Dr. Ifat Ara Begum
Assistant Professor (Biochemistry)
Dhaka Medical College, Dhaka
Organic nutrients required in small quantities
for different biological functions &
maintenance of normal metabolic integrity
and which generally can not be synthesized
in the body or can’t be synthesized enough to
meet the body needs , so must be supplied in
Vitamin D, K, B12, Niacin (B3) & Biotin can
be synthesized in body.
CRITERIA OF WATER
Hydrophilic & soluble in aqueous media
Retain shorter period of time in the body except
vitamin B12 /folic acid which is stored in the liver
No carrier protein (LP/specific protein) is needed
Are lost rapidly by urinary excretion
Active absorption of vitamin B1/B2/ folic acid &
vitamin C from intestinal tract. Rest are absorbed
through intestinal mucosa by passive diffusion.
Absorption is not dependent on fat absorption.
Precursors of coenzyme for enzymes of
Susceptible to heat
Deficiency s/s occurs relatively quickly on an
inadequate diet, correction/cure of s/s occurs
rapidly as well on administration
Regular dietary supplementation is required
NAME OF WATER SOLUBLE
1. Vitamin B Complex:
-Pantothenic acid (B5)
-Folic Acid (B9)
2. Vitamin C (Ascorbic acid)/ Non-B complex
VITAMIN B ACTS AS CO-ENZYMES
Vit B as coenzymes:
VITAMIN B COMPLEX
• These vitamins are chemically not related
to one another. They are grouped together,
because, all of them function in the cells
Serves as a coenzyme for PDH (that catalyzes
breakdown of Pyruvate to Acetyl CoA & CO2) ,
α-KGDH (oxidative decarboxylation of α-KG to
Succinyl CoA & CO2) and transketolase (in
HMP shunt pathway of glucose)
Helps to maintain nerve conduction and
functioning of nervous system.
Beriberi: Early symptoms of beriberi are
anorexia & weakness. It may be wet beriberi /
dry beriberi / cerebral beriberi ( Wernicke-
Dry beriberi : CNS manifestations are major
features. Peripheral neuritis with sensory
disturbances leads to complete paralysis.
Wet beriberi: Cardiovascular manifestations are
prominent. Edema of leg, face & serous cavities
are the main features. Death occurs due to heart
Wernicke- Korsakoff syndrome /Cerebral
beriberi: Clinical features are those of
encephalopathy (occurring in acute thiamine
deficiency & affects CNS) plus psychosis
(occurring in chronic thiamine deficiency &
affects CNS) . It is seen only when the nutrition
is severely affected, either due to dietary
insufficiency or due to impaired absorption of
Polyneuritis: Common in chronic alcoholics.
Things to remember:
Oxidative decarboxylation of pyruvate and α-
KG have key role in energy metabolism. In
thiamine deficiency, ATP production is decreased
with impaired cellular functions.
Glucose is the only fuel for neurons & as
optimum thiamine is specifically important for
glucose oxidation, so deficiency of thiamine
will affect the activity of nervous system.
Impaired oxidation of pyruvate to acetyl CoA
forces the pyruvate to be converted to lactate.
Lactate acts as vasodilator leading to increased
venous return, high output heart failure and
Thiamine is useful in the treatment of beriberi,
alcoholic polyneuritis, neuritis of pregnancy &
neuritis of old age.
VITAMIN B2 / RIBOFLAVIN
Active form (Coenzyme form):
FMN (Flavin + Ribitol + Phosphate), FAD
(FMN + AMP)
RDA: 1.5- 2 mg
Dietary Source: Same as thiamine.
Rich sources are liver, dried yeast, egg & whole
milk. Good sources are fish, whole cereals,
legumes & green leafy vegetables
Coenzyme in 0xidation & reduction reaction
Concerned with energy metabolism as
prosthetic group of flavoproteins: Enzymes
containing riboflavin are called flavoproteins.
The 2 coenzymes are FMN & FAD. The enzyme
complex contains molybdenum and iron also.
During oxidation, FAD accepts 2 hydrogen
atoms from substrate. In turn, FAD is reduced to
FADH2 when oxidized in ETC, will
generate ATP molecules.
FAD dependent enzymes: Succinate DH,
PDH, Xanthine oxidase, α-KGDH , Acyl
Endogenous source: Produced from
amino acid, tryptophan. 1 mg niacin
(nicotinic acid) is produced from 60 mg
Exogenous source: plant & animal source
RDA: 16-20 mg (Tryptophan provides
only 10% of RDA)
Coenzyme in 0xidation & reduction
Functional part of NAD & NADP
Role in energy metabolism.
NAD dependent enzymes: PDH, LDH
Reduction of plasma LDL-C and raises plasma
HDL-C (treatment of type IIb
hyperlipoproteinemia, which is featured by
raised VLDL& LDL)
At a dose of 1.5 gm/D, niacin inhibits lipolysis
in adipose tissues & reduces plasma FFA.
Decreased plasma FA concentration causes
reduced FA influx into hepatocytes leading to
decreased production of VLDL & LDL
Dermatitis: Bright red erythema esp. in feet,
ankles & face. Increased pigmentation around
the neck is know as Casal’s necklace.
Diarrhoea: Mild to severe with blood &
mucous. Nausea & vomiting may also present.
Dementia: Seen frequently in chronic cases.
Delirium is common in acute pellagra.
Irritability, inability to concentrate & poor
memory are more common in mild cases.
VITAMIN B5 / PANTOTHENIC
Active form (Coenzyme form):
Coenzyme A (CoA-SH) & Acyl carrier
RDA: 5-10 mg
Dietary Sources: Same as thiamine. Yeast, liver
& eggs are good sources.
Formation of active acetate (acetyl CoA),
which is used as raw material for synthesis of
FA, cholesterol, ketone bodies, Ach etc & can be
oxidized in TCA cycle as common end product
of CHO, protein & fat catabolism.
Formation of active succinate (succinyl CoA),
which is used for synthesis of heme and
CoA-SH helps in FA oxidation & ACP helps in
Coenzyme for transamination & deamination
(during amino acid metabolism) & glycogen
phosphorylase (during glycogenolysis)
Helps in all decarboxylation reaction of AAs
(like decarboxylation of histidine and glutamate
to produce histamine & GABA respectively)
Porphyrin & heme synthesis
Synthesis of catecholamine & serotonin
Neurological: PLP dependent enzymes function
poorly. So, serotonin, epinephrine, noradrenalin
& GABA are not produced properly and
therefore, neurological symptoms are quite
In children: Convulsion due to decreased
formation of GABA
PLP is involved in synthesis of sphingolipids, so,
B6 deficiency leads to demyelination of nerves &
consequent peripheral neuritis.
Dermatological: Deficiency of vitamin B6
affects tryptophan metabolism. Since niacin is
produced from tryptophan, there will be
development of niacin deficiency (Pellagra)
Hematological: Hypochromic microcytic
anemia occurs due to inhibition of heme
synthesis. Impaired antibody production is
reported as well.
Disorders of AA metabolism
Causes of B6 deficiency:
i. Treatment of TB with INH (Common cause)
ii. Rare causes: Newborn infant fed with infant
formula, women taking OCP, Alcoholics.
Link of INH with B6 deficiency: INH forms an
inactive derivative with Pyridoxal phosphate. So
it is recommended to prescribe B6 rich diet during
treatment with INH
VITAMIN B7 / BIOTIN
Biotin has one carboxyl group which links with a
lysine residue in the apo-enzyme. It is also
known as vitamin H or coenzyme R.
Active form (Coenzyme form):
Covalently bound prosthetic group of
carboxylase enzyme. It is active as biotin.
RDA: 200 microgram
Endogenous source: Produced by gut flora
which is almost sufficient to meet the body need.
Exogenous source: plant & animal source like
Coenzyme for carboxylation reactions / cofactor
responsible for CO2 transfer in several
carboxylase enzymes, like Acetyl CoA
carboxylase alpha, Acetyl-CoA carboxylase beta,
Propionyl-CoA carboxylase, Pyruvate
carboxylase, etc. Biotin is important in fatty acid
synthesis, branched-chain amino acid
catabolism, and gluconeogenesis.
Biotin antagonists: Avidin, a protein present in
egg white, has great affinity to biotin. So,
addition of raw egg white in diet may cause
biotin deficiency. Avidin tightly binds with
biotin hampering absorption of biotin.
Impaired fat & carbohydrate metabolism
VITAMIN B9 / FOLIC ACID /
The terms “Folic acid” and “Folate” are often
used interchangeably. Folic acid, the more stable
form, occurs rarely in foods or the human body
but is the form most often used in vitamin
supplements and fortified foods. Naturally
occurring folates exist in many chemical forms.
Folates are found in foods as well as in
metabolically active forms in the human body.
VITAMIN B9 / FOLIC ACID
It is composed of 3 constituents. The pteridine
group linked with PABA is called pteroic acid. It
is then attached to glutamic acid to form
pteroylglutamic acid or folic acid.
Metabolism of folic acid:
Natural folic acid (usually in polyglutamate
form) cleaves in intestinal lumen to
monoglutamyl folate & absorbed. But dietary
folic acid is absorbed as such followed by its
deglutamination to monoglutamyl folate in
intestinal cell, from which it goes to blood.
Absorbed folic acid is then activated to FH4
(tetrahydrofolate) via FH2 (dihydrofolate)
through 2 steps reduction process in liver. Folic
acid is stored in liver to some extent . Total body
store is 12-15 mg, that can support body demand
for 4-6 months after stoppage of folic acid
Carrier of 1-C units of different AAs to use them
for synthesis of purines, pyrimidines, DNA,
RNA, methionine, choline etc. [Common 1-C
units are methyl (CH3) / methylene (CH2) /
methenyl (CH) / formyl (CH=O) group]
Helps in neural tube development in early fetal
Causes of folate deficiency:
Increased demand but lack of intake /
absorption as seen in dietary deficiency,
pregnancy, drugs (like anticonvulsant drugs,
etc), hemolytic anemia
Megaloblastic anemia: Reduced DNA
synthesis is the cause. In folic acid deficiency,
thymidylate synthase enzyme is inhibited , so
dTTP is not available for DNA synthesis. Very
rapidly dividing cells in bone marrow &
intestinal mucosa are therefore most seriously
Due to failure of rapid DNA synthesis, large
proerythroblasts can’t divide rapidly to make
small sized mature RBC, rather premature
relatively large blast cells appear in circulation
leading to megaloblastic anemia
NTDs in fetus during pregnancy like spina
bifida, anencephaly etc
Sulfonamides: They have structural similarity
with PABA. Bacteria synthesizes folic acid from
pteridine, PABA & glutamate. When
sulfonamides are given , microorganisms can’t
synthesize folic acid & hence their growth is
inhibited. Thus sulfonamides are very good
antibacterial agents, which do not affect the
Aminopterin & Amethopterin (methotrexate):
These are powerful inhibitors of folate reductase
& THFA generation. Thus these drugs decrease
the DNA formation & cell division. They are
widely used as anti-cancer drugs.
VITAMIN B12 / COBALAMIN
/EXTRINSIC FACTOR OF CASTLE /
ANTIPERNICIOUS ANEMIA FACTOR
Chemistry: It contains one cobalt atom. Four
pyrrole rings coordinated with a cobalt atom is
called a Corrin ring. The 5th valency of the cobalt
is linked to a benzimidazole ring. This is then
called cobalamin. The 6th valency of cobalt is
satisfied by any of the following groups:
cyanide, hydroxyl, adenosyl or methyl.
Cyanocobalamin: Cobalamin + Cyanide. This
is the commercial form.
Methyl cobalamin: Cobalamin + Methyl group.
It is the main circulating form.
5’-deoxy adenosyl cobalamin: Cobalamin + 5’-
deoxyadenosine. It is the main storage form.
Hydroxy cobalamin: Cobalamin + Hydroxyl
group. Injectable preparations are in this form.
Endogenous source: Produced by gut flora
Exogenous source: only animal source. Liver is
the richest source.
Absorption of vitamin B12:
Dietary vitamin B12 in intestine complexes with
IF (a glycoprotein secreted by parietal cell of
gastric mucosa , which is essential for absorption
of vitamin B12)
The complex travels through gut & eventually
binds to its specific receptor in ileal mucosa
Transport of bound cobalamin from ileum into
the mucosal cells, where the complex is cleaved
to yield free B12 that is subsequently absorbed
In blood B12 is transported with a protein called
Absorbed B12 is stored in liver , which is not
depleted until 5-6 years after cessation of intake
Interconversion of homocysteine & methionine to
maintain methionine store & ensure availability of
FH4 to participate in purine, pyrimidine & NA
Conversion of propionyl CoA to succinyl CoA
(during metabolism of odd chain FA) and this succinyl
CoA enters into TCA cycle later.
Maintains myelin sheath & epithelial cells
Helps in hemopoiesis by ensuring availability of FH4
(FH$ is needed for DNA synthesis & rapid DNA
synthesis is necessary for hemopoiesis).
Megaloblastic anemia: Happens due to 2ndary
deficit of FH4 as a result of accumulation of folic
acid as non-functional methyl-FH4 (folate trap).
In FH4 deficiency, there is failure of rapid DNA
synthesis, so proerythroblasts can’t divide
rapidly to make small sized mature RBC and
hence premature relatively large blast cells
appear in circulation leading to megaloblastic
Neurological disorders: Due to progressive
demyelination. e.g. Sub acute combined
degeneration of spinal cord, peripheral
neuropathy, dementia, optic atrophy
Hyperhomocysteinemia & atherosclerosis:
Homocysteine level in blood is related with MI.
Both B12 & folic acid participate in purine,
pyrimidine & NA synthesis. Folic acid in its
active form, FH4 participates directly as a carrier
of 1-C unit from AAs, whereas, B12 in its active
form (methyl cobalamin) acts indirectly by
ensuring the conversion of methyl FH4 back to
FH4, so that FH4 can again carry 1-C units to
participate again in the synthesis of purine,
pyrimidine & NA.
In B12 deficiency, methyl FH4 can’t be converted
back to FH4. So, available folate is trapped in the
form of non-functional methyl-FH4. This is
called folate trap. It leads to impairment of the
synthesis of purine, pyrimidine & NA with
consequent megaloblastic anemia.
A form of megaloblastic anemia that occurs in
vitamin B12 deficiency following failure of gastric
parietal cells to secret IF, which is necessary for
vitamin B12 absorption.
Lack of IF for absorption of vitamin B12 is more
common than dietary deficiency.
IF deficiency is usually caused by autoimmune
disease of gastric parietal cells or by generation
of anti-IF antibodies. It may be due to total /
partial gastrectomy even.
Vitamin B12 deficiency blocks the metabolism of
folic acid via folate trap metabolism, leading to
functional / secondary folic acid deficiency. As
FH4 is needed for DNA synthesis, there occurs
impaired erythropoiesis & large proerythroblasts
fails to divide rapidly to make mature RBC and
blast cells appear in blood.
Severe vitamin B12 deficiency following IF
deficiency cause severe form of megaloblastic
anemia, hence the name is pernicious anemia.
Megaloblastic anemia vs Pernicious anemia:
Megaloblastic anemia refers to any condition
which causes large red blood cells (folate
deficiency, Vitamin B12 deficiency, etc.)
Pernicious anemia can be thought of as a *type*
of megaloblastic anemia which is caused by
Vitamin B12 deficiency secondary to
malabsorption of vitamin B12 due to deficiency of
VITAMIN C / L-ASCORBIC
ACID / ASCORBATE
Water soluble and easily destroyed by heat,
alkali & storage.
In process of cooking, 70% of vitamin C is lost.
Structural formula closely resembles that of
A reducing agent & the strong reducing property
depends on the double bonded carbons
Readily oxidized by oxygen.
Ascorbate means anion form of ascorbic acid.
Readily excreted in urine.
Since vitamin C is a strong reducing agent, the
Benedict’s test will be positive in the urine
sample after the vitamin administration.
Active form: Ascorbic acid / Ascorbate
RDA: 60-80 mg
Dietary sources: Citrus fruits (lemon, orange,
amoloki, guava, tomato, etc) , green chili &
green leafy vegetables.
Post-translational maturation of collagen:
Done by vitamin C dependent hydroxylation of
proline & lysine residues of collagen following
their synthesis. Hydroxyproline & hydroxylysine
are essential for the formation of cross-linking in
collagen, which gives the tensile strength of the
Enhances absorption of iron: By reducing
dietary iron (which is mostly in ferric form and
cant be absorbed in such) in to readily
absorbable ferrous form.
Reduces serum cholesterol concentration : By
synthesis of bile acids and bile salts from
cholesterol in liver and thus facilitating
cholesterol excretion in the form of bile salts
through fecal routes.
Acts as anti-oxidant: Therefore, diet rich in
vitamin C may reduce risk of coronary heart
disease & certain cancers but clinical trials about
these claims are not yet very much convincing.
Helps in catecholamine synthesis
Participates in steroid hormone synthesis
Therapeutic use of vitamin C: Recommended
for treatment of ulcer, trauma & burns.
“Scurvy” which is characterized by swollen,
spongy and bleeding gums with loosened teeth,
fragile blood vessels, bleeding under the skin
and in deep tissues (cutaneous bleeding leading
to woody leg due to capillary hemorrhage,
spontaneous bruising, joint hemorrhage,
epistaxis, hemorrhage in GIT, etc) , soreness and
stiffness of the joints and lower extremities,
swollen joints, slow wound healing, and anemia
(iron deficiency anemia).