Biochemistry

1. Water-Soluble
Vitamins
by :-
Zeinab Hashim
Bregdar

2.  Introduction
 Vitamins are organic molecules, required in
small quantities for a variety of biochemical
functions .
 Act as cofactors for enzymatic reactions.
 Cannot be synthesized by mammalian cells
and, therefore, must be supplied in the diet.

4.  The water-soluble vitamins are composed
of the B vitamins and vitamin C; they
function mainly as enzyme cofactors.
 Deficiency of a single vitamin of the B
complex is rare, since poor diets are most
often associated with multiple deficiency
states.

5.  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.

6.  Vitamin.
 Chemical structure.
 Sources.
 Biochemical reactions.
 Metabolism.
 Deficiency (diseases associated with Def).
 Requirements.

7. Thiamin
B1
 It is derived from a
substituted pyrimidine and
a thiazole which are
coupled by a methylene
bridge.
 Rapidly converted to its
active form, thiamin
pyrophosphate (TPP), in
the brain and liver by a
specific enzymes, thiamin
diphosphotransferase.

8.  The Recommended Dietary Allowance(RDA )
is 1.0 - 1.5 mg/day for normal adults.
 If the carbohydrate content of the diet is
excessive ,thiamin intake will be required.
 It is present in all plant and animal tissues but
the content is usually small (unrefined cereal
grains & meat are good sources).

9. Functions
TPP is necessary as a cofactor for the oxidataive
decarboxilation of α -keto acids (pyruvate , α -ketoglutarate
dehydrogenase & derivatives of branched chain amino
acids ).
 The transketolase catalyzed reactions of the pentose
phosphate pathway.
 A deficiency leads to a severely reduced capacity of cells to
generate energy as a result of its role in these reactions.

11. The earliest symptoms of thiamin deficiency ,
GIT disturbance as well as mental depression,
peripheral neuropathy and fatigue
 Chronic thiamin deficiency leads to neurological
symptoms including ataxia, mental confusion and
loss of eye coordination.
The severe thiamin deficiency disease known
as Beriber, is the result of a diet that is
carbohydrate rich and thiamin deficient.
An additional disease is known as Wernicke-
Korsakoff syndrome .This disease is most
commonly found in chronic alcoholics.

12. Measurment of thiamine deficiency:
 Erythrocytes transketolase activity .
 Excretion in urine.
 Blood thiamin concentration.

13. Riboflavin B2
 Heterocyclic ring isoalloxazine ring
attached to sugar alcohol ribitol.
 Colored ,heat stable, fluorescent,
but decomposes in the visible light.
 The normal daily requirement is
1.2 - 1.7 mg/day for normal adults
 eggs, milk, meat liver & kidney
and cereals.

14.  Riboflavin is the precursor for the coenzymes ,flavin
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
 The enzymes are termed flavoproteins or
metalloflavoproteins.
 During the course of the enzymatic reactions the reduced
forms of FMN and FAD are formed, FMNH2 and FADH2.

15. succinate dehydrogenase .
NADH dehydrogenase.
xanthine oxidase.
Acyl-coA dehydrogenase.
α -amino acid oxidase.
 mitochondrial Glycerol 3 phosphate
dehydrogenase.

16. 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. chlorpromazine, thyroid hormone &
ACTH affect the conversion of riboflavin to its
cofactor form.

17.  Assessment of Riboflavin status
 measure the urinary riboflavin .
 30 mg / day is a deficiency indication
sensitive to short term deficiency.
 Glutathione reductase extracted from
RBCs.

18. Niacin B3
 A monocarboxylic acid derivative of pyridine
 Nicotinate is required for the synthesis of
the active forms of vitamin B3, (NAD+) and
(NADP+).
 Tryptophan can be converted to NAD,
requires vitamins B1, B2 and B6.
 Both NAD+ and NADP+ function as
cofactors for numerous dehydrogenase,
e.g., lactate and malate dehydrogenases.
Nicotinamide
Nicotinic Acid

19. Conversion of nicotinate to NAD

20.  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).

21. Tryptophan metabolism

22.  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.
4. Raw fish contains enzyme( thiaminase) that
can destroy thiamin.

23.  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.
 The action of nicotinic acid is a reduction
in fatty acid mobilization from adipose
tissue.
 High intake will cause liver damage.

24. Pantothenic Acid B5
 Is fromed by combination of
B- alanine and pantoic acid.
 Deficiency of pantothenic
acid is extremely rare due to
its widespread distribution in
food, whole grain cereals &
meat.

25.  Pantothenate
 For synthesis of CoA and is a component of the acyl
carrier protein
 Absorpted readily in intestine
 By ATP form 4- phosphopantothenate.
 Addition of cystein & removal of its carboxyl group to
form 4- phosphopantitheine.
 4- phosphopantitheine is adenylylated by ATP to
form dephospho-CoA.
 Another phosphorylation to form CoA.

26.  Thiol group act as carrier of acyl radicals in CoA &
acyl carrier protein.
CoA in the metabolism:-
 Of carbohydrate via the TCA cycle
 Fatty acid synthesis and oxidation
 Acetylation reactions.
 Cholesterol synthesis .
 ACP participate in reactions concerned with fatty
acid synthesis.

27. Symptoms of pantothenate deficiency are difficult
to assess
 Since they are subtle and resemble those of other B
vitamins deficiencies.
 However, the burning foot syndrome in prisoners of
war have been associated with reduced capacity for
acetylation.

28. Vitamin B6
 Consist of 3 closely related pyridine
derivatives.
 All three compounds are converted to
the biologically active form of the
vitamin, pyridoxal phosphate.
 This is catalyzed by the ATP requiring
enzyme, pyridoxal kinase.
 All the 3 forms are absorbed from the
intestine but some hydrolysis occurs to
phosphate esters during digestion.
Pyridoxine
Pyridoxal
Pyridoxamine

29.  RDA is 1.4 - 2.0 mg/day for a normal
adult.
 Liver ,meat, banana, eggs are good
sources
 functions :-
 As a cofactor in enzymes involved in
transamination reactions ,decarbxylation,
threonine aldolase activity.
 In glycogenolysis as a cofactor for
glycogen phosphorylase.
Pyridoxal Phosphate

30. Transamination Reactions

31.  Deficiencies of vitamin B6
 Are rare and are related to an overall deficiency of all the B-
complex
 Isoniazid and penicillamine combine with B6 resulting in a
deficiency .
 During pregnancy and lactation vitamin B6 requirments
increases approximately 0.6 mg/day.
 Metabolism of ethanol to acetaldehyde which hydrolyze the
phosphate group (in alcoholics)
 Extremely high doses can cause irreversible nerve damage.

32. Biotin
 Imidazole derivative ,widely distibuted in
natural food.
 Synthesised from intestinal bacteria so
deficiency occur as a result of a defect
in utilization.
 A cofactor required of enzymes that
are involved in carboxylation reactions,
 acetyl-CoA carboxylase
 pyruvate carboxylase .

33.  Deficiencies are rare
 Depression, muscle weakness, pain, hallucinations and
dermatitis.
 Generally seen only after long antibiotic therapies which
deplete the intestinal bacteria.
 Following excessive consumption of raw eggs.
 This is due to the affinity of the
egg white protein ,avidin
for biotin preventing intestinal
absorption of the biotin .

34. Cobalamin (B12)
 Is composed of a complex tetrapyrrol ring
structure (corrin ring) and a cobalt ion in
the center.
 It is synthesized exclusively by
microorganisms so it is absent from plants.
 Is found in the liver of animals bound to
protein as methlycobalamin or 5'-
deoxyadenosylcobalamin.
 Must be hydrolyzed from protein in order
to be active.

35.  Hydrolysis occurs in the stomach by gastric acids or the
intestine by trypsin digestion following consumption of
animal meat.
 The vitamin is then bound by intrinsic factor, a protein
secreted by parietal cells of the stomach, and carried to
the ileum where it is absorbed.
 Following absorption the vitamin is transported to the
liver in the blood bound to transcobalamin II .
 Stored in the liver bound to transcobolamin 1.

36. Absorption Of The vitamin (B12)

37.  There are two clinically significant reactions in
the body that require vitamin B12 as a cofactor.
1. Methylmalonyl-Co mutase in the conversion
of methylmalonyl-CoA to succinyl-CoA.
2. The conversion of homocysteine to methionine
and is catalyzed by methionine synthase .

38. The Conversion Of Homocysteine To Methionine

39.  The liver can store up to six years worth of vitamin B12
 Pernicious anemia that develops as a result a lack of
intrinsic factor in the stomach leading to malabsorption
of the vitamin.
 It results from block in nucleotide biosynthesis. all of
the folate becomes trapped as the N5-methylTHF
derivative .
 This trapping prevents the synthesis of other THF
derivatives required for the nucleotide biosynthesis
.

40.  Neurological complications :
 Progressive demyelination of nerve cells.
 Increase in methylmalonyl-CoA, which is a
competitive inhibitor of malonyl-CoA
 Also it is able to substitute for malonyl-CoA in any fatty
acid biosynthesis
 This result in branched-chain fatty acids that alter the
normal membrane structure of nerve cells

41.  Deficiency has traditionally been based on low serum
vitamin B12 levels less than 200 pg per mL
 Measurements of metabolites such as methylmalonic acid
and homocysteine have been shown to be more sensitive
 A Schilling test, which distinguishes intrinsic factor-related
malabsorption, can be used to diagnose pernicious anemia
 Schilling test results were once used to determine whether
a patient required parenteral or oral vitamin B12.

42. Folic Acid
 A pteridine ring structure linked to para-
aminobenzoic acid (PABA)
 Folic acid is then generated through the
conjugation of glutamic acid residues to
pteroic acid
 It is obtained primarily from yeasts and
leafy vegetables as well as animal liver.
 Animal cannot synthesize PABA nor
attach glutamate residues to pteroic acid,
thus, requiring folate intake in the diet.

43.  When stored in the liver or ingested folic acid exists in a
polyglutamate form.
 Intestinal mucosal cells remove some of the glutamate residues
through the action of the lysosomal enzyme, conjugase.
 Is reduced within cells to ( H4folate) through the action of
dihydrofolate reductase (DHFR), an NADPH-requiring
enzyme.
 The function of THF derivatives is to carry and transfer
various forms of one carbon units
 The one carbon units are either methyl, methylene, methenyl,
formyl or formimino groups.

44. The Synthesis Of Tetrahydrofolate

45.  Impairment in dTMP synthesis:
 Cell cycle arrest in S-phase of rapidly proliferating cells,
in particular hematopoietic cells.
 The result is megaloblastic anemia . The inability to
synthesize DNA during erythrocyte maturation leads to
abnormally large erythrocytes .

47.  Folate deficiencies are rare due to the adequate presence
of folate in food.
 Poor dietary habits as those of chronic alcoholics can lead to
folate deficiency.
 Impaired absorption or metabolism or an increased demand
for the vitamin( pregnancy).
 Certain drugs such as anticonvulsants and oral
contraceptives can impair the absorption of folate.
 It is now agreed that a supplement of 400 µg of folic acid
taken near the time of conception will prevent most neural
tube defects (NTDs).

48. Tetrahydrofolte Synthesis Pathway

49. Ascorbic acid
 Is derived from glucose via the uronic
acid pathway.
 L-gulonolactone oxidase convert
gulonolactone to ascorbic acid is absent
in primates making ascorbic acid required
in the diet.
 The active form of vitamin C is ascorbate
 Its main function as a reducing agent ,it
reduces cytochromes a and c, nitrate and
O2 .

50.  Maintain a metal cofactor in a reduced state.
 Hydroxylation of proline residues in collagen. Vitamin C
is, therefore, required for the maintenance of normal
connective tissuse
 Necessary for bone remodeling due to the presence of
collagen in the organic matrix of bones.
 The catabolism of tyrosine , oxidation of B-
hydroxyphenylpyruvate to homogentisate.

51.  The process of steroidogenesis , the adrenal cortex
contains high levels of vitamin C which are depleted upon
(ACTH) stimulation of the gland.
 Absorption of iron is inhanced by vitamin c.
 Antioxidant in reducing oxidized tocopherol in membranes.
 Synthesis of epinephrine from tyrosine.
 Synthesis of the bile acids.

52.  Deficiency of vitamin C
 leads to the disease Scurvy.
 Easily bruised skin, muscle fatigue, soft swollen gums,
decreased wound healing and hemorrhaging, osteoporosis,
and anemia.
 It is readily absorbed and so the primary cause of deficiency is
poor diet and/or an increased requirement (stress).
 Normal levels of vitamin C lasts 3-4 month before deficiency
appears.
 Scurvy cured by consumption of fruits and fresh vegetables.

53. Deficiency Of Vitamin C Scurvy

54. References

Harper's biochemistry. 2000; 25th Robert K,
Daryl K, Victor W. Chapter 52 Structure &
Function Of Water Soluble Vitamins :P( 599
– 634).

55. Thank you