The document provides an overview of water-soluble vitamins, focusing on the B complex group, highlighting their biochemical functions, clinical significance, and deficiency symptoms. Key vitamins discussed include thiamin (B1), riboflavin (B2), niacin (B3), pyridoxine (B6), biotin (B7), folic acid (B9), cyanocobalamin (B12), and pantothenic acid (B5). Each vitamin's metabolic roles, active forms, and the physiological consequences of their deficiencies are elaborated upon, emphasizing their importance in human health.

1. WATER SOLUBLE
VITAMNS

2. 1. VITAMIN B COMPLEX
Members include:
Thiamin (Vitamin B1);
Riboflavin (Vitamin B2);
Niacin;
Pyridoxine (Vitamin B6);
Biotin;
Folic acid;
Cyanocobalamin (Vitamin B12) and
Pantothenic acid.

3. THIAMIN
• A heat labile
•Highly alkaline sensitive
•Contains: Sulphur, pyrimidine and thiazole rings which are joined by
methylene bridge.

4. Biochemical function of thiamin
• Active form: Thiamin pyrophosphate (TPP)
• Formed from thiamin in presence of ATP in a reaction catalyzed by thiamin
kinase present in liver
TPP is the prosthetic group of enzymes involved in:
• Oxidative decarboxylation of ketoacids such as:
Pyruvate dehydrogenase complex (PDH) which converts
pyruvate to acetyl-CoA
α-keto glutarate dehydrogenase complex which converts α-
Ketoglutarate to succinyl-CoA.
Mitochondrial branched-chain α-ketoacid decarboxylase - catalyses
oxidative decarboxylations of branched-chain α-ketoacids formed in
the catabolism of valine, Leucine and Iso-leucine.
• Transketolase reaction of HMP shunt - Act as a carrier of ketol group.
• B1 is required in Tryptophan metabolism for the activity of Tryptophan
pyrrolase.
• Coenzyme (Co-carboxylase) of pyruvate carboxylase in yeasts for the non-
oxidative decarboxylation of pyruvate to acetaldehyde.

5. Clinical significance of Thiamine deficiency
Beriberi characterised by:
• CV manifestations include:
Palpitation, dyspnoea, cardiac hypertrophy and dilatation,
May progress to congestive cardiac failure.
• Neurological manifestations:
Predominantly those of ascending, symmetrical, peripheral
polyneuritis.
May be accompanied by an acute haemorrhagic polioencephalitis
(Wernicke’s encephalopathy).
• GI symptoms:
Anorexia is an early symptom.
May be gastric atony, with diminished gastric motility and nausea;
fever and vomiting occur in advanced stages.
Dry beriberi: Not associated with oedema.
Wet beriberi:
Associated with oedema due to
Congestive cardiac failure
Protein malnutrition (Low plasma albumin).

6. RIBOFLAVIN
•Contains heterocyclic isoalloxazine ring and ribitol a sugar alcohol

7. Biologically active forms
• Phosphorylated - riboflavin serves as the prosthetic group (as
coenzyme)
• Two main derivatives are:
FMN (Flavin mononucleotide): Phosphoric acid is attached to
ribityl alcoholic group in position 5.
Flavin-Ribityl-PO4
FAD (Flavin adenine nucleotide): Linked to an adenine
nucleotide through a pyrophosphate linkage.
Flavin-ribityl-P-P-ribose-Adenine

8. METABOLIC ROLE
Act as coenzymes in various H-transfer reactions
• Hydrogen is transported by reversible reduction of the coenzyme by two
hydrogen atoms added to the ‘N’ at positions 1 and 10, to form dihydro or
leucoriboflavin.
Principal enzyme reactions catalysed are:
• FMN
Warburg’s yellow enzyme
Cytochrome-C-reductase
L-amino acid oxidase
(Fp is autooxidisable at substrate level by molecular O2 forming H2O2)
• FAD
Xanthine oxidase (Xanthine → uric acid)
D-amino acid oxidase
Aldehyde oxidase
Fumarate dehydrogenase (Succinate → Fumarate)
Glycine oxidase
Acyl-CoA dehydrogenase
Diaphorase

9. Clinical significance of Riboflavin Deficiency diseases
In humans riboflavin deficiency causes oral, facial, occular lesions and
scrotal and vulval lesions.
Oral, facial and occular lesions are:
Angular Stomatitis. Lesions of mouth particularly at the corners of
mouth.
Cheliosis. Red swollen and cracked lips.
Dermatitis of nasolabial region.
Vascularization of cornea and conjuctiva.
Glossitis. Inflammated magenta coloured tongue.
Scrotal and vulval lesions are scrotal dermatitis and urogenital lesion

10. NIACIN (VITAMIN B3)
•Niacin refers to two pyridine derivatives:
Nicotinic acid
Nicotinamide.

11. • In tissues: Occurs as the amide (nicotinamide, niacinamide).
• The form that enters into physiological active combination

12. Biological “Active” Forms
Nicotinamide occurs as a “dinucleotide”, the pyridine ‘N’ being linked to
a D-ribose residue.
Two nucleotide active forms exist:
Nicotinamide adenine dinucleotide (NAD+)
The compound contains:
• One molecule of nicotinamide
• Two molecules of D-ribose
• Two molecules of phosphoric acid
• One molecule of adenine.

14. Metabolic Role
NAD+ and NADP+ operate as hydrogen and electron transfer agents
• In reversible oxidation and reduction.
• Hydrogen is transferred from a metabolite to NAD+
• Produce oxidized metabolite and the reduced NAD (NADH + H+)
• Reduction of NAD+ occurs in para position; one H loses an electron
and enters the medium as H+.
• Function of NADP+ is similar to that of NAD+
• The two coenzymes are interconvertible.

15. Important enzymes to which NAD+ and NADP+ act as coenzyme:
NAD+
• Alcohol dehydrogenase (Ethanol → Acetaldehyde)
• Lactate dehydrogenase (LDH) (PA ↔LA)
• Malate dehydrogenase (Malate → OAA)
• Glyceraldehyde-3-P-dehydrogenase (Gly-3-P → 1, 3-di-phosphoglycerate)
• α-Glycero-P-dehydrogenase
• Pyruvate dehydrogenase complex (PDH) (PA → Acetyl-CoA)
• α-Ketoglutarate dehydrogenase complex (α-ketoglutarate → succinyl-CoA)
NADP+
• Glucose-6-P-dehydrogenase (G-6-PD) (G-6-P → 6-Phosphogluconate)
• Glutathione reductase
Either NAD+ or NADP+
• Glutamate dehydrogenase (Glutamate → α-ketoglutarate + NH3)
• Isocitrate-dehydrogenase (Isocitrate → Oxalosuccinate)

16. Clinical significance of Niacin deficiency diseases
• Common in countries where diet of low income group consist of
maize only.
• Niacin deficiency is due to high leucine
• In man causes pellagra in which skin, gastrointestinal tract and
nervous system are affected.
• Characteristic symptoms of pellagra are:
Dermatitis: Occurs in light exposed areas of skin due to
photosensitivity. Initially exposed areas of skin develops sunburn which
then progress to pigmentation and ulceration. The most affected areas are
neck, forearms and fingers.
Diarrhoea: Occurs due to inflammation of mucous membranes of
gastrointestinal tract. If it prolongs death may occur.
Dementia: Occurs in chronic cases. Neurological disturbances like
depression, headache, delerium and memory loss are seen.

17. PYRIDOXINE (VITAMIN B6)
• Three compounds namely pyridoxine, pyridoxal and pyridoxamine
derived from pyridine show vitamin B6 activity.

18. Biological ‘active’ forms:
• Pyridoxal-PO4
• Pyridoxamine-PO4
Are the phosphorylated derivatives,
Phosphorylation involves the hydroxymethyl group –CH2OH at position
5 in the pyridine ring.
Metabolic Role
Pyridoxal P acts as a coenzyme, principally involved in metabolism of
amino acids.
Cotransaminase: Coenzyme transaminases in transamination reaction.
Codecarboxylase: Coenzyme for decarboxylases in decarboxylation
reaction. Amino acids are decarboxylated to form corresponding amines.
Examples:
Tyrosine → Tyramine + CO2
Histidine → Histamine + CO2
Glutamic acid → G A B A + CO2

19. • Deaminases (dehydrases): Catalyses non-oxidative deamination of
OH-amino acids (serine, threonine, etc).
• Kynureninase: In tryptophan metabolism, it converts 3-OH-
kynurenine to 3-OH anthranilic acid that forms nicotinic acid.
• Transulfuration: Involving transfer of –SH group, e.g.
Homocysteine + Serine → homoserine + cysteine.
• Desulfhydrases: It catalyses non-oxidative deamination of cysteine in
which H2S is liberated.
• Serine hydroxy methyl transferase: Interconversion of glycine and
serine.
• Pyridoxal-P is required as a coenzyme in the biosynthesis of
arachidonic acid from linoleic acid.
• Synthesis of Sphingomyelin: Pyridoxal-P - as a coenzyme for
activation of serine which is required for synthesis of sphingomyelin.
Required as a coenzyme for amino acid racemases:
D-Glutamic acid → L-Glutamic acid
D-Alanine → L-Alanine

20. Clinical significance of Vitamin B6 deficiency disease
Deficiency Manifestations:
• No deficiency disease but clinical manifestations occur.
• Epileptiform convulsions in infants:
Lowered activity of Glutamic acid decarboxylase.
Lower of γ-amino butyric acid (GABA) in the brain which
causes convulsions.
• Pyridoxine responsive anaemia:
A hypochromic microcytic anaemia called sideroblastic
(sideroachrestic) anaemia
High serum Fe level and haemosiderosis of Liver, spleen and
bone marrow
Pyridoxal-P is required as a coenzyme in decarboxylation of α-
amino-β-ketoadipic acid to δ-ALA in heme synthesis.
In B6-deficiency heme synthesis suffers and Fe cannot be
utilised.

21. BIOTIN (VITAMIN B7)
• Is a sulphur containing vitamin.
• Consists of imidozole ring fused to tetrahydro thiophene with valerie acid side
chain.

22. Biochemical function of biotin
Metabolic Role
• Coenzyme for carboxylases, which catalyse Carboxylation reactions.
• Biotin is first converted to carboxybiotin complex by reaction with
HCO3
– and ATP. “CO2-biotin complex’’ is the source of “active” CO2
which is transferred to the substrate.
Examples of Carboxylation
• Conversion of acetyl-CoA to Malonyl-CoA: First step of FA synthesis,
acetyl-CoA carboxylase.
• Conversion of propionyl-CoA to methylmalonyl-CoA: Propionyl-CoA
carboxylase.
• Conversion of pyruvate to oxaloacetate: Pyruvate carboxylase.
Other reactions where Biotin has been incriminated are:
• Conversion of β-methyl crotonyl-CoA to β-methyl glutaconyl-CoA: In
leucine metabolism, catalysed by β-methyl-erotonyl-CoA carboxylase.

23. • Intramitochondrial FA synthesis: Required as a coenzyme with
condensing enzyme for chain elongation of FA in intramitochondrial
FA synthesis.
• Required for “active transport” of amino acids through cell
membrane and intestinal absorption of amino acids.
• Muscle phosphorylase: As a constituent of muscle phosphorylase: 4
molecules of pyridoxal-(P) per molecule of enzyme (tetramer).
• Transport of K+: Promote transport of K+ across the membrane from
exterior to interior.
• Aminoacetone synthetase: formation of aminoacetone from acetyl-
CoA and glycine.
• Synthesis of CoA-SH (Coenzyme A):
• In porphyrin synthesis: Conversion of α-amino-β-ketoadipic acid to
δ-ALA, an important step in haem synthesis. esis suffers and leads to
anaemia.

24. Clinical significance of Biotin deficiency
No definite deficiency disease but two conditions have been found:
Congenital:
• A rare genetic deficiency of holocarboxylase synthase
• Helps to utilise biotin in metabolic role.
• Affected child cannot utilise biotin and develops biotin deficiency
• Manifested as dermatitis, graying of hair, loss of hair (alopecia) and
incoordination of movements.
• Urine has high levels of lactate, β-OH-propionate and β-methyl
crotonate due to the failure of corresponding enzyme activities.
Acquired (Leiner’s disease):
• Erythroderma desquamativum or exfoliative dermatitis in young
infants
• Occurs in breastfed infants, frequently in association with persistent
diarrhoea.
• Low biotin content of human milk together with the poor absorption
of biotin due to diarrhoea, cause biotin deficiency.

25. FOLIC ACID (VITAMIN B9)
•Consists of pteridine nucleus (pyrimidine and pyrazine rings), p-aminobenzoic
acid and glutamate.

26. • Biologically active: Reduced form Tetrahydrofolate F.H4
• Obtained by addition of four hydrogens to the pteridine at 5, 6, 7 and
8 position.
Metabolic Role
• Involved in the transfer and utilisation of the one carbon moiety
namely:
Methyl (–CH3),
Formyl (–CHO)
Formate (H.COOH)
Formimino group (–CH=NH) or
Hydroxymethyl (–CH2OH).

27. Biochemical function of folic acid
Tetrahydrofolate (FH4) is a carrier of one carbon units.
• Folic acid prevents neural tube defects (NTD) that occur during fetal
development.
• Defective folate metabolism impairs neural tube closure during
development.
• Folic acid is effective in lowering plasma homocysteine concentration
in patients with coronary artery disease.

28. Clinical significance of Folic Acid deficiency diseases
• In man megaloblastic anaemia is the main symptom.
• Most common in pregnant women and in unweaned children.
• Since folic acid is required for the synthesis of DNA through
nucleotides particularly TMP formation, rapidly dividing cells like
bone marrow or erythropoietic cells or intestinal cells are most
affected in folic acid deficiency.
• Other symptoms are:
Leucopenia and macrocytic hyperchromic anaemia.
Thrombocytopenia.
Diarrhoea and weakness.

29. CYANOCOBALAMIN (VITAMIN B12)
Structure of vitamin B12:
• Central portion (Corrin Ring system) consists of four reduced
and extensively substituted pyrrole rings, surrounding a single
cobalt atom (Co).
• Similar to porphyrins, but differ in two of pyrrole rings. Rings I
and IV are joined directly.
• Below the corrin ring system, is DBI ring (–5, 6- dimethyl
Benzimidazole riboside connected to:
At one end, to central cobalt atom
At the other end from the riboside moiety to the ring IV of
corrin ring system.
• A PO4 connects ribose to aminopropanol (esterified), in turn
attached to propionic acid of ring IV.
• A cyanide is coordinately bound to the cobalt -
cyanocobalamine.

31. Various forms of vitamin B12
• If 'R' group is cyanide (CN) then that form of vitamin B12 is called as
cyanocobalamin.
• If 'R' group is hydroxyl (-OH) then that form of vitamin B12 is called
as hydroxycobalamin.
• If the 'R' group is methyl (-CH3) then that form of Vitamin B12 is
called as methylcobalamin.
• If the 'R' group is deoxyadenosine then that form of vitamin Bl2 is
called as deoxyadenosylcobalamin.

32. Biologically active forms
• are cobamide coenzymes
Metabolic role of Cobamide Coenzymes
• Conversion of Methyl malonyl-CoA to succinyl-CoA: isomerase
• Methylation of Homocysteine to Methionine: Requires
tetrahydrofolate.
• Methylation of pyrimidine ring to form thymine.
• Importance in DNA synthesis: Conversion of ribonucleotides to
deoxyribonucleotides
• Required for metabolism of Diols
• In bacteria interconversion of glutamate and β-methyl aspartate:

33. Clinical significance of Vitamin B12 deficiency diseases
• Affects bone marrow, intestinal tract and neurological systems.
• Systems are affected because DNA synthesis, methionine synthesis and
fatty acid synthesis are altered.
• Due to inactive methionine synthase formation FH4 from methyl FH4 is
blocked.
• All the FH4 is trapped as methyl-FH4 (folate trap).
• Since FH4 is required for DNA synthesis, erythropoiesis and
gastrointestinal cells are affected.
• Bone marrow contains more megaloblasts.
• This megaloblastosis leads to anaemias.
• Since methionine synthesis is blocked due to inactive methionine synthase,
formation of phospholipids and neurotransmitters is impaired.
• As a result neurological system is affected.
• Methyl malonyl-CoA and propionyl-CoA accumulates due to block in
mutase action.
• Excess propionyl-CoA is diverted to odd number fatty acid synthesis which
is incorporated into membranes of nervous tissue.
• Normal fatty acid synthesis is affected due to inhibition of acetyl-CoA
carboxylase by methyl malonyl CoA.
• This disturbs the normal structure and function of nerves.

35. PANTOTHENIC ACID (VITAMIN B5)
• Consists of β-alanine in peptide linkage with a dihydroxy dimethyl
butyric acid (‘Pantoic’ acid).
• β-alanine + Pantoic acid → Pantothenic acid

36. Biological “Active” Form
• Is coenzyme A
Biochemical functions of pantothenic acid
• Formation of active acetate (Acetyl-CoA): Combines with acetate to
form Acetyl-CoA.
O
||
CH3—C ~ S. CoA
• Sulphur bond is a high energy bond

37. The active form participates in important metabolic reactions:
• Combines with oxaloacetate (OAA) to form citric acid, to initiate
TCA cycle.
• Acetylcholine formation.
• For acetylation reactions.
• Synthesis of cholesterol.
• Formation of ketone bodies.
• Acetyl-CoA and Malonyl-CoA are used in the synthesis and
elongation of fatty acids.
• Formation of Succinyl-CoA: Product of oxidative decarboxylation
of α-ketoglutarate
Succinyl-CoA is involved in:
Haem synthesis: It with glycine to form δ-ALA, the first step in
the pathway.
Degradation of ketone bodies by extrahepatic tissues:

38. Role in lipid metabolism:
• β-oxidation: First step involves the activation of the FA by formation
of CoA.
• Biosynthesis of FA: Pantothenic acid is a constituent of:
“Acyl-carrier protein” (ACP)
“multienzyme complex” in mammals, used in the
extramitochondrial de Novo fatty acid synthesis.
Role in Adrenocortical function:
Involved in the formation of adrenocortical hormones from acetyl
CoA and cholesterol.
Activation of some amino acids involve CoASH:
Occur among the branched chain amino acids such as valine and
leucine.

39. 2. VITAMIN C (ASCORBIC ACID)
• Is a sugar acid known as hexuronic acid.
• Is easily oxidized by atmospheric O2 to dehydroascarobic acid.
• High temperature (cooking) accelerates oxidation.
• Light and alkali also promotes oxidation.

40. Biochemical functions of vitamin C
• Act as antioxidant.
It is free radical scavenger.
Since it is a strong reducing agent it protects carotenes, vitamin E
and other B vitamins of dietary origin from oxidation.
• Required for the hydroxylation of proline and lysine residues of
collagen.
Since collagen is component of ground substance of capillaries,
bone and teeth, vitamin C is required for proper bone and teeth
formation also.

41. • Participates in hydroxylation reactions of steroid biosynthesis.
• Required for catecholamine synthesis from tyrosine.
• In the liver bile acid synthesis requires ascorbic acid.
• Participates in the synthesis of carnitine.
• Required for the absorption of iron in the intestine.
• Required in tyrosine catabolism.
• In large doses it reduces severity of cold.
• Effective in controlling bacterial invasion by inhibiting activity of
bacterial hyaluronidase enzyme

42. Clinical significance of Vitamin C deficiency diseases
• In adults it causes scurvy - but rarely occurs in normal people.
Symptoms of scurvy include:
Haemorrhages in various tissues particularly inside of thigh and
forearm muscles which may be due to capillary fragility.
General weakness and anaemia.
Swollen joints, swollen gums and loose tooth.
Susceptible for infections.
Delayed wound healing.
Bone fragility and osteoporosis.
• In infants, it gives rise to infantile scurvy. It occurs in weaned infants
who are fed on diets low in vitamin C.