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Water-soluble Vitamins
R. C. Gupta
Professor and Head
Dept. of Biochemistry
National Institute of Medical Sciences
Jaipur,...
Vitamins:
A heterogeneous group of
organic compounds
Essential for animals and
human beings
Required in very minute
quanti...
Vitamins do not provide energy
But their dietary intake is essential
They perform some functions vital for
normal health, ...
Deficiencies of vitamins produce specific
diseases
These can be cured by taking the deficient
vitamins or foods containing...
Several deficiency diseases were
discovered long before the discovery of
the vitamins
In some instances, the treatment was...
Scurvy was common in sailors going on
long voyages
It was debilitating and even fatal
EMB-RCG
A poster on scurvy
James Lind cured scurvy by giving lemons
Vitamin C was discovered much later
Beriberi was common in people whose
staple diet consisted of polished rice
It was cured by giving them rice
polishings; th...
The chemical natures of vitamins were not
known at the time of their discovery
Hence, they were named after the letters
of...
Vitamins can be classified into
two groups on the basis of their
solubility:
Water-soluble vitamins
Fat-soluble vitamins
E...
Water-soluble vitamins
Soluble in water
Not stored in the body
Excess intake is wasteful
Excess intake doesn’t cause toxic...
Water-soluble vitamins
include:
Vitamin B-complex family
Vitamin C
EMB-RCG
B-complex family comprises:
Thiamin
Riboflavin
Niacin
Pantothenic acid
Pyridoxine
Biotin
Folic acid
Cobalamin
EMB-RCG
As water-soluble vitamins are not stored
in the body, they must be taken every day
Losses can occur during cooking as some...
Some water-soluble vitamins can be
synthesized by intestinal bacteria
If intestinal bacteria are destroyed, e.g. by
antibi...
Thiamin (vitamin B1) is heat-stable in acidic
medium but not in basic medium
It is oxidized by mild oxidizing agents to
th...
Thiamin forms a coenzyme, thiamin
pyrophosphate (TPP)
It is also known as thiamin diphosphate
(TDP)
Functions
Thiamin pyrophosphate
C
C
C CH
CC
CH
‒ CH2 ‒ CH2 ‒ O ‒ P ‒ O ‒ P ‒OH
S
N
N
NH2
Ι
‒ CH2 ‒ N+
ΙΙ ΙΙ
ΙΙ
O O
OHOH
Ι
CH3
H3C‒
TPP is a coenzyme for:
1. Transketolase
2. a-Keto acid dehydrogenases
Transketolase is a coenzyme in the
hexose monophosphate shunt
a-Keto acid dehydrogenases include:
• Pyruvate dehydrogenase...
Activity of a-keto acid dehydrogenases
is impaired in thiamin deficiency
This can limit the availability of energy
Sources of
thiamin
Yeast
Kidney
FishMeat
Pulses
Liver
Cereals Nuts
In cereals, thiamin is present mainly in the
outer layer of the grain
Removal of the outer layer, e.g. by milling,
causes ...
The recommended daily allowance (RDA)
for thiamin is 0.5 mg/1,000 kcal of energy
or 1-1.5 mg/day in adults
The requirement...
People consuming polished rice or refined
wheat flour are prone to thiamin deficiency
Outer layer of the grain is removed ...
Refined white flour has much less
thiamin than whole wheat flour
Refined white flour Whole wheat flour
Parboiling of rice decreases the loss of
thiamin
Polished rice Parboiled rice
During parboiling, paddy is soaked in warm
water for a few hours and is, then, steam-
dried
Thiamin percolates into the de...
Alcoholics are prone to thiamin deficiency
as alcohol impairs:
• Absorption of thiamin
• Conversion of thiamin into TPP
Deficiency of thiamin
causes beriberi which
affects:
Central nervous system
Cardiovascular system
Gastrointestinal tract
E...
Thiamin deficiency causes peripheral
neuritis involving sensory and motor nerves
Sensory involvement leads to hyper-
aesth...
The heart muscle becomes weak resulting
in congestive heart failure
This, in turn, causes oedema and ascites
Cardiovascula...
Involvement of gastrointestinal tract
causes:
• Anorexia
• Dyspepsia
• Constipation
Gastrointestinal tract
Oedema is a common feature if cardio-
vascular system is involved
Hence, beriberi mainly involving cardio-
vascular system...
Involvement of central nervous system
doesn’t cause oedema
Hence, beriberi mainly involving central
nervous system is know...
Infantile beriberi can occur when mother is
deficient in thiamin
It usually occurs between two and six
months of age
It is...
Vomiting, diarrhoea, hoarseness and
weight loss are common in infantile beriberi
The disease responds promptly to thiamin
...
Laboratory findings in beriberi are:
• Increased pyruvic acid level in blood
• Decreased thiamin concentration in RBCs
• D...
Riboflavin was known in the past as
vitamin B2
It is heat-stable in neutral and acidic
medium but not in basic medium
Its ...
Chemically, riboflavin is 6,7-dimethyl-9-D-
ribityl isoalloxazine
Riboflavin can be readily reduced to
leucoriboflavin
Riboflavin (6,7-dimethyl-9-D-ribityl isoalloxazine)
H C—3
||
1
2
45
6
7
8 9
10
CH —C—C—C—CH OH2 2
H
|
OH
|
OH
|
OH
|
H
|
H...
Functions
Riboflavin functions in the
form of two coenzymes:
Flavin
mononucleotide
(FMN)
Flavin adenine
dinucleotide
(FAD)
FMN and FAD can undergo reversible
oxidation and reduction
They participate in a number of oxidation-
reduction reactions ...
H C—3
||
CH — C — C — C — CH — O — P — OH2 2
H
|
OH
|
OH
|
OH
|
H
|
H
|
NN
N
H C—3 O
NH
O
||
|
OH
H C —3
||
H
NN
N
H
H C —...
FMN is a:
Constituent of respiratory
chain
Constituent of microsomal
hydroxylase system
Coenzyme for L-amino
acid oxidase
...
HC—3
||
NN
N
HC—3 O
NH
FAD
HC—3
||
N
HC—3 O
NH
H
N
N
H
AH 2
A
N
N
N
N
NH 2
NH 2
H
|
OH
|
OH
|
OH
|
OH
|
H
|
H
|
O
||
CH— C...
FAD is a:
Constituent of respiratory
chain
Constituent of microsomal
hydroxylase system
Coenzyme for many
enzymes
EMB-RCG
Some enzymes requiring FAD as a
coenzyme are:
• D-Amino acid oxidase
• Acyl CoA dehydrogenase
• Succinate dehydrogenase
• ...
Dietary
sources of
riboflavin
Milk Dairy products Eggs
Meat Nuts Leafy vegetables
Kidney Liver
The recommended daily allowance (RDA)
for riboflavin is 0.6 mg/1,000 kcal
Or it is 2 mg/day for adults
Requirement
An isolated deficiency of riboflavin is rare
It is generally combined with other
deficiencies
Deficiency
Angular stomatitis
(fissures at the angles of mouth)
Cheilosis (cracked and swollen lips)
Glossitis
(swollen, painful, mag...
Angular stomatitis and glossitis
Laboratory diagnosis of riboflavin deficiency
is difficult
Serum and urinary riboflavin are low in
severe deficiency
Eryth...
Niacin was known in the past as anti-
pellagra factor, pellagra-preventing factor
and vitamin B3
It occurs in two forms, n...
Niacin and niacinamide are equally active
Niacin is converted into niacinamide in the
body
Niacin
(nicotinic acid)
Niacinamide
(nicotinamide)
N N
–COOH –CONH2
Functions
Niacin performs its functions in the
form of two coenzymes:
Nicotinamide
adenine dinucleotide
(NAD)
Nicotinamide...
Nicotinamide combines with ribose and
phosphoric acid to form a nucleotide
This combines with an adenine nucleotide
to for...
— CONH2
CH — O — P — O — P — O — CH2 2
NN
+
N
NH2
|
N
OH*OH
HH
OHOH
HH
H H HH
OO
N
OH
|
OH
|
O O
|| ||
NAD (in NADP, —OH* ...
— CONH2
CH — O — P — O — P — O — CH2 2
NN
+
N
NH2
|
N
OH*OH
HH
OHOH
HH
H H HH
OO
N
OH
|
OH
|
O O
|| ||
NAD (in NADP, —OH* ...
NAD and NADP can undergo reversible
oxidation and reduction
They can act as coenzymes for several
oxido-reductases
CH CHC ...
NAD and NADP act as coenzymes in
many metabolic pathways such as:
• Glycolysis
• Hexose monophosphate shunt
• Citric acid ...
NAD generally acts as coenzyme in
catabolic pathways
NADP generally acts as coenzyme in
anabolic pathways
Some enzymes which require NAD as a
coenzyme are:
• Lactate dehydrogenase
• Pyruvate dehydrogenase
• Isocitrate dehydrogen...
NAD is also a
constituent of:
Respiratory
chain
Microsomal
hydroxylase
system
Examples of enzymes requiring NADP
as a coenzyme are:
• Glucose-6-phosphate dehydrogenase
• 6-Phosphogluconate dehydrogena...
Sources of niacin
Eggs
Fish Tomatoes
Green leafy
vegetables
Milk Meat
Niacin is also synthesized in human beings
from tryptophan
It has been shown that 1 mg of niacin is
synthesized from 60 mg...
Pyridoxal phosphate is required as a
coenzyme for synthesis of niacin
Excess of leucine inhibits the conversion
of tryptop...
The daily requirement for niacin is 6.6
mg/1,000 kcal
Or the adult requirement can be taken as
20 mg/day
Requirement
Deficiency of niacin causes pellagra
Clinical features are stomatitis, glossitis,
diarrhoea, dermatitis and dementia
If un...
Dermatitis usually affects the exposed
parts of the body
Dermatitis in pellagra
Pellagra is common in people consuming
maize and sorghum as their staple food
These two are poor in niacin and
tryptophan,...
Pantothenic acid was known in the past as
vitamin B5
It is heat-stable in neutral medium but not
in acidic or basic medium...
Pantoic acid
Pantothenic acid
b-Alanine
Pantothenic acid is made up of
pantoic acid and b-alanine
Functions
• Coenzyme A
(CoA)
• Acyl carrier
protein (ACP)
Pantothenic acid
performs its
functions as a
constituent of:
Bot...
Pantothenic acid is first phosphorylated at
C4 of the pantoic acid residue
The product is 4’-phosphopantothenic acid
This ...
CH — C — CH — C — N — CH — CH —2 2 2 C — N — CH — CH — SH2
CH3
|
H
|
H
|
COOH
|
O
||
O
||
CH3
| ||
OHO
|
O = P — OH
4´-Pho...
Decarboxylation of the cysteine residue
converts 4’-phosphopantothenyl cysteine
into 4’-phosphopantetheine
4’-Phosphopante...
N
N
NH2
|
N
OH
H
O
H
H
N
O = P — OH
H
|
|
CH2
|
O = P — OH
CH C CH C N CH CH2 2 2— — — — — — — C — N — CH — CH — SH2 2
CH3...
In ACP, 4’-phosphopantetheine is esterified
with a serine residue of the protein
The –SH group of 4’-phosphopantetheine
re...
Coenzyme A is also represented as CoA-
SH as its terminal –SH group binds various
compounds
Coenzyme A participates in a v...
Examples of reactions requiring
coenzyme A are:
• Oxidative decarboxylation of a-keto
acids
• Activation of fatty acids
• ...
A number of coenzymes are required in
this multi-step reaction
Coenzyme A is one of them
Oxidative decarboxylation of
a-ke...
R ‒ C ‒ COOH + CoA‒SH + NAD+
O
‖
R ‒ C ~ S‒CoA + NADH + H+ + CO2
O
‖
a-Keto acid
Acyl CoA
Oxidative decarboxylation
Pyruvate is converted into acetyl CoA by
oxidative decarboxylation
a-Ketoglutarate is converted into succinyl
CoA by oxida...
Before fatty acids can take part in any
reaction, they have to be converted into
their CoA derivatives
This reaction, know...
R ‒ CH2 ‒ COOH + CoA‒SH + ATP
R ‒ CH2 ‒ C ~ S‒CoA + AMP + PPi
O
‖
Fatty acid
Acyl CoA
Activation of fatty acid
Some amino acids are converted into their
CoA derivatives before they can be
metabolized
Examples are leucine, isoleucine ...
An important role of CoA is to provide
active acetate (acetyl CoA)
Active acetate is required for synthesis of
fatty acids...
Coenzyme A also forms active succinate
(succinyl CoA)
Active succinate is required for haem
synthesis and for gluconeogene...
Pantothenic acid is a constituent of acyl
carrier protein (ACP) also
ACP is a part of the multienzyme complex
which cataly...
Pantothenic acid is widely distributed in
animal and plant foods
It is also synthesized by intestinal bacteria
Sources
Dietary sources of
pantothenic acid
LiverKidney Meat
Eggs
Wheat Peas
Sweet
potatoes
Yeast
The recommended daily intake is 10 mg
A smaller intake may be sufficient for
infants and children
Requirement
Deficiency of pantothenic acid has not
been reported in human beings
In animals, deficiency causes loss of
weight, loss of...
Human deficiency can be produced
experimentally
It leads to neurological and gastrointestinal
disturbances
Pyridoxine was known in the past as
vitamin B6
It consists of three closely related pyridine
derivatives
These are pyridox...
CH OH
|
2 CHO
|
CH NH2 2
|
—CH OH2 —CH OH2 —CH OH2HO— HO— HO—
H C—3 H C—3 H C—3
N N N
Pyridoxine Pyridoxal Pyridoxamine
N ...
Pyridoxine, pyridoxal and pyridoxamine
are converted into coenzymes
The conzymes are:
• Pyridoxine phosphate
• Pyridoxal p...
Pyridoxine, pyridoxal and pyridoxamine are
phosphorylated by a common enzyme
The three coenzymes are interconvertible
The ...
N
HO‒
H3C‒
‒CH2OH
CH2OH
Ι
CH2OH
Ι
HO‒
H3C‒
‒CH2‒O‒P‒OH
+ ATP + ADP
‖
O
OH
Pyridoxine Pyridoxine phosphate
Pyridoxal
kinase...
N
HO‒
H3C‒
‒CH2OH
CHO
I
CHO
I
HO‒
H3C‒
‒CH2‒O‒P‒OH
+ ATP + ADP
‖
O
OH
Pyridoxal Pyridoxal phosphate
Pyridoxal
kinase
N
I
N
HO‒
H3C‒
‒CH2OH
CH2NH2
I
CH2NH2
I
HO‒
H3C‒
‒CH2‒O‒P‒OH
+ ATP + ADP
‖
O
OH
Pyridoxamine Pyridoxamine phosphate
Pyridoxal
...
Vitamin B6 coenzymes are required mainly
in the metabolism of amino acids
Pyridoxal phosphate (PLP) can form a
Schiff base...
Schiff base
The amino acid, thus bound, can undergo
various reactions
Ι
‖
Ι
H3C‒
HO‒ ‒CH2‒O‒ P
C‒H
R‒CH‒COOH
N
N
The amino acid bound to pyridoxal
phosphate can undergo:
• Transamination
• Deamination
• Decarboxylation
• Transulphurati...
Pyridoxal phosphate is also required
in:
• Metabolism of tryptophan
• Synthesis of haem
• Cellular uptake of amino acids
•...
These reactions are catalysed by specific
transaminases
The amino group of an amino acid is
transferred to an a-keto acid
...
Transamination reactions are important
in:
• Formation of new amino acids
• Catabolism of amino acids
 Subjects deficient in thiamin retain most of the
test dose in tissues and excrete less in urine
 Measurement of transke...
Deamination
PLP acts as a coenzyme for:
• Serine deaminase
• Threonine deaminase
Decarboxylation
PLP is a coenzyme for
decarboxylases acting on:
• Glutamate
• Arginine
• Tyrosine
PLP is a coenzyme for cystathionine
synthetase and cystathionine g-lyase
These two transfer sulphur from
homocysteine to s...
PLP is a coenzyme for cysteine
desulphydrase
This enzyme removes the sulphydryl group
from cysteine
Desulphydration
One of the intermediates in the catabolism
of tryptophan is 3-hydroxykynurenine
This is converted into 3-hydroxyanthranili...
When PLP is not available, 3-hydroxy-
anthranilic acid is not formed
3-Hydroxykynurenine is spontaneously
converted into x...
Tryptophan 3-Hydroxy-
kynurenine
Kynureninase
3-Hydroxy-
anthranilic acid
Excreted in
urineAcetoacetyl CoA
Xanthurenic
aci...
One of the enzymes involved in the
synthesis of haem is d-aminolevulinic acid
synthetase
This enzyme requires PLP as a coe...
Cellular uptake of L-amino acids is an
active process
This requires the participation of pyridoxal
phosphate
Cellular upta...
Gamma-amino butyric acid (GABA) acts as
a neurotransmitter in brain
It is formed by the action of glutamate
decarboxylase ...
Phosphorylase is a key enzyme of glyco-
genolysis
Phosphorylase requires PLP as a
coenzyme
Glycogenolysis
Sources of pyridoxine include animal as
well as plant foods
Another source is bacterial synthesis in
the intestine
Sources
Dietary
sources of
pyridoxine
Leafy
vegetables
Meat
Eggs
Milk
Wheat
Corn Beans
Potato
Bananas
Pyridoxine is mainly required in the
metabolism of amino acids
Its requirement depends upon the protein
intake
An intake o...
Deficiency is very rare
It may sometimes occur in infants and
pregnant women
Deficiency may also occur in patients
taking ...
Clinical features of pyridoxine deficiency
are:
• Nausea
• Vomiting
• Dermatitis
• Microcytic anaemia
• Convulsions
Convul...
Chronic pyridoxine deficiency may cause
hyperhomocysteinaemia
Hyperhomocysteinaemia increases the
risk of cardio-vascular ...
Urinary excretion of xanthurenic acid is
increased in pyridoxine deficiency
Measuring xanthurenic acid excretion
Giving a ...
Biotin is also known as anti-egg white
injury factor
When raw egg white is fed to rats, they
develop some symptoms which a...
It has been shown that raw egg white
contains a protein, avidin
Avidin forms a complex with biotin
preventing its intestin...
Avidin is inactivated by heat
Therefore, cooked eggs do not hamper
absorption of biotin
Biotin is heat-stable
Biotin is a heterocyclic sulphur-containing
monocarboxylic acid
HN
|
HC
|
H2C
NH
|
CH
|
CH — (CH2)4— COOH
O
||
C
S
Biotin is a coenzyme for carboxylases
It is also known as co-carboxylase
Biotin is firmly bound to the enzyme
‒COOH group ...
Some carboxylation reactions
requiring biotin are:
Carboxylation of
pyruvate
Carboxylation of
acetyl CoA
Carboxylation of
...
This reaction converts pyruvate into oxalo-
acetate
Oxaloacetate is an intermediate in citric
acid cycle
This reaction is ...
CH3
|
C = O
|
COOH
+ CO2 + ATP
Pyruvate
COOH
|
CH2
|
C = O
|
COOH
+ ADP + Pi
Oxaloacetate
Pyruvate
carboxylaseBiotin
Carboxylation converts acetyl CoA into
malonyl CoA
This reaction is important in fatty acid
synthesis
Carboxylation of ace...
Carboxylation of acetyl CoA
CH3— C ~ S — CoA + CO2 + ATP
CH2— C ~ S — CoA + ADP + Pi
Acetyl CoA
Malonyl CoA
Acetyl CoA
car...
Propionyl CoA is carboxylated to D-methyl-
malonyl CoA
This is one of the reactions in the gluco-
neogenic pathway for con...
CH3
CH3
|
|
CH2
H — C — COOH
|
|
O = C ~ S — CoA + CO2 + ATP
O = C ~ S — CoA + ADP + Pi
Propionyl CoA
D-Methylmalonyl CoA
...
Bacterial synthesis in the intestine provides
sufficient amounts of biotin
Dietary sources include animal foods as
well as...
CauliflowerAvocado
Berries
Eggs Meat
Nuts Sources
of biotin
Biotin requirement is not known with
certainty as the intestinal bacteria meet
most of the requirement
The daily intake ha...
Deficiency of biotin is unknown in human
beings
Deficiency may occur in animals when
they are fed raw egg white
Deficiency
Clinical features of biotin deficiency in
animals are:
• Retarded growth
• Loss of weight
• Dermatitis
• Loss of hair
• Mu...
Folic acid is also known as folacin or
pteroylglutamic acid
It is made up of pteridine, para-amino-
benzoic acid and gluta...
H N2 N
N
|
OH
1
2
3
4
N
5
6
7
8
N
9 10
CH — N —2 — C — N — CH
| |
H COOH
COOH
|
CH2
|
CH2
|
O
||
H
|
Pteridine para-Amino-...
Folic acid is found in food as pteroyl
monoglutamate, pteroyl triglutamate and
pteroyl heptaglutamate
The last two are con...
Folic acid functions as a coenzyme,
tetrahydrofolate (H4-folate or FH4)
Folate is first reduced to 7,8-dihydrofolate
(H2-f...
Dihydrofolate
Tetrahydrofolate
Folate
Dihydrofolate reductase
Dihydrofolate reductase
NADPH + H+
NADPH + H+
NADP+
NADP+
Amethopterin and aminopterin are
competitive inhibitors of dihydrofolate
reductase
They act as folic acid antagonists or f...
H4-Folate is a carrier of one-carbon units
The one-carbon unit may be attached to N5
or N10 of H4-folate
The one-carbon units carried by H4-
folate may be:
• Formyl (–CHO) group
• Formate (–HCOO‒) group
• Methyl (–CH3) group
• ...
H N2 N
N
N
H
5
H
N
10
CH — N —2 — C — N — CH
| |
CHO COOH
COOH
|
CH2
|
CH2
|
O
||
H
|
H N2 N
N
N
|
CH3
5
H
N
10
CH — N —2 ...
H4-Folate can:
• Receive one-carbon units from
various compounds
• Transfer one-carbon units to various
compounds
Sources of one-carbon units
Tetrahydrofolate may receive
one-carbon units from:
• Formiminoglutamic acid
• Methionine
• Ch...
Formiminoglutamic acid (FIGLU) is formed
in the body from histidine:
Histidine → Urocanic acid → → FIGLU
FIGLU can transfe...
Methionine, choline and thymine are the
source of methyl groups
Serine can contribute its hydroxymethyl
group
Utilization of one-carbon units
The one-carbon unit carried by tetra-
hydrofolate can be used for synthesis of:
• Purines
...
Synthesis of purines:
The carbon atoms two and eight of
purines are contributed by f10-H4-
folate
Synthesis of serine:
The hydroxymethyl group for the
conversion of glycine into serine is
provided by N5, N10-methylene-H4...
Synthesis of methionine:
The methyl group for the conversion of
homocysteine into methionine is
provided by N5-methyl-H4-f...
Synthesis of choline:
The methyl groups for the synthesis of
choline from serine are provided by N10-
methyl-H4-folate
Synthesis of thymine:
The methyl group of thymine is provided
by N5, N10-methylene-H4-folate
Synthesis of n-formylmethionine:
• The formyl unit of f10-H4-folate converts
methionine into n-formylmethionine
• n-Formyl...
Green leafy vegetables are the major
source of folic acid
Folic acid is present in several other
vegetables, yeast, meat, ...
Sources of folic acid
Green leafy
vegetables
Other
vegetables
Fish MilkMeat
Yeast
Requirement
Infants and children 100 mg/day
Adult men and women 100 mg/day
Pregnant women 300 mg/day
Lactating women 150 m...
Folic acid is required for the synthesis of
purines and thymine
Its deficiency impairs nucleic acid synthesis
This leads t...
Megaloblasts in
folic acid
deficiency
Folic acid deficiency during pregnancy can
cause neural tube defects in the baby
This occurs very early in pregnancy
Folic...
Neural tube defect
Deficiency can be diagnosed by giving a
test dose of histidine
Urinary excretion of FIGLU is measured
after giving the tes...
Vitamin B12 exists in several forms
Cyanocobalamin was the first form
discovered
It was isolated as a red crystalline
comp...
Vitamin B12 activity was found in
compounds in which the cyanide
group is replaced by:
• Hydroxyl group (hydroxocobalamin)...
Vitamin B12 has a complex structure
Molecular formula of cyanocobalamin is
C63H88O14N14PCo
It has four pyrrole rings with ...
The cobalt atom of the corrin ring
forms co-ordination bonds with:
• Nitrogen atoms of four pyrrole rings
• Cyanide group
...
5,6-Dimethylbenzimidazole is linked with
ribose-3-phosphate
The phosphate group of ribose-3-
phosphate is linked with the ...
N
N
OH
H
O
H
H H
O
H C –3
H C –3
CH OH2
H N – OC – H C –2 2
HN – OC – H C – H C –2 2
|
CH2
|
CH – CH3
|
O
|
O = P – OH
NH2...
Vitamin B12 is heat-stable in acidic and
neutral medium
It is present in food in association with
proteins
The ingested vitamin B12 is released from
proteins by gastric hydrochloric acid
Most of the vitamin binds to R-proteins
pr...
Gastric parietal cells secrete intrinsic factor
(IF)
IF is a glycoprotein of 45 kD which can
bind vitamin B12
At low pH, a...
Most of the vitamin binds to R-proteins in
the stomach
In duodenum, R-proteins are hydrolysed
by pancreatic proteases
Vita...
One IF molecule binds one molecule of
vitamin B12
A specific receptor on ileal mucosa binds
the IF-vitamin B12 complex
The...
Most of the vitamin is bound to trans-
cobalamin II in plasma
Transcobalamin II-vitamin B12 complex is
taken up by cells w...
Transcobalamin II is hydrolysed in the cell
by lysosomal enzymes
Vitamin B12 is released, mostly in the form
of hydroxocob...
A significant amount of vitamin B12 is
stored in the body
In well-nourished adults, vitamin B12 stores
are about 2,000-5,0...
Vitamin B12 forms coenzymes known as
cobamides (B12 coenzymes)
The coenzymes are formed by replace-
ment of the cyanide or...
In methylcobalamin, the cyanide group is
replaced by a methyl group
In adenosylcobalamin, it is replaced by 5´-
deoxyadeno...
Methylcobalamin Adenosylcobalamin
The cobamides function as coenzymes,
mainly in the transfer of one-carbon units
They complement the function of tetra-
hyd...
Besides H4-folate, cobamides are also
involved in transfer of one-carbon units
An example of one such reaction is
synthesi...
H4-FolateN5-Methyl-H4-folate
MethylcobalaminCobalamin
Methionine Homocysteine
H4-Folate released in this reaction returns
...
In cobalamin deficiency, H4-folate cannot
return to folate pool
It is trapped as methyl-H4-folate (known as
folate trap)
T...
Adenosylcobalamin acts as a coenzyme
in the conversion of methylmalonyl CoA
into succinyl CoA
Methylmalonyl CoA is formed ...
CH3
|
HOOC — C — H
|
C ~ S — CoA
Methylmalonyl CoA isomeraseCobamide
L-Methylmalonyl CoA
Succinyl CoA
||
O
|
CH — C ~ S — ...
Succinyl CoA may be:
• Converted into glucose or
• Oxidized in citric acid cycle
In vitamin B12 deficiency, methylmalonic
acid is excreted in large amounts in urine
(methylmalonic aciduria)
Rarely, methy...
Vitamin B12 cannot be synthesized by any
plant or animal
It is synthesized only by some bacteria
Animals acquire it throug...
Dietary
sources of
vitamin B12
Eggs
Liver Kidney Meat
Cheese
Milk
Requirement
Age and sex Requirement
Infants and
children 0.2-1 µg/day
Adult men and
women 1 µg/day
Pregnant and
lactating ...
Deficiency
Deficiency of vitamin B12 is historically
associated with pernicious anaemia
The disease is also known as Addis...
A prescription for pernicious anaemia in 1936
Liver was believed to have an anti-
pernicious anaemia factor (APAF)
Castle (1930) showed that stomach
produced a compound...
The extrinsic factor later turned out to be
vitamin B12
The basic cause of pernicious anaemia
was found to be absence of i...
Clinical features of deficiency may take
long to develop
Hepatic stores of vitamin B12 can last
several years
The deficien...
The characteristic haematological feature is
megaloblastic anaemia
Large and immature red cell precursors are
released int...
Involvement of nervous system causes
sub-acute combined degeneration (SACD)
This is degeneration of dorsal and lateral
col...
Postrior column
Lateral column
SACD
Anterior column
Degeraration
Normal
SACD leads to sensory as well as motor
disturbances
Numbness, tingling, sore tongue and
ataxia are common neurological fea...
Deficiency of vitamin B12 is not always due
to pernicious anaemia
It can also occur due to deficient intake or
decreased a...
Ascorbic acid
Ascorbic acid (vitamin C) prevents a
specific deficiency disease, scurvy
Therefore, it is also known as anti...
Chemically, the structure of ascorbic acid
resembles that of hexoses
Like hexoses, it can exist as L- and D-
isomers
Only ...
Ascorbic acid can be readily oxidized to
dehydroascorbic acid
L-Ascorbic acid and L-dehydroascorbic
acid possess equal vit...
C = O
|
C – OH
||
C – OH
|
H – C
|
HO – C – H
|
CH OH2
H – C
C = O
|
|
|
|
HO – C – H
|
CH OH2
C = O
C = O
L-Ascorbic acid...
Vitamin C is synthesized by all plants and
animals via uronic acid pathway
Exceptions are guinea pigs and primates
which r...
From an average diet, 70 to 95% of the
ingested ascorbic acid is absorbed
However, as the intake increases, the
proportion...
Cells take up vitamin C with the help of
some transporters
The transporters involved in cellular
uptake are:
• Sodium-Vita...
SVCT1 and SVCT2 are active transport
systems for vitamin C
Transport by SVCT1 and SVCT2 is
sodium-linked
GLUT1 and GLUT3 t...
SVCT1 and SVCT2 transport the reduced
form (ascorbic acid) into the cells
GLUT1 and GLUT3 transport the oxidized
form (deh...
Tissue distribution
Total amount of ascorbic acid in an
adult is 2-3 gm
It is distributed in all tissues and body
fluids
I...
The highest concentration is found in the
adrenal glands followed by other glands
The concentration in plasma is 0.5-1.5
m...
Functions
Ascorbic acid can undergo reversible
oxidation and reduction
Hence, ascorbic acid acts as a coenzyme
in some oxi...
C = O
|
C – OH
||
C – OH
|
H – C
|
HO – C – H
|
CH OH2
H – C
C = O
|
|
|
|
HO – C – H
|
CH OH2
C = O
C = O
L-Ascorbic acid...
Ascorbic acid is required
for the synthesis of:
• Collagen
• Carnitine
• Neurotransmitters
• Tyrosine etc
Ascorbic acid acts as a coenzyme for
prolyl hydroxylase and lysyl hydroxylase
These two hydroxylate proline and lysine
res...
Hence, it is essential for the formation and
maintenance of:
• Matrix of bones
• Cartilages
• Dentine
• Blood vessels
• Sc...
Ascorbic acid is a coenzyme for e-N-
trimethyl-lysine hydroxylase and g-butyro-
betaine hydroxylase
These two are necessar...
Ascorbic acid is a coenzyme for dopamine
b-hydroxylase
This enzyme participates in the synthesis
of norepinephrine and epi...
Ascorbic acid is a coenzyme for para-
hydroxyphenylpyruvate hydroxylase
Thus, it participates in the catabolism of
tyrosine
Ascorbic acid is a coenzyme for peptidyl-
glycine a-amidating mono-oxygenase
This enzyme adds amide groups to several
pept...
Ascorbic acid is required for the formation
of bile acids from cholesterol
Cholesterol is converted into 7-a-hydroxy-
chol...
Ascorbic acid is a reductant, and keeps
iron and copper in reduced state
By converting ferric ions into ferrous ions, it
h...
Ascorbic acid also acts as an anti-oxidant
Along with other anti-oxidants, it helps in
combating oxidative stress
Sources
Indian gooseberry (amla) is the richest
source of vitamin C
All citrus fruits are rich in vitamin C
Several other ...
Sources
of
vitamin C
Green leafy
vegetables
CauliflowerTomatoes
Berries
Amla OrangeLemon
Kiwi
Considerable losses of vitamin C can
occur during cooking
Hence, some raw fruits and salads should
be included in the dail...
Requirement
Age and sex RDA (ICMR, 2010)
Infants 25 mg/day
Children and adults 40 mg/day
Pregnant women 60 mg/day
Lactatin...
Deficiency
Deficiency of vitamin C produces scurvy
A full-blown picture of scurvy is rare these
days
Isolated signs and sy...
Signs and symptoms of scurvy
include:
• Swollen, spongy and bleeding gums
• Loosening of teeth
• Petechial haemorrhages
• ...
Bleeding gums in vitamin C deficiency
Petechial haemorrhages
Laboratory diagnosis of deficiency can be
made by ascorbic acid saturation test
After a test dose of ascorbic acid, urinar...
Water soluble vitamins
Water soluble vitamins
Water soluble vitamins
Water soluble vitamins
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Water soluble vitamins

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Water-soluble vitamins for medical, biochemistry and biology students; structure, functions, sources, requirements and deficiency

Published in: Health & Medicine

Water soluble vitamins

  1. 1. Water-soluble Vitamins R. C. Gupta Professor and Head Dept. of Biochemistry National Institute of Medical Sciences Jaipur, India
  2. 2. Vitamins: A heterogeneous group of organic compounds Essential for animals and human beings Required in very minute quantities EMB-RCG
  3. 3. Vitamins do not provide energy But their dietary intake is essential They perform some functions vital for normal health, growth and reproduction EMB-RCG
  4. 4. Deficiencies of vitamins produce specific diseases These can be cured by taking the deficient vitamins or foods containing the vitamins EMB-RCG
  5. 5. Several deficiency diseases were discovered long before the discovery of the vitamins In some instances, the treatment was discovered before the discovery of the vitamin e.g. scurvy and beriberi EMB-RCG
  6. 6. Scurvy was common in sailors going on long voyages It was debilitating and even fatal EMB-RCG
  7. 7. A poster on scurvy
  8. 8. James Lind cured scurvy by giving lemons Vitamin C was discovered much later
  9. 9. Beriberi was common in people whose staple diet consisted of polished rice It was cured by giving them rice polishings; thiamin was discovered later EMB-RCG
  10. 10. The chemical natures of vitamins were not known at the time of their discovery Hence, they were named after the letters of the alphabet These names have now been largely replaced by chemical names EMB-RCG
  11. 11. Vitamins can be classified into two groups on the basis of their solubility: Water-soluble vitamins Fat-soluble vitamins EMB-RCG
  12. 12. Water-soluble vitamins Soluble in water Not stored in the body Excess intake is wasteful Excess intake doesn’t cause toxicity EMB-RCG
  13. 13. Water-soluble vitamins include: Vitamin B-complex family Vitamin C EMB-RCG
  14. 14. B-complex family comprises: Thiamin Riboflavin Niacin Pantothenic acid Pyridoxine Biotin Folic acid Cobalamin EMB-RCG
  15. 15. As water-soluble vitamins are not stored in the body, they must be taken every day Losses can occur during cooking as some of them are heat-labile EMB-RCG
  16. 16. Some water-soluble vitamins can be synthesized by intestinal bacteria If intestinal bacteria are destroyed, e.g. by antibiotic therapy, extra intake is required EMB-RCG
  17. 17. Thiamin (vitamin B1) is heat-stable in acidic medium but not in basic medium It is oxidized by mild oxidizing agents to thiochrome which is biologically inactive It is made up of a substituted pyrimidine linked by a methylene bridge to substituted thiazole Thiamin
  18. 18. Thiamin forms a coenzyme, thiamin pyrophosphate (TPP) It is also known as thiamin diphosphate (TDP) Functions
  19. 19. Thiamin pyrophosphate C C C CH CC CH ‒ CH2 ‒ CH2 ‒ O ‒ P ‒ O ‒ P ‒OH S N N NH2 Ι ‒ CH2 ‒ N+ ΙΙ ΙΙ ΙΙ O O OHOH Ι CH3 H3C‒
  20. 20. TPP is a coenzyme for: 1. Transketolase 2. a-Keto acid dehydrogenases
  21. 21. Transketolase is a coenzyme in the hexose monophosphate shunt a-Keto acid dehydrogenases include: • Pyruvate dehydrogenase • a-Ketoglutarate dehydrogenase • Branched-chain a-keto acid dehydrogenase
  22. 22. Activity of a-keto acid dehydrogenases is impaired in thiamin deficiency This can limit the availability of energy
  23. 23. Sources of thiamin Yeast Kidney FishMeat Pulses Liver Cereals Nuts
  24. 24. In cereals, thiamin is present mainly in the outer layer of the grain Removal of the outer layer, e.g. by milling, causes considerable loss of thiamin
  25. 25. The recommended daily allowance (RDA) for thiamin is 0.5 mg/1,000 kcal of energy or 1-1.5 mg/day in adults The requirement increases in alcoholics and in hyper-metabolic states e.g. fever, pregnancy, hyperthyroidism etc Requirement
  26. 26. People consuming polished rice or refined wheat flour are prone to thiamin deficiency Outer layer of the grain is removed while refining wheat flour or polishing rice Deficiency
  27. 27. Refined white flour has much less thiamin than whole wheat flour Refined white flour Whole wheat flour
  28. 28. Parboiling of rice decreases the loss of thiamin Polished rice Parboiled rice
  29. 29. During parboiling, paddy is soaked in warm water for a few hours and is, then, steam- dried Thiamin percolates into the deeper part of the grain Polishing of parboiled rice leads to a limited loss of thiamin
  30. 30. Alcoholics are prone to thiamin deficiency as alcohol impairs: • Absorption of thiamin • Conversion of thiamin into TPP
  31. 31. Deficiency of thiamin causes beriberi which affects: Central nervous system Cardiovascular system Gastrointestinal tract EMB-RCG
  32. 32. Thiamin deficiency causes peripheral neuritis involving sensory and motor nerves Sensory involvement leads to hyper- aesthesia, numbness, tingling and pain Motor involvement leads to muscular weakness, sluggish reflexes, ataxia and paralysis Central nervous system
  33. 33. The heart muscle becomes weak resulting in congestive heart failure This, in turn, causes oedema and ascites Cardiovascular system Oedema Ascites
  34. 34. Involvement of gastrointestinal tract causes: • Anorexia • Dyspepsia • Constipation Gastrointestinal tract
  35. 35. Oedema is a common feature if cardio- vascular system is involved Hence, beriberi mainly involving cardio- vascular system is known as wet beriberi
  36. 36. Involvement of central nervous system doesn’t cause oedema Hence, beriberi mainly involving central nervous system is known as dry beriberi Mixed beriberi is more common in which different systems are involved in varying degrees
  37. 37. Infantile beriberi can occur when mother is deficient in thiamin It usually occurs between two and six months of age It is mainly the wet form of beriberi with pronounced oedema
  38. 38. Vomiting, diarrhoea, hoarseness and weight loss are common in infantile beriberi The disease responds promptly to thiamin administration
  39. 39. Laboratory findings in beriberi are: • Increased pyruvic acid level in blood • Decreased thiamin concentration in RBCs • Decreased transketolase activity in RBCs
  40. 40. Riboflavin was known in the past as vitamin B2 It is heat-stable in neutral and acidic medium but not in basic medium Its aqueous solution is unstable in sunlight and ultraviolet light Riboflavin
  41. 41. Chemically, riboflavin is 6,7-dimethyl-9-D- ribityl isoalloxazine Riboflavin can be readily reduced to leucoriboflavin
  42. 42. Riboflavin (6,7-dimethyl-9-D-ribityl isoalloxazine) H C—3 || 1 2 45 6 7 8 9 10 CH —C—C—C—CH OH2 2 H | OH | OH | OH | H | H | 3 NN N H C—3 O NH O NH N
  43. 43. Functions Riboflavin functions in the form of two coenzymes: Flavin mononucleotide (FMN) Flavin adenine dinucleotide (FAD)
  44. 44. FMN and FAD can undergo reversible oxidation and reduction They participate in a number of oxidation- reduction reactions as coenzymes Riboflavin portion of FMN and FAD can reversibly combine with two hydrogen atoms
  45. 45. H C—3 || CH — C — C — C — CH — O — P — OH2 2 H | OH | OH | OH | H | H | NN N H C—3 O NH O || | OH H C —3 || H NN N H H C —3 O NH FMNH2 FMN AH2 A CH — C — C — C — CH — O — P — OH2 2 H | OH | OH | OH | H | H | O || | OH O O FMN FMNH2 H H
  46. 46. FMN is a: Constituent of respiratory chain Constituent of microsomal hydroxylase system Coenzyme for L-amino acid oxidase EMB-RCG
  47. 47. HC—3 || NN N HC—3 O NH FAD HC—3 || N HC—3 O NH H N N H AH 2 A N N N N NH 2 NH 2 H | OH | OH | OH | OH | H | H | O || CH— C — C — C — CH— O — P — O — P — O — CH222 OH | O || | | N N OH OH H H OH OH H H H H H H O O N N FADH 2 H | OH | OH | OH | OH | H | H | O || CH— C — C — C — CH— O — P — O — P — O — CH222 OH | O || O O FAD FADH2 AH2 A H H
  48. 48. FAD is a: Constituent of respiratory chain Constituent of microsomal hydroxylase system Coenzyme for many enzymes EMB-RCG
  49. 49. Some enzymes requiring FAD as a coenzyme are: • D-Amino acid oxidase • Acyl CoA dehydrogenase • Succinate dehydrogenase • Glycerol-3-phosphate dehydrogenase • Xanthine oxidase • Sphingosine reductase • Pyruvate dehydrogenase • a-Ketoglutarate dehydrogenase
  50. 50. Dietary sources of riboflavin Milk Dairy products Eggs Meat Nuts Leafy vegetables Kidney Liver
  51. 51. The recommended daily allowance (RDA) for riboflavin is 0.6 mg/1,000 kcal Or it is 2 mg/day for adults Requirement
  52. 52. An isolated deficiency of riboflavin is rare It is generally combined with other deficiencies Deficiency
  53. 53. Angular stomatitis (fissures at the angles of mouth) Cheilosis (cracked and swollen lips) Glossitis (swollen, painful, magenta-coloured tongue) Seborrheic dermatitis (rough and scaly skin) Corneal vascularisation (growth of blood vessels into the cornea) Clinical features of deficiency are:
  54. 54. Angular stomatitis and glossitis
  55. 55. Laboratory diagnosis of riboflavin deficiency is difficult Serum and urinary riboflavin are low in severe deficiency Erythrocyte riboflavin is decreased The urinary excretion of riboflavin after a test dose is decreased
  56. 56. Niacin was known in the past as anti- pellagra factor, pellagra-preventing factor and vitamin B3 It occurs in two forms, niacin (nicotinic acid) and niacinamide (nicotinamide) Niacin
  57. 57. Niacin and niacinamide are equally active Niacin is converted into niacinamide in the body
  58. 58. Niacin (nicotinic acid) Niacinamide (nicotinamide) N N –COOH –CONH2
  59. 59. Functions Niacin performs its functions in the form of two coenzymes: Nicotinamide adenine dinucleotide (NAD) Nicotinamide adenine dinucleotide phosphate (NADP)
  60. 60. Nicotinamide combines with ribose and phosphoric acid to form a nucleotide This combines with an adenine nucleotide to form a dinucleotide
  61. 61. — CONH2 CH — O — P — O — P — O — CH2 2 NN + N NH2 | N OH*OH HH OHOH HH H H HH OO N OH | OH | O O || || NAD (in NADP, —OH* is esterified with phosphoric acid) Nicotinamide adenine dinucleotide (NAD)
  62. 62. — CONH2 CH — O — P — O — P — O — CH2 2 NN + N NH2 | N OH*OH HH OHOH HH H H HH OO N OH | OH | O O || || NAD (in NADP, —OH* is esterified with phosphoric acid) OH Ι P Ι =‒ OHO Nicotinamide adenine dinucleotide phosphate (NADP)
  63. 63. NAD and NADP can undergo reversible oxidation and reduction They can act as coenzymes for several oxido-reductases CH CHC — CONH2 C — CONH2 N | R + N | R CH CHCH CH CH CH2 NAD (or NADP ) + + NADH (or NADPH) AH2 A + H + CH2CH N+
  64. 64. NAD and NADP act as coenzymes in many metabolic pathways such as: • Glycolysis • Hexose monophosphate shunt • Citric acid cycle • Synthesis of fatty acids and steroids • Oxidation of fatty acids • Oxidative deamination of amino acids
  65. 65. NAD generally acts as coenzyme in catabolic pathways NADP generally acts as coenzyme in anabolic pathways
  66. 66. Some enzymes which require NAD as a coenzyme are: • Lactate dehydrogenase • Pyruvate dehydrogenase • Isocitrate dehydrogenase • a-Ketoglutarate dehydrogenase • Malate dehydrogenase • b-Hydroxyacyl CoA dehydrogenase • Glutamate dehydrogenase • IMP dehydrogenase
  67. 67. NAD is also a constituent of: Respiratory chain Microsomal hydroxylase system
  68. 68. Examples of enzymes requiring NADP as a coenzyme are: • Glucose-6-phosphate dehydrogenase • 6-Phosphogluconate dehydrogenase • b-Ketoacyl CoA reductase • a,b-Unsaturated acyl CoA reductase • Squalene synthetase • Cholesterol 7-a-hydroxylase • Thioredoxin reductase • Haem oxygenase
  69. 69. Sources of niacin Eggs Fish Tomatoes Green leafy vegetables Milk Meat
  70. 70. Niacin is also synthesized in human beings from tryptophan It has been shown that 1 mg of niacin is synthesized from 60 mg of tryptophan
  71. 71. Pyridoxal phosphate is required as a coenzyme for synthesis of niacin Excess of leucine inhibits the conversion of tryptophan into niacin
  72. 72. The daily requirement for niacin is 6.6 mg/1,000 kcal Or the adult requirement can be taken as 20 mg/day Requirement
  73. 73. Deficiency of niacin causes pellagra Clinical features are stomatitis, glossitis, diarrhoea, dermatitis and dementia If untreated, the disease can be fatal Deficiency
  74. 74. Dermatitis usually affects the exposed parts of the body
  75. 75. Dermatitis in pellagra
  76. 76. Pellagra is common in people consuming maize and sorghum as their staple food These two are poor in niacin and tryptophan, and rich in leucine
  77. 77. Pantothenic acid was known in the past as vitamin B5 It is heat-stable in neutral medium but not in acidic or basic medium It is not destroyed by oxidizing or reducing agents Pantothenic acid
  78. 78. Pantoic acid Pantothenic acid b-Alanine Pantothenic acid is made up of pantoic acid and b-alanine
  79. 79. Functions • Coenzyme A (CoA) • Acyl carrier protein (ACP) Pantothenic acid performs its functions as a constituent of: Both these contain pantothenic acid in the form of 4’-phosphopantetheine
  80. 80. Pantothenic acid is first phosphorylated at C4 of the pantoic acid residue The product is 4’-phosphopantothenic acid This combines with cysteine to form 4’- phosphopantothenyl cysteine
  81. 81. CH — C — CH — C — N — CH — CH —2 2 2 C — N — CH — CH — SH2 CH3 | H | H | COOH | O || O || CH3 | || OHO | O = P — OH 4´-Phosphopantothenic acid Cysteine 4´-Phosphopantothenyl cysteine | OH
  82. 82. Decarboxylation of the cysteine residue converts 4’-phosphopantothenyl cysteine into 4’-phosphopantetheine 4’-Phosphopantetheine is linked with AMP to form dephosphocoenzyme A Ribose moiety of dephosphocoenzyme A is phosphorylated at C3 to form coenzyme A
  83. 83. N N NH2 | N OH H O H H N O = P — OH H | | CH2 | O = P — OH CH C CH C N CH CH2 2 2— — — — — — — C — N — CH — CH — SH2 2 CH3 | H | H | O || O || CH3 | | OH | O | | O O | O = P — OH | O Coenzyme A N NN N O
  84. 84. In ACP, 4’-phosphopantetheine is esterified with a serine residue of the protein The –SH group of 4’-phosphopantetheine remains free
  85. 85. Coenzyme A is also represented as CoA- SH as its terminal –SH group binds various compounds Coenzyme A participates in a variety of reactions in the metabolism of carbo- hydrates, lipids and amino acids Role of Coenzyme A
  86. 86. Examples of reactions requiring coenzyme A are: • Oxidative decarboxylation of a-keto acids • Activation of fatty acids • Activation of some amino acids
  87. 87. A number of coenzymes are required in this multi-step reaction Coenzyme A is one of them Oxidative decarboxylation of a-keto acids
  88. 88. R ‒ C ‒ COOH + CoA‒SH + NAD+ O ‖ R ‒ C ~ S‒CoA + NADH + H+ + CO2 O ‖ a-Keto acid Acyl CoA Oxidative decarboxylation
  89. 89. Pyruvate is converted into acetyl CoA by oxidative decarboxylation a-Ketoglutarate is converted into succinyl CoA by oxidative decarboxylation
  90. 90. Before fatty acids can take part in any reaction, they have to be converted into their CoA derivatives This reaction, known as activation of fatty acids, is catalysed by acyl CoA synthetase (thiokinase) Activation of fatty acids
  91. 91. R ‒ CH2 ‒ COOH + CoA‒SH + ATP R ‒ CH2 ‒ C ~ S‒CoA + AMP + PPi O ‖ Fatty acid Acyl CoA Activation of fatty acid
  92. 92. Some amino acids are converted into their CoA derivatives before they can be metabolized Examples are leucine, isoleucine and valine Activation of amino acids
  93. 93. An important role of CoA is to provide active acetate (acetyl CoA) Active acetate is required for synthesis of fatty acids, cholesterol, ketone bodies, acetylcholine etc
  94. 94. Coenzyme A also forms active succinate (succinyl CoA) Active succinate is required for haem synthesis and for gluconeogenesis from some amino acids
  95. 95. Pantothenic acid is a constituent of acyl carrier protein (ACP) also ACP is a part of the multienzyme complex which catalyses de novo synthesis of fatty acids Role of acyl carrier protein
  96. 96. Pantothenic acid is widely distributed in animal and plant foods It is also synthesized by intestinal bacteria Sources
  97. 97. Dietary sources of pantothenic acid LiverKidney Meat Eggs Wheat Peas Sweet potatoes Yeast
  98. 98. The recommended daily intake is 10 mg A smaller intake may be sufficient for infants and children Requirement
  99. 99. Deficiency of pantothenic acid has not been reported in human beings In animals, deficiency causes loss of weight, loss of hair, greying of hair, anaemia and necrosis of adrenal glands Deficiency
  100. 100. Human deficiency can be produced experimentally It leads to neurological and gastrointestinal disturbances
  101. 101. Pyridoxine was known in the past as vitamin B6 It consists of three closely related pyridine derivatives These are pyridoxine, pyridoxal and pyridoxamine All the three are equally active as vitamins Pyridoxine
  102. 102. CH OH | 2 CHO | CH NH2 2 | —CH OH2 —CH OH2 —CH OH2HO— HO— HO— H C—3 H C—3 H C—3 N N N Pyridoxine Pyridoxal Pyridoxamine N N N
  103. 103. Pyridoxine, pyridoxal and pyridoxamine are converted into coenzymes The conzymes are: • Pyridoxine phosphate • Pyridoxal phosphate • Pyridoxamine phosphate Functions
  104. 104. Pyridoxine, pyridoxal and pyridoxamine are phosphorylated by a common enzyme The three coenzymes are interconvertible The phosphate group is provided by ATP The enzyme is pyridoxal kinase
  105. 105. N HO‒ H3C‒ ‒CH2OH CH2OH Ι CH2OH Ι HO‒ H3C‒ ‒CH2‒O‒P‒OH + ATP + ADP ‖ O OH Pyridoxine Pyridoxine phosphate Pyridoxal kinase N I
  106. 106. N HO‒ H3C‒ ‒CH2OH CHO I CHO I HO‒ H3C‒ ‒CH2‒O‒P‒OH + ATP + ADP ‖ O OH Pyridoxal Pyridoxal phosphate Pyridoxal kinase N I
  107. 107. N HO‒ H3C‒ ‒CH2OH CH2NH2 I CH2NH2 I HO‒ H3C‒ ‒CH2‒O‒P‒OH + ATP + ADP ‖ O OH Pyridoxamine Pyridoxamine phosphate Pyridoxal kinase N I
  108. 108. Vitamin B6 coenzymes are required mainly in the metabolism of amino acids Pyridoxal phosphate (PLP) can form a Schiff base with an amino acid
  109. 109. Schiff base The amino acid, thus bound, can undergo various reactions Ι ‖ Ι H3C‒ HO‒ ‒CH2‒O‒ P C‒H R‒CH‒COOH N N
  110. 110. The amino acid bound to pyridoxal phosphate can undergo: • Transamination • Deamination • Decarboxylation • Transulphuration • Desulphydration
  111. 111. Pyridoxal phosphate is also required in: • Metabolism of tryptophan • Synthesis of haem • Cellular uptake of amino acids • Formation of g-amino butyric acid • Glycogenolysis
  112. 112. These reactions are catalysed by specific transaminases The amino group of an amino acid is transferred to an a-keto acid This results in the formation of a new amino acid and a new a-keto acid PLP acts as a carrier of the amino group Transamination
  113. 113. Transamination reactions are important in: • Formation of new amino acids • Catabolism of amino acids
  114. 114.  Subjects deficient in thiamin retain most of the test dose in tissues and excrete less in urine  Measurement of transketolase activity in erythrocytes can confirm the diagnosis NH2 NH2 | | R — CH — COOH1 R — C — COOH1 R — CH — COOH2 CHO | | HO— HO— H C—3 H C—3 N N —CH O — P2— —CH O — P2— CH NH2 2 Amino acid Pyridoxal phosphate Pyridoxamine phosphate Amino acid a-Keto acid O || R — C — COOH2 a-Keto acid O || N N
  115. 115. Deamination PLP acts as a coenzyme for: • Serine deaminase • Threonine deaminase
  116. 116. Decarboxylation PLP is a coenzyme for decarboxylases acting on: • Glutamate • Arginine • Tyrosine
  117. 117. PLP is a coenzyme for cystathionine synthetase and cystathionine g-lyase These two transfer sulphur from homocysteine to serine forming cysteine Transulphuration
  118. 118. PLP is a coenzyme for cysteine desulphydrase This enzyme removes the sulphydryl group from cysteine Desulphydration
  119. 119. One of the intermediates in the catabolism of tryptophan is 3-hydroxykynurenine This is converted into 3-hydroxyanthranilic acid by kynureninase, a PLP-dependent enzyme Tryptophan metabolism
  120. 120. When PLP is not available, 3-hydroxy- anthranilic acid is not formed 3-Hydroxykynurenine is spontaneously converted into xanthurenic acid Xanthurenic acid, which is an alternate metabolite, is excreted in urine
  121. 121. Tryptophan 3-Hydroxy- kynurenine Kynureninase 3-Hydroxy- anthranilic acid Excreted in urineAcetoacetyl CoA Xanthurenic acid Sponta- neous Urinary xanthurenic acid excretion is an indicator of pyridoxine deficiency PLP In the presence of PLP In absence of PLP
  122. 122. One of the enzymes involved in the synthesis of haem is d-aminolevulinic acid synthetase This enzyme requires PLP as a coenzyme Synthesis of haem
  123. 123. Cellular uptake of L-amino acids is an active process This requires the participation of pyridoxal phosphate Cellular uptake of amino acids
  124. 124. Gamma-amino butyric acid (GABA) acts as a neurotransmitter in brain It is formed by the action of glutamate decarboxylase on glutamate PLP is required as a coenzyme in this reaction Formation of g-amino butyric acid
  125. 125. Phosphorylase is a key enzyme of glyco- genolysis Phosphorylase requires PLP as a coenzyme Glycogenolysis
  126. 126. Sources of pyridoxine include animal as well as plant foods Another source is bacterial synthesis in the intestine Sources
  127. 127. Dietary sources of pyridoxine Leafy vegetables Meat Eggs Milk Wheat Corn Beans Potato Bananas
  128. 128. Pyridoxine is mainly required in the metabolism of amino acids Its requirement depends upon the protein intake An intake of 1.25 mg/100 gm of proteins has been recommended Requirement
  129. 129. Deficiency is very rare It may sometimes occur in infants and pregnant women Deficiency may also occur in patients taking isoniazid, an anti-tuberculosis drug Isoniazid forms a complex with pyridoxal and prevents its activation Deficiency
  130. 130. Clinical features of pyridoxine deficiency are: • Nausea • Vomiting • Dermatitis • Microcytic anaemia • Convulsions Convulsions are more common in children while anaemia is more common in adults
  131. 131. Chronic pyridoxine deficiency may cause hyperhomocysteinaemia Hyperhomocysteinaemia increases the risk of cardio-vascular diseases
  132. 132. Urinary excretion of xanthurenic acid is increased in pyridoxine deficiency Measuring xanthurenic acid excretion Giving a test dose of tryptophan Pyridoxine deficiency can be diagnosed by:
  133. 133. Biotin is also known as anti-egg white injury factor When raw egg white is fed to rats, they develop some symptoms which are relieved by biotin Biotin
  134. 134. It has been shown that raw egg white contains a protein, avidin Avidin forms a complex with biotin preventing its intestinal absorption This leads to a deficiency of biotin
  135. 135. Avidin is inactivated by heat Therefore, cooked eggs do not hamper absorption of biotin Biotin is heat-stable
  136. 136. Biotin is a heterocyclic sulphur-containing monocarboxylic acid HN | HC | H2C NH | CH | CH — (CH2)4— COOH O || C S
  137. 137. Biotin is a coenzyme for carboxylases It is also known as co-carboxylase Biotin is firmly bound to the enzyme ‒COOH group of biotin is bonded with e-NH2 group of a lysine residue of enzyme Functions
  138. 138. Some carboxylation reactions requiring biotin are: Carboxylation of pyruvate Carboxylation of acetyl CoA Carboxylation of propionyl CoA EMB-RCG
  139. 139. This reaction converts pyruvate into oxalo- acetate Oxaloacetate is an intermediate in citric acid cycle This reaction is important for the normal operation of citric acid cycle Carboxylation of pyruvate
  140. 140. CH3 | C = O | COOH + CO2 + ATP Pyruvate COOH | CH2 | C = O | COOH + ADP + Pi Oxaloacetate Pyruvate carboxylaseBiotin
  141. 141. Carboxylation converts acetyl CoA into malonyl CoA This reaction is important in fatty acid synthesis Carboxylation of acetyl CoA
  142. 142. Carboxylation of acetyl CoA CH3— C ~ S — CoA + CO2 + ATP CH2— C ~ S — CoA + ADP + Pi Acetyl CoA Malonyl CoA Acetyl CoA carboxylase Biotin O || O || COOH |
  143. 143. Propionyl CoA is carboxylated to D-methyl- malonyl CoA This is one of the reactions in the gluco- neogenic pathway for conversion of propionate into glucose Carboxylation of propionyl CoA
  144. 144. CH3 CH3 | | CH2 H — C — COOH | | O = C ~ S — CoA + CO2 + ATP O = C ~ S — CoA + ADP + Pi Propionyl CoA D-Methylmalonyl CoA Propionyl CoA carboxylaseBiotin
  145. 145. Bacterial synthesis in the intestine provides sufficient amounts of biotin Dietary sources include animal foods as well as plant foods Sources
  146. 146. CauliflowerAvocado Berries Eggs Meat Nuts Sources of biotin
  147. 147. Biotin requirement is not known with certainty as the intestinal bacteria meet most of the requirement The daily intake has been estimated to be 100 to 300 mg Requirement
  148. 148. Deficiency of biotin is unknown in human beings Deficiency may occur in animals when they are fed raw egg white Deficiency
  149. 149. Clinical features of biotin deficiency in animals are: • Retarded growth • Loss of weight • Dermatitis • Loss of hair • Muscular inco-ordination • Paralysis
  150. 150. Folic acid is also known as folacin or pteroylglutamic acid It is made up of pteridine, para-amino- benzoic acid and glutamic acid Folic acid
  151. 151. H N2 N N | OH 1 2 3 4 N 5 6 7 8 N 9 10 CH — N —2 — C — N — CH | | H COOH COOH | CH2 | CH2 | O || H | Pteridine para-Amino- benzoic acid Glutamic acid Pteroylgutamic acid (folic acid)
  152. 152. Folic acid is found in food as pteroyl monoglutamate, pteroyl triglutamate and pteroyl heptaglutamate The last two are converted into pteroyl monoglutamate in the intestinal mucosa Folic acid is heat-stable in neutral medium
  153. 153. Folic acid functions as a coenzyme, tetrahydrofolate (H4-folate or FH4) Folate is first reduced to 7,8-dihydrofolate (H2-folate or FH2) 7,8-Dihydrofolate is, then, reduced to 5,6,7,8-tetrahydrofolate Functions
  154. 154. Dihydrofolate Tetrahydrofolate Folate Dihydrofolate reductase Dihydrofolate reductase NADPH + H+ NADPH + H+ NADP+ NADP+
  155. 155. Amethopterin and aminopterin are competitive inhibitors of dihydrofolate reductase They act as folic acid antagonists or folic acid anti-metabolites
  156. 156. H4-Folate is a carrier of one-carbon units The one-carbon unit may be attached to N5 or N10 of H4-folate
  157. 157. The one-carbon units carried by H4- folate may be: • Formyl (–CHO) group • Formate (–HCOO‒) group • Methyl (–CH3) group • Methylene (=CH2) group • Methenyl (=CH) group • Formimino (–CH=NH) group
  158. 158. H N2 N N N H 5 H N 10 CH — N —2 — C — N — CH | | CHO COOH COOH | CH2 | CH2 | O || H | H N2 N N N | CH3 5 H N 10 CH — N —2 — C — N — CH | | H COOH COOH | CH2 | CH2 | O || H | N -Methyl-H -folate 5 4 N -Formyl-H -folate (f -H -folate) 10 10 4 4 H N2 N N N | CH || NH 5 H N 10 CH — N —2 — C — N — CH | | H COOH COOH | CH2 | CH2 | O || H | N -Formimino-H -folate (fi -H -folate)5 5 4 4 | OH | OH | OH
  159. 159. H4-Folate can: • Receive one-carbon units from various compounds • Transfer one-carbon units to various compounds
  160. 160. Sources of one-carbon units Tetrahydrofolate may receive one-carbon units from: • Formiminoglutamic acid • Methionine • Choline • Thymine • Serine
  161. 161. Formiminoglutamic acid (FIGLU) is formed in the body from histidine: Histidine → Urocanic acid → → FIGLU FIGLU can transfer its formimino group to tetrahydrofolate: FIGLU+ H4-Folate → fi5-H4-Folate + Glutamate
  162. 162. Methionine, choline and thymine are the source of methyl groups Serine can contribute its hydroxymethyl group
  163. 163. Utilization of one-carbon units The one-carbon unit carried by tetra- hydrofolate can be used for synthesis of: • Purines • Serine • Methionine • Choline • Thymine • n-Formylmethionine
  164. 164. Synthesis of purines: The carbon atoms two and eight of purines are contributed by f10-H4- folate
  165. 165. Synthesis of serine: The hydroxymethyl group for the conversion of glycine into serine is provided by N5, N10-methylene-H4-folate
  166. 166. Synthesis of methionine: The methyl group for the conversion of homocysteine into methionine is provided by N5-methyl-H4-folate
  167. 167. Synthesis of choline: The methyl groups for the synthesis of choline from serine are provided by N10- methyl-H4-folate
  168. 168. Synthesis of thymine: The methyl group of thymine is provided by N5, N10-methylene-H4-folate
  169. 169. Synthesis of n-formylmethionine: • The formyl unit of f10-H4-folate converts methionine into n-formylmethionine • n-Formylmethionine initiates protein synthesis in prokaryotes
  170. 170. Green leafy vegetables are the major source of folic acid Folic acid is present in several other vegetables, yeast, meat, fish, milk etc Intestinal bacteria also synthesize folic acid Sources
  171. 171. Sources of folic acid Green leafy vegetables Other vegetables Fish MilkMeat Yeast
  172. 172. Requirement Infants and children 100 mg/day Adult men and women 100 mg/day Pregnant women 300 mg/day Lactating women 150 mg/day
  173. 173. Folic acid is required for the synthesis of purines and thymine Its deficiency impairs nucleic acid synthesis This leads to growth failure and megalo- blastic anaemia Leukopenia can also occur Deficiency
  174. 174. Megaloblasts in folic acid deficiency
  175. 175. Folic acid deficiency during pregnancy can cause neural tube defects in the baby This occurs very early in pregnancy Folic acid supplements are recommended from conception or even earlier
  176. 176. Neural tube defect
  177. 177. Deficiency can be diagnosed by giving a test dose of histidine Urinary excretion of FIGLU is measured after giving the test dose The excretion is increased in subjects deficient in folic acid Laboratory diagnosis
  178. 178. Vitamin B12 exists in several forms Cyanocobalamin was the first form discovered It was isolated as a red crystalline compound from liver in 1948 Cobalamin (Vitamin B12)
  179. 179. Vitamin B12 activity was found in compounds in which the cyanide group is replaced by: • Hydroxyl group (hydroxocobalamin) • Methyl group (methylcobalamin) • Nitro group (nitrocobalamin)
  180. 180. Vitamin B12 has a complex structure Molecular formula of cyanocobalamin is C63H88O14N14PCo It has four pyrrole rings with a cobalt atom at the centre (corrin ring) The tetrapyrrole is heavily reduced and substituted
  181. 181. The cobalt atom of the corrin ring forms co-ordination bonds with: • Nitrogen atoms of four pyrrole rings • Cyanide group • 5,6-Dimethylbenzimidazole
  182. 182. 5,6-Dimethylbenzimidazole is linked with ribose-3-phosphate The phosphate group of ribose-3- phosphate is linked with the pyrrole ring D (IV) through amino propanol
  183. 183. N N OH H O H H H O H C –3 H C –3 CH OH2 H N – OC – H C –2 2 HN – OC – H C – H C –2 2 | CH2 | CH – CH3 | O | O = P – OH NH2 | | CO | CH2 | CH2 | N N H C–3 H C–3 NH2 CH2 | | CO CO | | | CH2 CH2 | | A C D BN N – CH – CO – NH2 2 – CH – CH – CO – NH2 2 2| CH3 | CH3 CH3 CH3 – CH3 CH3 NH2 Co+ CN
  184. 184. Vitamin B12 is heat-stable in acidic and neutral medium It is present in food in association with proteins
  185. 185. The ingested vitamin B12 is released from proteins by gastric hydrochloric acid Most of the vitamin binds to R-proteins present in gastric juice and saliva R-Proteins are synthesized by many cells, and include transcobalamin I and trans- cobalamin III Absorption, transport and storage
  186. 186. Gastric parietal cells secrete intrinsic factor (IF) IF is a glycoprotein of 45 kD which can bind vitamin B12 At low pH, affinity of vitamin B12 for R- proteins is much higher than that for IF
  187. 187. Most of the vitamin binds to R-proteins in the stomach In duodenum, R-proteins are hydrolysed by pancreatic proteases Vitamin B12 released from R-proteins is bound to IF
  188. 188. One IF molecule binds one molecule of vitamin B12 A specific receptor on ileal mucosa binds the IF-vitamin B12 complex The vitamin is taken up by the mucosal cells and is transferred to plasma
  189. 189. Most of the vitamin is bound to trans- cobalamin II in plasma Transcobalamin II-vitamin B12 complex is taken up by cells which require vitamin B12 These cells take up the complex with the help of a specific receptor
  190. 190. Transcobalamin II is hydrolysed in the cell by lysosomal enzymes Vitamin B12 is released, mostly in the form of hydroxocobalamin It is converted into coenzymes, and is utilized in the cell
  191. 191. A significant amount of vitamin B12 is stored in the body In well-nourished adults, vitamin B12 stores are about 2,000-5,000 mg About 60% of the vitamin is stored in liver, mostly bound to transcobalamin III
  192. 192. Vitamin B12 forms coenzymes known as cobamides (B12 coenzymes) The coenzymes are formed by replace- ment of the cyanide or hydroxyl group The major B12 coenzymes are methyl- cobalamin and adenosylcobalamin Functions
  193. 193. In methylcobalamin, the cyanide group is replaced by a methyl group In adenosylcobalamin, it is replaced by 5´- deoxyadenosine
  194. 194. Methylcobalamin Adenosylcobalamin
  195. 195. The cobamides function as coenzymes, mainly in the transfer of one-carbon units They complement the function of tetra- hydrofolate
  196. 196. Besides H4-folate, cobamides are also involved in transfer of one-carbon units An example of one such reaction is synthesis of methionine from homocysteine Transfer of one-carbon units
  197. 197. H4-FolateN5-Methyl-H4-folate MethylcobalaminCobalamin Methionine Homocysteine H4-Folate released in this reaction returns to the folate pool It can again participate in one-carbon transfer reactions
  198. 198. In cobalamin deficiency, H4-folate cannot return to folate pool It is trapped as methyl-H4-folate (known as folate trap) Thus, cobamides help by sharing a part of the load on H4-folate
  199. 199. Adenosylcobalamin acts as a coenzyme in the conversion of methylmalonyl CoA into succinyl CoA Methylmalonyl CoA is formed mainly from isoleucine, valine and methionine It is also formed from fatty acids having an odd number of carbon atoms Formation of succinyl CoA
  200. 200. CH3 | HOOC — C — H | C ~ S — CoA Methylmalonyl CoA isomeraseCobamide L-Methylmalonyl CoA Succinyl CoA || O | CH — C ~ S — CoA2 || O CH — COOH2
  201. 201. Succinyl CoA may be: • Converted into glucose or • Oxidized in citric acid cycle
  202. 202. In vitamin B12 deficiency, methylmalonic acid is excreted in large amounts in urine (methylmalonic aciduria) Rarely, methylmalonic aciduria may be caused by an inherited defect in methylmalonyl CoA isomerase
  203. 203. Vitamin B12 cannot be synthesized by any plant or animal It is synthesized only by some bacteria Animals acquire it through bacterial synthesis in their intestines Bacteria present in the human intestine also synthesize vitamin B12 Sources
  204. 204. Dietary sources of vitamin B12 Eggs Liver Kidney Meat Cheese Milk
  205. 205. Requirement Age and sex Requirement Infants and children 0.2-1 µg/day Adult men and women 1 µg/day Pregnant and lactating women 1.5 µg/day
  206. 206. Deficiency Deficiency of vitamin B12 is historically associated with pernicious anaemia The disease is also known as Addison- Biermer anaemia It was a fatal disease before liver was introduced for its treatment in 1926
  207. 207. A prescription for pernicious anaemia in 1936
  208. 208. Liver was believed to have an anti- pernicious anaemia factor (APAF) Castle (1930) showed that stomach produced a compound necessary for absorption of APAF He named this compound as the intrinsic factor, and APAF as the extrinsic factor
  209. 209. The extrinsic factor later turned out to be vitamin B12 The basic cause of pernicious anaemia was found to be absence of intrinsic factor Autoimmune destruction of gastric parietal cells leads to absence of intrinsic factor
  210. 210. Clinical features of deficiency may take long to develop Hepatic stores of vitamin B12 can last several years The deficiency affects the haemopoietic system and the nervous system
  211. 211. The characteristic haematological feature is megaloblastic anaemia Large and immature red cell precursors are released into circulation This is done to compensate ineffective haemopoiesis
  212. 212. Involvement of nervous system causes sub-acute combined degeneration (SACD) This is degeneration of dorsal and lateral columns of spinal cord
  213. 213. Postrior column Lateral column SACD Anterior column Degeraration Normal
  214. 214. SACD leads to sensory as well as motor disturbances Numbness, tingling, sore tongue and ataxia are common neurological features Psychiatric abnormalities can also occur The neuropathy is believed to be due to accumulation of methylmalonic acid
  215. 215. Deficiency of vitamin B12 is not always due to pernicious anaemia It can also occur due to deficient intake or decreased absorption Such deficiency causes megaloblastic anaemia but not neuropathy
  216. 216. Ascorbic acid Ascorbic acid (vitamin C) prevents a specific deficiency disease, scurvy Therefore, it is also known as anti- scorbutic factor It is very heat-labile, specially in basic medium
  217. 217. Chemically, the structure of ascorbic acid resembles that of hexoses Like hexoses, it can exist as L- and D- isomers Only L-isomer possesses vitamin activity
  218. 218. Ascorbic acid can be readily oxidized to dehydroascorbic acid L-Ascorbic acid and L-dehydroascorbic acid possess equal vitamin activity
  219. 219. C = O | C – OH || C – OH | H – C | HO – C – H | CH OH2 H – C C = O | | | | HO – C – H | CH OH2 C = O C = O L-Ascorbic acid L-Dehydroascorbic acid O O
  220. 220. Vitamin C is synthesized by all plants and animals via uronic acid pathway Exceptions are guinea pigs and primates which require vitamin C from outside Guinea pigs and primates lack L-gulono- lactone oxidase This enzyme converts L-gulonolactone into L-ascorbic acid
  221. 221. From an average diet, 70 to 95% of the ingested ascorbic acid is absorbed However, as the intake increases, the proportion of absorption decreases
  222. 222. Cells take up vitamin C with the help of some transporters The transporters involved in cellular uptake are: • Sodium-Vitamin C Transporters (SVCTs) • Glucose Transporters (GLUTs)
  223. 223. SVCT1 and SVCT2 are active transport systems for vitamin C Transport by SVCT1 and SVCT2 is sodium-linked GLUT1 and GLUT3 transport vitamin C by facilitated diffusion
  224. 224. SVCT1 and SVCT2 transport the reduced form (ascorbic acid) into the cells GLUT1 and GLUT3 transport the oxidized form (dehydroascorbic acid) into the cells SVCT2 transports vitamin C in all the tissues with the exception of erythrocytes
  225. 225. Tissue distribution Total amount of ascorbic acid in an adult is 2-3 gm It is distributed in all tissues and body fluids It is present in high concentrations in the glands
  226. 226. The highest concentration is found in the adrenal glands followed by other glands The concentration in plasma is 0.5-1.5 mg/dl The vitamin begins to appear in urine when the plasma level exceeds 1.5 mg/dl
  227. 227. Functions Ascorbic acid can undergo reversible oxidation and reduction Hence, ascorbic acid acts as a coenzyme in some oxidation-reduction reactions
  228. 228. C = O | C – OH || C – OH | H – C | HO – C – H | CH OH2 H – C C = O | | | | HO – C – H | CH OH2 C = O C = O L-Ascorbic acid (reduced) L-Dehydroascorbic acid (oxidized) O O A AH2
  229. 229. Ascorbic acid is required for the synthesis of: • Collagen • Carnitine • Neurotransmitters • Tyrosine etc
  230. 230. Ascorbic acid acts as a coenzyme for prolyl hydroxylase and lysyl hydroxylase These two hydroxylate proline and lysine residues in the newly synthesized collagen Hydroxylation allows collagen molecule to mature and assume its triple helix structure
  231. 231. Hence, it is essential for the formation and maintenance of: • Matrix of bones • Cartilages • Dentine • Blood vessels • Scar tissue etc Ascorbic acid plays an important role in post-translational modification of collagen
  232. 232. Ascorbic acid is a coenzyme for e-N- trimethyl-lysine hydroxylase and g-butyro- betaine hydroxylase These two are necessary for synthesis of carnitine
  233. 233. Ascorbic acid is a coenzyme for dopamine b-hydroxylase This enzyme participates in the synthesis of norepinephrine and epinephrine from dopamine
  234. 234. Ascorbic acid is a coenzyme for para- hydroxyphenylpyruvate hydroxylase Thus, it participates in the catabolism of tyrosine
  235. 235. Ascorbic acid is a coenzyme for peptidyl- glycine a-amidating mono-oxygenase This enzyme adds amide groups to several peptide hormones This addition greatly increases their stability
  236. 236. Ascorbic acid is required for the formation of bile acids from cholesterol Cholesterol is converted into 7-a-hydroxy- cholesterol for bile acid synthesis This reaction, catalysed by cholesterol 7-a- hydroxylase, requires ascorbic acid
  237. 237. Ascorbic acid is a reductant, and keeps iron and copper in reduced state By converting ferric ions into ferrous ions, it helps in the intestinal absorption of iron
  238. 238. Ascorbic acid also acts as an anti-oxidant Along with other anti-oxidants, it helps in combating oxidative stress
  239. 239. Sources Indian gooseberry (amla) is the richest source of vitamin C All citrus fruits are rich in vitamin C Several other fruits and vegetables are good sources
  240. 240. Sources of vitamin C Green leafy vegetables CauliflowerTomatoes Berries Amla OrangeLemon Kiwi
  241. 241. Considerable losses of vitamin C can occur during cooking Hence, some raw fruits and salads should be included in the daily diet
  242. 242. Requirement Age and sex RDA (ICMR, 2010) Infants 25 mg/day Children and adults 40 mg/day Pregnant women 60 mg/day Lactating women 80 mg/day
  243. 243. Deficiency Deficiency of vitamin C produces scurvy A full-blown picture of scurvy is rare these days Isolated signs and symptoms of vitamin C deficiency are still seen
  244. 244. Signs and symptoms of scurvy include: • Swollen, spongy and bleeding gums • Loosening of teeth • Petechial haemorrhages • Anaemia • Retardation of skeletal growth • Easy fracturability of bones • Delayed union of fractures • Delayed healing of wounds
  245. 245. Bleeding gums in vitamin C deficiency
  246. 246. Petechial haemorrhages
  247. 247. Laboratory diagnosis of deficiency can be made by ascorbic acid saturation test After a test dose of ascorbic acid, urinary excretion of ascorbic acid is measured The excretion is low in subjects deficient in vitamin C

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