This document provides an overview of the B complex vitamins, focusing on Thiamine (B1). It discusses the chemistry, functions, deficiency symptoms, and recommended daily intake of Thiamine. Key points include: Thiamine acts as a coenzyme (Thiamine Pyrophosphate) and is important for energy metabolism. Deficiency can cause Beriberi, with symptoms of weakness, edema, and nerve damage. Good sources include whole grains, yeast, and the aleurone layer of cereals.

1. The B Complex
Vitamins

2. Overview of Water-Soluble Vitamins
• Dissolve in water
• Generally readily excreted
• Subject to cooking losses
• Function as a coenzyme
• Participate in energy metabolism
• Marginal deficiency more common

3. B Complex Primary Functions
• Energy metabolism
– Thiamin (B-1), Riboflavin (B-2), Niacin (B-3),
Pyridoxine (B-6), Biotin, Pantothenic Acid
• Red blood cell synthesis
– Folate, B12
• Homocysteine metabolism
– Folate, B12, B6

4. VITAMIN B-COMPLEX
B1- Thiamine B7 – Biotin
B2- Riboflavin Panthothenic acid
B3- Niacin B9 – Folic acid
B6 – Pyridoxin B12- Cobalamin
VITAMIN-B1(Thiamine):
• it is anti beri beri or antineuritic vitamin
• Active or Co enzyme form: Thiamine Pyro Phosphate(TPP)
• Source: Aleurone layer of cereals (protein rich layer) is a rich
source of Thiamine.
• Whole wheat flour, unpolished handpound rice have a better
nutritive value than completely polished rice. Yeast is also a good
source of Thiamine.

5. Chemistry of Thiamine(Pyrimidine + methylene bridge+Thiazole):
• It contains a pyrimidine ring connected to a thiazole ring by
means of methylene bridge. (pyrimidine – methylene bridge –
Thiazole)
• The Vitamin is converted to its active co-enzyme form by
addition of two phosphate groups with the help of ATP. This is
catalyzed by Thiamine pyrophospho transferase. (
Thiamine + PP )
TPP transferase
Thiamine pyro phosphate (TPP)

6. Physiological role of Thiamine:
1. The co-enzyme form of Thiamine is thiamine pyro phosphate
is essential for activation of Pyruvate DeHydroganase
PDH, TPP
Eg: Pyruvate -------------- Acetyl CoA + CO2
2. TPP is used as co-enzyme in the oxidative decarboxylation of
alpha keto glutarate to succinyl CoA and CO2(steps in TCA
cycle).

8. 3. For the activation of Transketolase (enzyme of HMP shunt)
4. TPP has a main role in carbohydrate metabolism
5. TPP plays a important role in the transmission of nerve
impulse
– Provide energy to the brain.
– Improve transmission of nerve impulses
– Proper function of the heart muscles.
– Healthy mucus membrane.
– Maintenance of smooth and skeletal muscles.
– Formation of RBC’s.

9. • DEFICIENCY MANIFESTATION OF THIAMINE :
BERI-BERI(Weakness):
Symptoms: anorexia (loss of appetite),weakness, constipation,
nausea, mental depression, peripheral neuropathy, pins and
needles sensations complaints in legs .
WET BERI-BERI:
• Edema of legs, face, trunk and serous cavities
• Cardio-vascular manifestations are prominent.
• Palpitation, breathlessness
• Distended neck veins
• Abnormal BP
• Finally death occurs due to heart failure.
DRY BERI-BERI:
• Peripheral neuritis with sensory
disturbances leads to complete
paralysis.
• Edema is not seen.
• Muscles become weak and Difficulty
in Walking .
• CNS manifestations are the main
features.
• It is otherwise called mixed beri beri

10. INFANTILE BERI-BERI:
This occurs in infants born to mothers suffering from thiamine
deficiency.
• Restlessness
• Sleeplessness
• Vomiting
• Convulsions and death may occur suddenly due to cardiac failure.
CEREBRAL BERI-BERI (WERNICKE- KORSAKOFF
SYNDROME)
this disorder mainly due to
1. chronic alcoholics.
2. Insufficient intake or
3. Impairment of absorption of thiamine will lead to this syndrome. It
is characterized by loss of memory, apathy and fromotion of the
eye ball

11. • BIOCHEMICAL PARAMETERS:
1. Blood thiamine is reduced.
2. Pyruvate alpha KG and lactate are increased.
3. Erythrocyte trans ketolase activity is reduced.
• RECOMMENDED DAILY ALLOWANCE:
1 to 1.5mg/day
Antagonist:
Pyrithiamine and oxythiamine

13. VITAMIN B2 (Riboflavin)
• It is a water soluble vitamine and takes part in variety of oxidation
reduction reactions
• Riboflavin is orange-yellow fluorescent compound
• Source of Riboflavin : Milk, Liver, Dried yeast, Egg are rich
sources.
Fish, whole cereals, legumes and green leafy vegetables are good
source.
• STRUCTURE OF RIBOFLAVIN:
It has 6,7 di-methyl iso-alloxazine ring( a hetero cyclic 3 ring
structure) to which a ribitol is attached.
Active form: FMN(Flavin Adenine Mononucleotide)
FAD (Flavin Adenine Dinucleotide).
Riboflavin FMN
ATP ADP
FMN FAD
ATP PPi

14. dimethylisoalloxazine
ring system linked to
ribose
N
N
N
N
H3C
H3C
O
C
O
H
C
H
H
C
H OH
C
H2C
H OH
H OH
OH
RIBOFLAVIN

15. coenzymes are involved:
FMN, riboflavin phosphate (flavin
mononucleotide)-coenzyme for Warburg yellow
enzyme, Cytochrome C reductase & L a. a
dehydrogenase.
 flavin adenine dinucleotide (FAD)
Contains 2 phosphate groups, adenine, ribose &
ribitol. It is the prosthetic grp for diaphorase, D
amino acid dehydrogenase, glycine oxidase,
Xanthine oxidase, and Acyl coA dehydrogenase.

16. Structures of FMN & FAD

17. •Biochemical Functions ( involved nearly150 reaction) .
• It is involved in the metabolism of carbohydrates, fats and proteins
• Acts as a coenzyme for several enzyme systems involved in
hydrogen transfer reactions- flavoproteins
•It acts as hydrogen carriers in the respiratory chain(ETC)
•Involve in many redox reactions ( oxidation – reduction reaction)
• for the activation of B12 and folate
•Protect RBC and other cells from oxidative stress
•ENZYMES USING RIBOFLAVIN COENZYMES
FAD :NADH dehydrogenase FMN : L amino acid oxidase
Cytochrome reductase
succinate dehydrogenase
d -amino acid oxidase
pyridoxine-5-phosphate oxidase
glutathione reductase
Xanthine oxidase

18. • MANIFESTATION :
Symptoms are confined to skin and mucous membrane.
• Glossitis (tongue smooth and purplish)
• Magenta colored tongue
• Cheilosis (dry scalling of lips, espicially in the corner of mouth)
• Angular stomatitis (generalised inflammation on oral mucosa),
mouth ulcers
• Circum corneal vascularization(invasion of new blood vessel into the
cornea)
• DAILY REQUIREMENT:
Adults on sedentary work require about 1.5mg/day
During pregnancy lactation and old age requirement is between
and 1.7 and 2.1mg/day

22. NIACIN (Vit.B3)- Pellagara Preventing Factor
• Active form:
NAD & NADP (Nictonamide Adenine Dinucleotide) and it is synthesized from
tryptophan
• SOURCES:
Dried yeast, rice polishing, liver, peanut, whole cereals, legumes, meat and fish
are rich sources.
Tuna(fish) is one of the best source
About half the requirement is met by the conversion of Tryptophan to Niacin.
• CHEMISTRY OF NIACIN:
Niacin is derivative of pyridine and it is pyridine 3 carboxylic acid.
Niacin + Amide = Nictonamide
• CO ENZYME FORMS OF NIACIN:
Niacin is converted into its co-enzyme forms viz.,
NAD+ and NADP+.

23. Biochemical functions
• It mainly involved in oxidation reduction reaction
• Essential for O2 transport in Electron Transport chain
• 1. Lactate dehydrogenase requires NAD+ as coenzyme in the
conversion of lactate to pyruvate (anaerobic Glycolysis). One
NADH molecule is oxidized in the respiratory chain to
generate 2.5 ATP’s.
• Lactate pyruvate
• NAD NADH2
• 2. Alpha Keto glutarate dehydrogenase also requires NAD+ as coenzyme
in the conversion of Alpha Keto glutarate to succinyl CoA(TCA Cycle).
(Both B1 and B3 are act as co enzyme for AKGDH)
• αKG succinyl coA
• NAD NADH2

24. 3. Glucose-6-phosphate dehydrogenase requires
NADPH as coenzyme in the conversion of Glucose-6-
Phosphate  6-phospho-gluconolactone in HMP
SHUNT
4. Malic enzyme also requires NADPH as coenzyme
in the conversion of Malate to pyruvate in
gluconeogensis.

26. • NIACIN DEFICIENCY:
Pellagra ( rough skin):
• It is characterized by three symptoms. The symptoms of pellagara
are commonly referred as 3D(Dermatitis, Diarrhoea and
Dementia)
1.Dermatitis
bright red erythema (redness of skin) occurs in feet, ankles
and face in early stages.
(b) Increased pigmentation around the neck occurs - casal’s
necklace.
2. Diarrhoea
may be mild or severe with blood and mucus resulting in weight
loss.
(b) Nausea and vomiting may also be present.

28. 3. (a) Dementia – it is associate with degeneration of
nerve tissue and the symptoms are anxiety,
irritability, poor memory and sleepness(insomnia)

29. • Factors causing Niacin deficiency:
1. Dietary deficiency of tryptophan
Niacin is synthesized from tryptophan
Pellagra is seen among people whose staple diet is
maize and sorghum (jowar or guinea corn).
sorghum contains leucine in high quantities which
inhibits QPRT (Quinolinate Phospho Ribosyl
Transferase) and hence Niacin cannot be converted to
NAD+

30. 2. Lack of synthesis
Kynureninase, an important enzyme(pyridoxal
phosphate dependant) in the pathway of
tryptophan. Hence, conversion of tryptophan to
niacin is not possible in pyridoxal deficiency.
3. Isoniazid- This anti-tuberculosis drug inhibits
pyridoxal phosphate formation blocking the
conversion of tryptophan to NAD+

31. 4. HARTNUP DISEASE:
It is an inherited disease.
Absorption of tryptophan is defective. Hence,
tryptophan is excreted through urine in large
quantities. This leads to lack of tryptophan and
consequently deficiency of nicotinamide.
5. CARCINOID SYNDROME:
It is type of cancer in gastrointestinal tract and lungs
In this disease the tumor utilizes major portion of
available tryptophan for serotonin synthesis making
tryptophan unavailable.

32. • RECOMMENDED DAILY ALLOWANCE:
Normal requirement is 20mg/day.
During lactation requirement is 25mg/day
• THERAPEUTIC USE OF NIACIN:
(a) Nicotinic acid when given orally or parenterally
produces vasodilatation of the cutaneous vessels and
histamine release.
The reaction is accompanied by itching, burning and
tingling.
(b) Nicotinic acid inhibits the mobilization of free fatty
acids from adipose tissue thus reducing acetyl CoA
pool. Hence, serum cholesterol is lowered.

36. VITAMIN B6 (Pyridoxine)
• CHEMISTRY:
• Vitamin B 6 refers to
• Pyridoxine ---------alcohol (mostly in vegetables)
• Pyridoxal ----------aldehyde} mostly in animal
products
• Pyridoxamine -----amine } “ “ “ “
• Active form : pyridoxal phosphate synthesized
from Pyridoxal by Pyridoxal kinase using ATP.
• FUNCTIONS: PLP acts as co-enzyme for many
reactions in amino acid metabolism.

38. N
CHO
CH2OH
HO
H3C N
CH2NH2
CH2OH
HO
H3C
PYRIDOXAMINE
PYRIXOXAL
N
CH2OH
CH2OH
HO
H3C
PYRIDOXINE
Collectively, pyridoxine, pyridoxal and
pyridoxamine and their phosphates are
known as vitamin B6

39. Pyridoxal phosphate
Biochemical functions:
1. Decarboxylation of amino acids
2. Transaminase reactions
3. Synthesis of heme
4. Transulfuration reactions
5. Conversion of Tryptophan to niacin(B3)
6. Conversion of linoleic acid into arachidonic acid
(prostaglandin precursor)
7. Formation of sphingolipids

40. 1. Transamination: These reactions are catalyzed by amino
transferases using PLP as coenzyme.
Alanine transaminase
Alanine + α KG -------------------- Pyruvate + Glutamate
PLP
Aspartate transaminse also require PLP as their coenzyme for its
activity
PLP involve in the conversion of aminoacid to keto acid
• 2.Decarboxylation :
All decarboxylation reactions of amino acids require PLP as
coenzyme. Eg: Glutamate- GABA
• GABA is an inhibitory neuro transmitter (inhibits the
transmission of nerve impulse) and so responsible for
many sedative and depressive action in brain.
• Histidine -  Histamine
Histamine is a mediator of allergy, vasodilator and lowers BP
Tryptophan  Serotonin(neuro transmitter responsible for
sleep, behavior, blood pressure etc..,

41. • Synthesis of catecholamines require PLP
(dopamine, norepinephrine and
epinephrine) which involved in nerve
regulation

42. • Homocysteine is correlated with myocardial
infarction. Therefore, pyridoxine is used in
clinical practice to prevent CAD in
homocysteinemia
• 4. ALA(Amino Levolinic Acid) synthase is a
PLP dependant enzyme. It catalyzes the rate
limiting step in heme biosynthesis. Hence, in Vit
B6 deficiency, anemia may be seen.

43. • 5. PRODUCTION OF NIACIN:
Pyridoxal phosphate is required for the
synthesis of Niacin from Tryptophan.

44. • 6. GLYCOGENOLYSIS:
Phosphorylase enzyme which is
involved in the breakdown of glycogen to
glucose-1-phosphate requires PLP. In Vit
B6 deficiency glycogen breakdown is
inhibited.

45. • DEFICIENCY MANIFESTATION OF PYRODOXINE:
1.NEUROLOGICAL MANIFESTATIONS:
In Vit B6 deficiency, PLP dependant enzymes function
poorly. Hence, serotonin, epinephrine, nor-adrenaline
and GABA are produced poorly. Therefore
neurological symptoms are quite common. In
children Vit B6 deficiency leads to convulsions due to
decreased formation of GABA.

46. • PLP is also involved in the synthesis of
sphingolipids. Therefore Vit B6 deficiency leads
to demyelination of nerves and consequent
peripheral neuritis.

47. 2. DERMATOLOGICAL MANIFESTATIONS:
Vit B6 deficiency leads to Niacin deficiency
since niacin is synthesized from tryptophan
require PLP. Hence, pellagra which is one of the
dermatological manifestations of niacin deficiency
occur in Vit B6 deficiency also.
3. HAEMATOLOGICAL MANIFESTATIONS:
Hypo chromic microcytic anaemia may occur
due to the inhibition of heme biosynthesis.(ALA is
a rate regulating enzyme(PLP depend) of heme
synthesis)
The metabolic disorders which respond to
Vit B6 therapy are xanthurenic aciduria.

49. • EFFECT OF DRUGS:
1. IsoNiazid: It is an anti-tuberculosis drug
and it inhibits pyridoxal kinase, reducing the
formation of PLP. This results in Vit B6
deficiency.
2. Oral contraceptives: Mild Vit B6 deficiency
may be seen in women taking oral
contraceptive pills.
3. Ethanol: Ethanol is converted to
acetaldehyde which inactivates PLP. Hence,
Vit B6 deficiency leads to neuritis.

52. • DIETARY SOURCE: Yeast, rice polishing,
wheat germs, cereals, pulses, oily seeds,
egg, milk, fish, meat and green leafy
vegetables.
• REQUIREMENT (RDA):
1 to 2 mg per day in normal adults.
2.5mg per day in pregnancy and lactation
Vit B6 requirement is related to protein
intake.
• TOXICITY OF VIT B6: Doses over 100mg
may lead to imbalance, numbness (sensation
of burning pricking of skin ), muscle
weakness and nerve damage.

53. PANTOTHENIC ACID(B5)
• The Greek word “Pantos” means every
where i.e., it is widely distributed in nature.
• CHEMISTRY: Pantothenic acid contains
β-Alanine and D-Pantoic acid in amide
linkage.

55. • a yellow viscous oil (free acid)
• stable to moist heat (not to dry heat) and to oxidizing and
reducing agents
Active forms
• Activated form : coenzyme A or Co A (panthothenic acid+
cysteine +ADP)
• COASH
• acyl carrier protein (ACP)
• Co A is essential for the metabolism of carbohydrates, fats
and Protein. About 70 enzymes require Co A as co enzyme.
• Co A combines with the metabolites at SH grp of
Pantotheine(B5 analogue) through a high energy sulfur
bond.
• Acyl carrier protein:
• Pantothenic acid combines with protein to form Acyl carrier
protein. ACP is the coenzyme for fatty acid synthesis.

56. Synthesis of co enzyme A

57. •
Physiological role of Coenzyme A
( CoA .SH)
Coenzyme A + acetate  active acetate in the form of acetyl
co A- Acetyl Co A is essential for the following metabolic
reactions:
• Acetyl Co A from fat, carb, and proteins combines with
oxalo acetate to form Citric acid , which enters TCA for
complete oxidation to CO2 and H2O.
• Acetyl Co A combines with choline to form Acetyl choline a
neurotransmitter in autonomic nervous system (cholinergic)
and in the brain.
• Detoxification of certain drugs like sulfonamide

58. •Acetyl Co A is the precursor for synthesis of
ketone bodies and cholesterol which forms
steroid hormones.
•CoA is also associated with succinate to form
succinyl Co A + glycine to form Heme.
• Fatty acids are activated to acyl CoA before
oxidation
• Acetyl Co A is the precursor for synthesis of
bile salts
• Activation of branched chain amino acids,
Valine & iso Leucine.

59. • DEFICIENCY OF PANTOTHENIC ACID:
“Dr.Gopalan’s burning foot “syndrome is manifested as ‘
Parasthesia’ (burning, lightning pain) in lower extremities
and sleep disturbances.
• This syndrome is seen in chronic alcoholics and in some
renal dialysis patients
• Apathy (lack of intrest)
• Fatigue
• Improper synthesis of acetyl choline
• Fatigueue (tiredness, fatig ue can be allleviated by
periods of rest)
• GIT disturbances
• .

60. • SOURCES :
Widely distributed in plants and animals.
Also synthesized by normal bacterial flora in the intestine.
Yeast , liver and eggs are rich sources. Deficiency is very
rare.
• REQUIREMENT ( RDA):
• Normal adult 7mg/day
pregnant and lactation 8mg/day

61. BIOTIN
• Biotin is also known as ‘anti-egg white injury factor’.
• An imidazole sulfur containing compound
• referred to as vitamin B7 or vitamin H
• CHEMISTRY: It consists of an imidazole ring fused with
a thiophene ring with a valeric acid side chain.
• Active form: carboxy biocytin enzyme complex
• Biotin + enzyme biocytin + HCo3 carboxy biocytin
• CO ENZYME ACTIVITY OF BIOTIN:
• biochemical role: carbon dioxide fixation
• two step process:
1. Binding of CO2 to biotin –
N-carboxybiotin
2. Transfer of CO2 to a substrate
– Activation of biotin requires enzyme, CO , ATP and Mg++

62. Biotin
N
N
S
O
H H
H
H
(CH2)4-COOH
BIOTIN
Imidazole ring fused with thiophene ring
with valeric acid side chain

63. • BIOTIN REQUIRING CO2 FIXATION REACTIONS:
1. Acetyl CoA carboxylase:
Biotin adds CO2 to Acetyl CoA to form malonyl CoA.This is the
rate limiting reaction in the biosynthesis of fatty acids.
Acetyl CoA + CO2+ ATP--- Melonyl CoA + ADP + PI
2. Pyruvate carboxylase:
Pyruvate + CO2+ ATP --- Oxalo acetate + ADP + PI
This reaction is important in two aspects. One, it provides oxalo
acetate which is the catalyst for TCA cycle. Second, it is an
important enzyme in the gluco neogenic pathway.
3. Propionyl co A carboxylase
Propionyl co A methyl malonyl coA
4. Carbomyl phosphate synthase (Urea cycle)

64. • BIOTIN ANTAGONIST:
Avidin, a protein present in egg white has
great affinity to Biotin and it tightly bound
with biotin and prevent it absorption.
Hence, intake of raw egg may cause Biotin
deficiency.
Avidin is heat labile and boiling of egg will
neutralize the inhibitory activity. Egg yolk
contains Biotin.

65. • DEFICIENCY OF BIOTIN :
Prolonged use of anti-bacterial drugs may result
in Biotin deficiency.
Biotin deficiency symptoms include dermatitis,
atrophic glossitis (swelling of tongue),
hyperesthesia(abnormal increase in sensitivity in
skin ), muscle pain and anorexia( loss of
appetite) hair loss (in some condition)
intramuscular dysfunction.

66. • REQUIREMENT OF BIOTIN:
200 to 300mg/day
• SOURCES :
Normal bacterial flora of the gut provides
adequate quantities of Biotin. It is widely
distributed in plant and animal tissues.
Liver ,Yeast, peanut, soyabean, milk
and egg yolk are rich sources.

67. Biotin-dependent enzymes:
Pyruvate carboxylase (synthesis of oxaloacetate for
gluconeogenesis and replenishment of the citric
acid cycle)
Acetyl CoA carboxylase (fatty acid biosynthesis)
Propionyl-CoA carboxylase
b-methylcrotonyl-CoA carboxylase
holocarboxylase synthase (multiple carboxylase)
Biotin antagonist:
Desthiobiotin, biotin sulphanilic acid
Extra: intake raw eggs leads to iching dermatitis which is called raw
egg white injury which prevent by Biotin

68. FOLIC ACID(B9)
• The term ‘FOLIUM’ (latin ) means leaf of vegetable. Folic acid
is abundant in vegetables.
• It also obtained by yeast
• Other common name(s): folate, folacin, vitamin B9 vitamin M
• Vitamin B9 (folic acid and folate) is essential for numerous bodily
functions. Humans cannot synthesize folate de novo; therefore,
folate has to be supplied through the diet to meet their daily
requirements.
• The human body needs folate to synthesize DNA, repair DNA, and
methylate DNA as well as to act as a cofactor in certain biological
reactions.[7]It is especially important in aiding rapid cell
division and growth, such as in infancy and
pregnancy. Children and adults both require folic acid
to produce healthy red blood cellsand prevent anemia.[8]
• CHEMISTRY: Folic acid is composed of three constituents.
Pteridine + PABA to form pteroic acid. This is attached to glutamic
acid to form pteroyl glutamic acid or folic acid. Initially folic acid is in
oxidised form. But reduced form is only active form
• Active co enzyme form is 5,6.7,8 tetrahydrofolic acid

70. • ABSORPTION OF FOLIC ACID: It is readily absorbed by
upper part of jejunum it is transported by beta globulins. It
is taken up by the liver where the co-enzymes are
produced.
• CO ENZYME FUNCTIONS OF FOLIC ACID:
Folic acid is first reduced to 7,8 di-hydro
folic acid and then to 5,6,7,8 tetra-hydro
folic acid. Both reactions are catalyzed by
NADPH dependant folate reductase.

72. • BIOCHEMICAL FUNCTIONS: carrier of one carbon groups (
organic moles containing a single carbon)
• It actively involved in one carbon metabolism
• It acts as acceptor or donor of one carbon units in variety of
reaction involving in protein and nucleic acid metabolism
• These one carbon grp is attached to the 5th or 10 th or both 5th
and 10 th nitrogen atom of THFA so it is otherwise folinic acid
• N 5 methyl THFA is required for the synthesis of methionine
which takes part in transmethylation reactions for synthesizing
choline, epinephrine,creatin etc.
• The following groups are one carbon compounds.
1. Methyl (-CH3)
2. Methylene( -CH2-)
3. Methenyl (-CH=)
4. Formyl (CHO
5.. Formimino (- CH = NH)

73. • Biochemical functions
– one carbon fragment transfer (formyl, methyl,
hydroxymethyl)
• conversion of homocysteine to methionine
• conversion of serine to glycine
• It also involved in synthesis of ethanolamine and choline
• synthesis of thymidylic acid: the synthesis of dTMP (2'-
deoxythymidine-5'-phosphate) from dUMP (2'-
deoxyuridine-5'-phosphate). Which is essential for DNA
repair and DNA synthesis
• synthesis of purines (de novo) 2 & 8 C formation
• Involve in proper synthesis of neural tube which is very
essential for the formation of brain and spinal cord

74. • DEFICIENCY MANIFESTATIONS:
Common symptoms of folate deficiency include
diarrhea, macrocytic anemia with weakness or shortness of
breath, nerve damage with weakness and limb numbness
(peripheral neuropathy),[11] pregnancy complications, mental
confusion, forgetfulness or other cognitive declines, mental
depression, sore or swollen tongue, peptic or mouth ulcers,
headaches, heart palpitations, irritability, and behavioral
disorders. And also..
1. Reduced DNA synthesis and cell growth is reduced

75. 2. Macrocytic Anaemia:
Most characteristic feature of folate deficiency
.
(a) During RBC generation DNA synthesis is
delayed and protein synthesis is continued.
Thus haemoglobin accumulates in RBC hence it
seen abnormally large in size
(b) Reticulo cytosis is often seen. These abnormal
RBC’s are destroyed in spleen. This haemolysis
leads to reduction of life span of RBC. Reduced
generation and increased destruction of RBC’s
results in anaemia.
(c ) Leucopenia (abnormal lowering WBC in circulating blood)
and thrombocytopenia (decrease the number of platlets in
blood) are also manifested.

76. Histidine metabolism: Histidine is metabolised
to FIGLU which is intermediate during
conversion of histidine to glutamate. The
formimino grp is transferred to THF to
produce N5 formiminoTHF. But deficiency of
folic acid, cause the accumulation of
Formimino Glutamic acid.
In folic acid deficiency FIGLU is excreted in
urine.
Hyper Homocystenemia:
Elevated plasma levels of homocysteine are
associated with increased risk of
atherosclerosis, thrombosis and
hypertension. This complication is mainly due
to deficiency of folic acid which is essential for
the conversion of homocysteine to methionine

77. • 3.HYPER HOMOCYSTEINEMIA:
Increased Homocysteine levels in blood is seen (>15µmols/l)
which increases the risk of coronary artery disease.
• 4. BIRTH DEFECTS:
Folic acid deficiency during pregnancy leads to neural tube
defects in the fetus. Neural tube defects are birth
defects of the brain, spine, or spinal cord. They happen
in the first month of pregnancy, often before a woman
even knows that she is pregnant. The two most
common neural tube defects are spina bifida and
anencephaly. In spina bifida, the fetal spinal column
doesn't close completely. There is usually nerve
damage that causes at least some paralysis of the legs.
In anencephaly, most of the brain and skull do not
develop.
• 5. CANCER:

78. • ASSESMENT OF FOLIC ACID DEFICIENCY :
1. Histidine load test or FIGLU excretion test.
Folic acid is associated with Histidine metabolism
and produce FIGLU (For Imino Glutamate) which
essential for one carbon transfer. Incase of folate
deficiency FIGLU is accumulated and excreted
through urine.
2. AICAR (Amino Imidazole Carboxamide
Ribosyl) excretion: In purine ring biosynthesis
the last step is the addition of C2 with the help of
N-Formyl THFA. When this is blocked the
precursor amino imidazole carboxamide ribosyl-5-
phosphate accumulates and is excreted in urine.
3. Peripheral blood picture: Macrocytic anaemia

79. • SOURCES:
Yeast, Green leafy vegetables are rich sources , cereals, pulses, oil
seeds and egg are moderate sources. Milk is a poor source.
• RDA:
• adults: 400 - 500µg
• Chidren – 100 -300µg
• Lactation & pregnancy – 600 -800µg
• Plasma level – 2 - 5µg/ day
• FOLIC ACID THERAPY:
Therapeutic dose is 1mg of folic acid per day
Folic acid and Vit B12 are given in combination to patients
=macrocytic anaemia
Antagonist
Aminopterine, amethopterine, trimethoprin and sulfanamide

80. • FOLATE ANTAGONIST:
1. Sulphonamides: They are
structurally similar to PABA. Hence,
competitively inhibit the enzyme
responsible for the incorporation of
PABA into di-hydro-pteroic acid which
is precursor of folic acid. Bacteria can
synthesize folic acid from the
components Pteridine, PABA and
Glutamate.

81. • When sulphonamides are given such
micro organisms cannot synthesize folic
acid and hence their growth is inhibited. As
man cannot synthesize folic acid the entire
molecule has to be supplied in the diet.
Preformed folic acid also cannot enter the
bacteria. Thus sulphonamides act as very
good anti-bacterial agents.

82. • 2. Pyrimethamine: This is an anti-
folate agent used against plasmodial
infections especially as anti-malarial
drug.
• 3. Aminopterine & Amethopterin:
Aminopterine (4-amino folic acid) and
Amethopterin (4-amino 10-methyl folic
acid) are powerful inhibitors of folate
reductase and THFA generation. These
drugs inhibit DNA formation and cell
division. They are widely used as anti-
cancer drugs especially for leukemia.

84. VITAMIN B 12
• Vitamin B12 is the general name for cobalamins
and is found only in the foods of animal origin
• It is otherwise called anti pernicious anemia
vitamin
• It is the only vitamin that possesses a metal ion
(cobalt) as part of its structure
Source: Present in foods such as liver, fish, eggs, milk
• absent in vegetables and fruits

85. Co enzymatic form of B12:
Adenosylcobalamin
methylcobalamin
CHEMISTRY: It is a water soluble, heat stable and red
colored vitamin.
It contains 4% Cobalt by weight. 4 pyrrole rings coordinated
with a cobalt atom is called as ‘corrin ring’. The fifth
valency of cobalt is linked to a substituted benzimidazole
ring. This is then called Cobalamine. The sixth valency is
satisfied by one of the following groups cyanide, hydroxyl,
adenosyl or methyl. (Cobalt + 4 pyrrole ring = corrin ring,
Corrin ring + benzimidazole = cobalamine )
(cobalamine + cyanide = cyano cobalamine)
(cobalamine + hydroxyl = hydroxy cobalamine)

89. • CYANOCOBALAMINE: When cyanide is
added at R position the molecule is called
‘cyanocobalamine’ it has not physiological
functions. Oral preparations are in this
form.
• HYDROXY COBALAMINE: OH group is
attached at the R position. Injectable
preparations are in this form.
• ADENOSYL COBALAMINE: When taken
up by the cells these groups are removed
and deoxy andenosyl cobalamine is
formed. This is the major storage form
seen in liver.

90. • METHYL COBALAMINE: When methyl
group replaces adenosyl group methyl
cobalamine is formed. This is the major
form seen in blood circulation and in
cytoplasm of cells.
• Nitrocobalamine
• ADO –B12 & METHYL B12 are the
functional co enzymes in the body.

91. • ABSORPTION OF VIT B 12: Vit B12
combines with the intrinsic factor (a glycoprotein
released by parietal cells) in stomach. Hence,
B12 is otherwise known as Extrinsic factor
(EF).
Intrinsic factor, a glycoprotein of molecular
weight 50,000 is secreted by the gastric
parietal cells.
One molecule of IF combines with 2 molecules
of B12 and this complex is attached with
specific receptors on the mucosal cells and
internalized. B12 is absorbed from ileum
where as folic acid from jejunum

92. • TRANSPORT AND STORAGE:
In blood methyl cobalamine is
predominant. Trans cobalamine (TC1) a
glycoprotein is a specific carrier. B12 is
stored in liver cells as methyl cobalamine
and then it convert in to deoxy adnosyl
cobalamine
• Whole liver contains 2mg of Vit B12
which is sufficient for 2 to 3 years. Hence,
B12 deficiency is seen only years after
gastrectomy.

94. • FUNCTIONAL ROLE OF VIT B12:
1. Methyl malonyl CoA isomerase:
Methyl malonyl CoA is converted to succinyl
CoA by enzymes methyl malonyl CoA mutase
which require Ado-B12 for its activation.
succinyl coA which then enter to TCA cycle
and it is also essential for the synthesis of
heme
In B12 deficiency methyl malonyl CoA does
not undergo further changes and hence
excreted in urine (methyl malonic aciduria)

95. 2. Synthesis of methionine from homo cysteine
The conversion of methyl THFA to THFA and the
conversion of Homocysteine to methionine need the
activity of Vit B12 (methyl cobalamine).
Homocysteine methyl transferase
Homocysteine Methionine
B12
The above metabolic step signifies the interrelationship
between B12 and folic acid
apart from above, B12 require for conversion of
Uracil to thymine
aminoethanol to choline
activation of amino acids for protein synthesis

96. • METHYL FOLATE TRAP & FOLATE
DEFICIENCY: The production of methyl
THFA is an irreversible step and the only
way for generation of free THFA is from
methyl THFA. Therefore, when Vit B12 is
deficient this reaction cannot take place
and this is called ‘methyl folate trap’ and
leads to cause deficiency of folic acid

97. • CAUSES OF VITAMIN B12 DEFICIENCY:
1.NUTRITIONAL DEFICIENCY:
It is common amongst vegetarians of low socio
economic growth. Only source of Vit B12 in
vegetarian diet is curd or milk & lower income group
may not be able to afford it.
2. DECREASED ABSORPTION :
Absorptive surface is reduced by gastrectomy,
resection of ileum and malabsoprtion syndrome.
3. ADDISONIAN PERINICIOUS ANAEMIA:
It is an auto immune disease with a strong familial
back group in persons >40 years of age. Antibodies
are generated against IF and its destroyed. so IF
becomes deficient leading to defective absorption of
Vit B12.

98. • 4. GASTRIC ATROPHY:
Atrophy of gastric epithelium leads to IF deficiency
and decreased B12 absorption. In chronic iron
deficiency anaemia there is generalized mucosal
atrophy. In 40% of cases of iron deficiency anaemia
super added gastric atrophy is seen.
• 5. PREGNANCY:
Increased requirement in pregnancy is another
cause for Vit B12 deficiency.
• 6. FISH TAPE WORM:
it is common in Scandinavian countries where
eating live fish is a delicacy. This fish has special
affinity to B12 causing reduction in available vitamin
B12.

99. • DEFICIENCY MANIFESTATIONS:
1. FOLATE TRAP: Vit B12 deficiency causes simultaneous folate
deficiency due to folate trap. Therefore, all manifestations of
folate deficiency is also seen in Vit B12 deficiency.
2. MEGALOBLASTIC ANAEMIA: Megaloblast and immature
RBC’s are observed in peripheral blood.
3. Pernicious anemia:
most important disease associated with vitB12 deficiency is
pernicious anemia. And It is an auto immune disease with a
strong familial back group in persons >40 years of age.
Antibodies are generated against IF and it got destroyed. so IF
becomes deficient leading to defective absorption of Vit B12.
.

100. it is charecterized by low hemoglobin levels, decreased the
number of erythrocytes and neurological manifestations
• Auto immune destruction of gastric parietal cells
4. ABNORMAL HOMOCYSTEINE LEVELS:
The conversion of Homocysteine to methionine requires
Vit B12. In B12 deficiency this step is blocked leading to
homocysteinemia. Homocysteine is related to myocardial
infarction. Hence, B12 and folic acid are protective
against ischemic heart disease

101. • 4. DEMYELINATION OF NERVES :
The conversion of S-adenosyl methionine
to S-adenosyl homocysteine liberates
methyl group. This methyl group is used
for the methylation of phosphatidyl
ethanolamine to phosphatidyl choline. In
B12 deficiency liberation of methyl group
is inhibited and hence phosphatidyl
choline formation is suppressed. This
leads to deficient formation of myelin
sheath of nerves, demyelination and
neurological lesions.

102. • 5. SUBACUTE COMBINED DEGENERATION :
Damage to nervous system is seen in Vit B12
deficiency but not in folate deficiency. There is
demyelination affecting cerebral cortex and spinal
cord. Since both sensory and motor tracts are
affected it is named as ‘combined degeneration’.
Altered reflexes , loss of position sense,
unsteadiness in gait, positive Romberg’s sign(
falling when eyes are closed) and positive
Babinski’s sign (plantar reflex) are seen.
• 6. ACHLORHYDRIA:
Absence of acid in gastric juice is associated with
Vit B12 deficiency.

103. • ASSESMENT OF VIT B12 DEFICIENCY:
1. Serum B12. is quantitated by RIA or ELISA.
2. Schilling Test: Radioactive labelled Cobalt
60 Vit B12 1mcg is given orally in gastric
atrophy there is no absorption and hence the
entire radioactivity is excreted in faeces and
radioactivity is not observed in liver.
In nutritional deficiency there will be
enhanced absorption and therefore
radioactivity is noted in liver region with very
little excreted in fasces.

104. 3. Methyl malonicaciduria is present.
4. FIGLU excretion test
5. Peripheral smear- peripheral blood and
bone marrow morphology shows
magalobalstic anaemia.
6. Homocysteineuria.

105. • TREATMENT :
If magalobalstic anaemia is treated with
folic acid alone anaemia may improve
but associated nervous lesions are
aggravated. Hence, all macrocytic
anaemias are treated with folate and
Vit B12.

106. VITAMIN - C
• CHEMISTRY:
Vitamin C is water soluble, easily destroyed
by heat, alkali and storage.
70% of Vit-C is lost by cooking. The structural
formula closely resembles that of
carbohydrates. The strong reducing property
of this Vitamin depends on the double
bonded carbons ( enediol form).
Only L-Ascorbic acid and Dehydro ascorbic
acid have anti-scorbutic activity. D-Ascorbic
acid has no activity.

107. • BIOSYNTHESIS:
Most animals and plants can synthesize ascorbic
acid from glucose.
Man, higher primates, guinea pigs and bats are the
only species which cannot synthesize ascorbic acid.
Therefore, it should be supplied in the diet.
• METABOLISM OF ASCORBIC ACID:
1. It is readily absorbed from GI tract. Since it is
water soluble it is excreted in the urine. It is a strong
reducing agent and reduces Benedict’s reagent.
2. Oxidation of ascorbic acid is dehydroascorbic acid
which is oxidized to oxalic acid. Ascorbic acid is
partly excreted unchanged and partly as oxalic acid.

108. 3. Ascorbic acid levels varies between 0.4 to
1.5mg/100ml plasma. A low level in blood is
noted in women taking contraceptive pills
and also in chronic alcoholics.
4. Very high concentration of Vit C is
observed locally in healing wounds. Vitamin
C is essential for would healing.

109. • BIOCHEMICAL FUNCTIONS:
1.REVERSIBLE OXIDATION REDUCTION:
Vit C can change between ascorbic acid and
dehydro ascorbic acid. Most of the physiological
properties could be explained by this redox
system.
• 2. HYDROXYLATION OF PROLINE AND
LYSINE:
Hydroxy proline and Hydroxy lysine are essential
for the formation of cross links in collagen which
gives tensile strength to the fibers. This process is
absolutely necessary for the production of
supporting tissues such as osteoid, collagen and
inter cellular cement substance.

110. • 3. TRYPTOPHAN METABOLISM:
Ascorbic acid is necessary for
hydroxylation of Tryptophan to 5-hydroxy
tryptophan. This is required for the
formation of serotonin.
4. TYROSINE METABOLISM:
5. IRON METABOLISM:
6. HAEMOGLOBIN METABOLISM:

111. 7.FOLIC ACID METABOLISM
8.STEROID SYNTHESIS
9.PHAGOCYTOSIS
10. ANTI-OXIDANT PROPERTY
11. CATARACT

112. • DEFICIENCY MANIFESTATIONS OF VITAMIN C
1. Scurvy
2. Infantile scurvy( Barlow’s disease)
3. Haemorrhagic tendency
• abnormal collagen
• Petechiae
• Ecchymoses

113. 4. Internal Haemorrhage:
• Oral cavity- painful, swollen,spongy gums
• Bones- Fractures easily, swelling of joints
• Anemia- Microcytic, hypo chromic anemia
Poikilocytosis and anisocytosis
1. Loss of blood
2. Decreased iron absorption
3. Decreased THF4
4. accumulation of meth Hb

114. • Dietary source:
1. Amla, guava,lime,lemon,green leafy
vegetables
2.Requirement( RDA ):
75 mg per day in normal adults
100 mg per day in pregnancy, lactation,and aged
people.
3. Therapeutic use:
Adjuvant in infections
In the treatment of ulcer-trauma burns