similar
vitamin activity) have different biologic
potencies;
• The most active is D-α-tocopherol

57. • The main function of vitamin E is as a chain-
breaking, free radical trapping antioxidant in cell
membranes and plasma lipoproteins.
• It reacts with the lipid peroxide radicals formed
by peroxidation of polyunsaturated fatty acids
before they can establish a chain reaction.
• Free radical then undergoes enzymatic or
nonenzymic reaction to yield ascorbate and
dehydroascorbate, neither of which is a free
radical.

58. • 5.3.4 vitamin k, Phylloquinone, menaquinones
• Vitamin K was discovered as a result of
investigations into the cause of a bleeding
disorder hemorrhagic (sweet clover) disease of
cattle, and of chickens fed on a fat-free diet.
• Vitamin K are used to reduce blood coagulation
in patients at risk of thrombosis—the most widely
used agent is warfarin.

59. • Three compounds have the biologic activity of
vitamin K phylloquinone, the normal dietary
source, found in green vegetables;
menaquinones, synthesized by intestinal
bacteria, with differing lengths of side-chain;
menadione, menadiol, and menadiol diacetate,
synthetic compounds that can be metabolized to
phylloquinone.

60. • Vitamin K is the cofactor for the carboxylation of
glutamate residues in the post-synthetic
modification of proteins to form the unusual
amino acid γ-carboxyglutamate (Gla), which
chelates the calcium ion.
• Initially,vitamin K hydroquinone is oxidized to the
epoxide which activates a glutamate residue in
the protein substrate to a carbanion, that reacts
nonenzymically with carbon dioxide to form γ-
carboxyglutamate.

62. Review questions
• List vitamins which are lipid soluble and water
soluble.

63. • Summary
• Vitamins are organic nutrients with essential
metabolic functions, generally required in small
amounts in the diet because they cannot be
synthesized by thebody.
• The lipid-soluble vitamins (A, D, E, and K) are
hydrophobic molecules requiring normal fat
absorption for their efficient absorption and the
avoidance of deficiency symptoms.
• Next chapter will be oxidative phosphorylation

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