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VITAMINSM.Prasad NaiduMSc Medical Biochemistry, Ph.D,.
Objectives:Definition of VitaminsClassification of Vitamins
1. water soluble 2. Fat soluble
Diferenses between water soluble vitamins & Fat soluble vitaminsVitamin like compoundsProvitaminsAntivitaminsHypervitaminosis
When we speak and write individual vitamins under the following headings.
ChemistrySourcesRDACo-enzyme or active formBiochemical functionsCauses of deficiencyDeficiency manifestationsAssay
Water Soluble vitamins
THIAMINE (B1)
Sulphur containing vitamin
Synonyms: Anti-beriberi factor , anti-neuritic
vitamin, aneurin.
SOURCESPLANT 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/ dayRequirement increased inOld age, pregnancy ,lactation and
alcoholism.
Coenzyme form :Thiamine pyrophosphate (TPP)
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 CO2Pyruvate acetylCoA NAD+ TPP NADH + H+
2. α-ketoglutarate dehydrogenase – Oxidativedecarboxylation of alpha ketoglutarate in TCA cycle CoA.SH CO2
Αlpha-ketogluatarate Succinyl co A
NAD+ TPP NADH + H+
B. OXIDATIVE DECARBOXYLATION OF BRANCHED CHAIN AMINOACIDSBranched chain aminoacids (leucine, isoleucine ,valine)
Corresponding alpha keto acids NAD+, CoASH TPP alpha keto acid dehydrogenaseNADH +H+, CO2Corressponding alpha,beta unsaturated acyl CoA
C . Transketolase Reaction of HMP Shunt
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-BERIEarly 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 promoteextravasation 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 cardiacenlargement. This is further increased, because the overworked tissue cannot use glucose efficiently as an energy substrate.
WERNICKE KORSAKOFF’s 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
Α-ketoglutarate dehydrogenase complex
catalyzes the conversion of α-ketoglutarate to succinyl CoA.The reaction occurs in citric acid cycle.
α-keto acid (branched chain) dehydrogenase complexcatalyzes the conversion of α-keto acids derived from branched chain amino acid to form corresponding acyl CoAs.
this is a reaction of catabolism of branched chain amino acids.
TransketolaseCatalyzes two reactions of pentose phosphate pathway
Biochemical functions:
Mainly carbohydrate metabolismT.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 manifestationsBeri Beri:More vulnerable – who take high
polished rice chronic alcoholics – no proper food is taken.
pregnancy, lactation – more required.
Early symptoms ConstipationAnorexiaMental depriesionPeripheral
neuropathyFatigue
Late symptoms Neurological Ataxia Mental confusion Loss of eye
coordinationProlonged 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
Coenzyme forms Flavin mononucleotide (FMN)Flavin adenine dinucleotide
(FAD)
flavokinase FAD synthaseRiboflavin 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 CoA3. Protein metabolism : D-aminoacid oxidase D-aminoacid alpha ketoacid + NH34. 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 + ½ 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 formsThe 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 FMNNADH dehydrogenaseCatalyzes 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 αketoacid.
Ammonia is released.
FMN is reduced to FMNH2 during the reaction.
Reactions requiring FADα-ketoglutarate dehydrogenase complexCatalyzes the oxidative decarboxylation of α-
ketoglutarate to succnyl CoA.The dihydrolipoyl dehydrogenase component of α-
ketoglutarate dehydrogenase complex contains FAD.This reaction is one of the reactions of citric acid cycle.
Acyl CoA dehydrogenasecatalyzes the oxidation of fatty acyl CoA to 2,3 unsaturated acyl Coa.
This reaction occurs during β oxidation of fatty acids.
Mitochondrial glycerol 3-phosphate dehydrogenasecatalyzes 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 oxidaseCatalyzes the oxidation hypoxanthine to xanthine
and xanthine to uric acid.Xanthine oxidase contains FAD , molybdenum and
iron.
Glycine cleavage systemCatalyzes the conversion of glycine to CO2 and
ammo0nia. During the reaction, FH4 is converted to N510
methylene FH4
D-Amino oxidaseCatalyzes 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 FADH2
Succinate dehydrogenase
Catalyzes the oxidation of succinate fumarate.FAD is reduced to FADH2.
This reaction is a reaction of citric acid cycle.
Pyruvate dehydrogenase complexCatalyzes 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.
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