M.

Prasad Naidu
MSc Medical Biochemistry, Ph.D,.

Objectives:
Definition of Vitamins
Classification of Vitamins
1. water soluble
2. Fat soluble
Diferenses between water soluble vitamins & Fat
soluble vitamins
Vitamin like compounds
Provitamins
Antivitamins
Hypervitaminosis




When we speak and write individual vitamins under
the following headings.

Chemistry
Sources
RDA
Co-enzyme or active form
Biochemical functions
Causes of deficiency
Deficiency manifestations
Assay





Water Soluble vitamins

Sulphur containing vitamin

Synonyms:
Anti-beriberi factor , anti-neuritic vitamin,
aneurin.
PLANT SOURCES:
Rich source- ALEURONE LAYER of cereals .
Good sources unpolished rice ,
whole wheat, peas,beans

ANIMAL SOURCES:
Liver , meat , eggs

RECOMMENDED DIETARY ALLOWANCE(RDA):
Depends on intake of carbohydrates -0.5mg/1000cal

ADULTS 1 -1.5 mg/ day
Requirement increased in
Old age, pregnancy ,lactation and alcoholism.



Formed by addition of two phosphate
groups with help of ATP and enzyme
thiamine- pyrophosphate transferase.

BIOCHEMICAL FUNCTIONS:
A .Involved in carbohydrate metabolism.
1. Pyruvate dehydrogenase oxidative
decarboxylation of pyruvate.

CoA.SH PDH CO2
Pyruvate acetylCoA
NAD
+
TPP NADH + H+
2. -ketoglutarate dehydrogenase
Oxidativedecarboxylation of alpha ketoglutarate in TCA
cycle
CoA.SH CO2

lpha-ketogluatarate Succinyl co A

NAD
+
TPP NADH + H+
B. OXIDATIVE DECARBOXYLATION OF
BRANCHED CHAIN AMINOACIDS
Branched chain aminoacids (leucine, isoleucine ,valine)

Corresponding alpha keto acids
NAD+, CoASH TPP
alpha keto acid dehydrogenase
NADH +H
+
, CO2
Corressponding alpha,beta unsaturated acyl CoA

D. Nerve transmission:

TPP is required for Acetylcholine synthesis and
in ion translocation of neural tissue.

Pyruvate acetyl CoA


acetyl choline
Deficiency of thiamine leads to BERI-BERI
Early stages GIT symptoms like anorexia, irritability,
decreased gastric motility, nausea , vomiting.

Prolonged deficiency leads to Beri-beri.
a) Dry beriberi: associated with neurological
symptoms resulting in peripheral neuritis


Basis for neuritic symptoms:
TPP is an important coenzyme in the PYRUVATE-
DEHYDROGENASE COMPLEX.(PDH)
PDH acts as a link between Glycolysis and citric- acid
cycle.
These two pathways are central to glucose utilisation
,thiamine deficiency leads to IMPAIRED GLUCOSE
UTILISATION .
IMPAIRMENT of GLUCOSE UTILISATION is likely to
affect nervous system that is dependent heavily on
glucose for its energy requirements.
b)Wet beri-beri :

Characterised by Cardiovascular symptoms that
include edema of face and legs, palpitation , and
dyspnea that progresses to heart failure.

This is due to impaired myocardial energy
metabolism .

Basis for odema in Wet Beri-Beri:
PDH
Pyruvate acetyl CoA

LACTIC ACID

Accumulation of pyruvate and lactic acid produces

vasodilatation as both are acidic products.

A rapid blood flow occurs through dilated

capillaries,resulting in increased cardiac output.





Vasodilatation and hyperdynamic circulation promote
extravasation of intravascular fluid through the
capillary walls to produce EDEMA.

As the disease progresses , the excessive strain on
myocardium leads to muscle hypertrophy and hence cardiac
enlargement. This is further increased, because the
overworked tissue cannot use glucose efficiently as an energy
substrate.
WERNICKE KORSAKOFFs syndrome:
Seen in chronic alcoholics.

Characterised by encephalopathy
(opthalmoplegia, nystagmus,cerebellar- ataxia) +
memory loss + psychosis.

Basis: Increrased demand of thiamine

Alcohol inhibits intestinal absorption of
thiamine.

Diagnosis of B1 DEFECIENCY:
Thiamine or its metabolites excretion in urine after
a loading dose of thiamine.(lower excretion seen in
deficiency).

MEASUREMENT OF RBC TRANSKETOLASE
ACTIVITY IS a RELIABLE INDICATOR.

Lactic acid to pyruvate ratio is more specific.
Pyruvate dehydrogenase complex

Catalyzes the conversion or pyruvate to acetyl CoA.

The reaction is essential for the complete oxidation of
glucose.

The reaction links glylcolysis and citric acid cycle.

In thiamin deficiency, pyruvate and lactate are increased
in the blood due to the decreased activity of the pyruvate
dehydrogenase complex
-ketoglutarate dehydrogenase complex

catalyzes the conversion of -ketoglutarate to succinyl
CoA.
The reaction occurs in citric acid cycle.
-keto acid (branched chain) dehydrogenase complex
catalyzes the conversion of -keto acids derived from
branched chain amino acid to form corresponding acyl
CoAs.

this is a reaction of catabolism of branched chain amino
acids.
Transketolase
Catalyzes two reactions of pentose phosphate pathway
Biochemical functions:
Mainly carbohydrate metabolism
T.P.P Oxidative Decarboxylation of alpha keto
acids and Transketolase

T.P.P is a co-enzyme for Pyruvate decarboxylase
a component of pyruvate dehydrogenase
complex.
Pyruvate to Acetyl COA +co2

It is also involved in Decarboxylation of
branched chain amino acids

Transketolase;
HMP shunt produces Ribose and NADPH

nucleotides formation

NADPH reductive synthetic reactions

RDA
0.5Mg/ 1000, kcal
1 to 1.5 Mg /day
Increased in pregnancy lactation. Adults with
muscular activity, alcoholics

Deficiency manifestations
Beri Beri:
More vulnerable who take high polished rice
chronic alcoholics no proper food is taken.
pregnancy, lactation more required.

Early symptoms Constipation
Anorexia
Mental depriesion
Peripheral neuropathy
Fatigue
Late symptoms Neurological
Ataxia
Mental confusion
Loss of eye coordination
Prolonged deficiency leads to Cardiovascular and
muscular defects

Riboflavin (B2)
Sources :
Whole milk ,egg, liver, dried yeast are rich sources.

Germinating seeds are a good source.

Humans cannot synthesize but INTESTINAL BACTERIA
CAN SYNTHESIZE.

RDA:
1.5 - 1.8 mg/ day

Pregnancy,Lactation,old age - higher requirement
Flavin mononucleotide (FMN)
Flavin adenine dinucleotide (FAD)

flavokinase FAD synthase
Riboflavin FMN FAD

ATP ADP ATP PPi
Biochemical functions :
FAD dependent reactions:
1. Carbohydrate metabolism:
a) Tricarboxylic cycle (TCA)
succinate dehydrogenase
succinate +FAD fumarate+FADH2

b)oxidative decarboxylation of alpha ketoacids
pyruvate dehydrogenase
pyruvate acetyl CoA
alphaketoglutarate dehydrogease
alpha keto glutarate succinyl CoA
2.Lipid metabolism :
acyl CoA dehydrogenase
acyl Co A alpha ,beta unsaturated acyl CoA
3. Protein metabolism :
D-aminoacid oxidase
D-aminoacid alpha ketoacid + NH3
4. Purine catabolism:
xanthine oxidase
Xanthine uric aicd

FMN dependent reactions:
a) Aminoacid oxidation FMN reduced to FMNH2

L- aminoacid oxidase
L-Aminoacid alpha keto acid + NH3

FMN FMNH2

H2O2 O2
catalase
H2O + O2
b) Electron transport chain : NADH dehydrogenase contains FMN
.
e- e-
NAD FMN CoQ
Deficiency :
Causes usually associated with other deficiencies such as B1,
niacin , protein
Phototherapy for neonatal jaundice causes TRANSIENT
deficiency.
Manifestations:
Cheilosis
Glossitis
Angular stomatitis
Magenta coloured tongue painful glossitis
Seborrhoeic dermatitis

Coenzyme forms
The coenzyme forms of riboflavina re flavin mononucleotide (FMN)
and flavin adenine dinuceotide (FAD)
Riboflavin is converted to FMN in a reaction catalyzed by
flavokinase.
FMN is converted to FAD by the addition of AMP.
The reaction is catalyzed by FAD pyrophosphorylase.
Flavin coenzymes function as electron carriers for
oxidationreduction reactions
Reactions requiring FMN
NADH dehydrogenase
Catalyzes the transfer of electrons from NADH coenzyme.

In this reaction, FMN is involved in the transfer of electrons from
NADH to iron sulfur proteins.

Electrons are then transferred to coenzyme Q.
L-amino acid oxidase

Catalyzes the conversion of L-amino acid to the ketoacid.
Ammonia is released.

FMN is reduced to FMNH
2
during the reaction.
Reactions requiring FAD
-ketoglutarate dehydrogenase complex
Catalyzes the oxidative decarboxylation of -ketoglutarate to
succnyl CoA.
The dihydrolipoyl dehydrogenase component of -ketoglutarate
dehydrogenase complex contains FAD.
This reaction is one of the reactions of citric acid cycle.
Acyl CoA dehydrogenase
catalyzes the oxidation of fatty acyl CoA to 2,3 unsaturated acyl
Coa.
This reaction occurs during oxidation of fatty acids.
Mitochondrial glycerol 3-phosphate dehydrogenase
catalyzes the conversion of glycerol 3-phosphate to
dihydroxyacetone phosphate in the mitochondria.
The reaction is essential for carrying reducing equivalents (NAD)
from cytosol to the mitochondria.

Xanthine oxidase
Catalyzes the oxidation hypoxanthine to xanthine and xanthine
to uric acid.
Xanthine oxidase contains FAD , molybdenum and iron.
Glycine cleavage system
Catalyzes the conversion of glycine to CO
2
and ammo0nia.
During the reaction, FH
4
is converted to N
510
methylene FH
4

D-Amino oxidase
Catalyzes the conversion of D-amino acids or glycine (absence
of asymmetric carbon atom) to corresponding keto acids.
Ammonis is released and FAD is reduced to FADH
2

Succinate dehydrogenase

Catalyzes the oxidation of succinate fumarate.
FAD is reduced to FADH
2.






This reaction is a reaction of citric acid cycle.
Pyruvate dehydrogenase complex
Catalyzes the oxidative decarboxylation of pyruvate to acetyl CoA.

In this reaction, NAD is reduced to NADH+H
+.

The dihydrolipoyl dehydrogenase component of pyruvate dehydrogenase
complex contains FAD.
Glutathione reductase

Catalyzes the reduction of oxidized glutathione to reduced
glutathione.

NADPH for the reaction is derived from pentose phosphate pathway.