Water Soluble vitamins

1
VITAMINS

• M.Prasad Naidu
• MSc Medical Biochemistry, Ph.D,.

2

• 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

3

• 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

4

• Water Soluble vitamins

5
THIAMINE (B1)

• Sulphur containing vitamin
• Synonyms
• Anti-beriberi factor , anti-neuritic vitamin,
  aneurin.

6
SOURCES

• PLANT SOURCES
• Rich source- ALEURONE LAYER of cereals .
• Good sources unpolished rice ,
• whole wheat, peas,beans
• ANIMAL SOURCES
• Liver , meat , eggs

7

• 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.

8
Coenzyme form Thiamine pyrophosphate (TPP)

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

9

• BIOCHEMICAL FUNCTIONS
• A .Involved in carbohydrate metabolism.
• Pyruvate dehydrogenase oxidative
  decarboxylation of pyruvate.
• CoA.SH PDH CO2
• Pyruvate
  acetylCoA
• NAD TPP NADH
  H

10
2. a-ketoglutarate dehydrogenase
Oxidativedecarboxylation of alpha ketoglutarate
in TCA cycle CoA.SH
CO2 ?lpha-ketogluatarate
Succinyl co A
NAD TPP
NADH H
11
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
12
C . Transketolase Reaction of HMP Shunt
13

• D. Nerve transmission
• TPP is required for Acetylcholine synthesis and
  in ion translocation of neural tissue.
• Pyruvate acetyl CoA
• acetyl choline

14
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
15

• 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.

16
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 .
17

• 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.

18

• 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.

19

• 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.

20

• 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.

21
THIAMINE
22
(No Transcript)
23

• 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

24
(No Transcript)
25

• ?-ketoglutarate dehydrogenase complex
• catalyzes the conversion of a-ketoglutarate to
  succinyl CoA.
• The reaction occurs in citric acid cycle.

26

• a-keto acid (branched chain) dehydrogenase
  complex
• catalyzes the conversion of a-keto acids derived
  from branched chain amino acid to form
  corresponding acyl CoAs.
• this is a reaction of catabolism of branched
  chain amino acids.

27

• Transketolase
• Catalyzes two reactions of pentose phosphate
  pathway

28
(No Transcript)
29
(No Transcript)
30

• 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

31
(No Transcript)
32

• 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

33

• 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

34

• Late symptoms Neurological
• Ataxia
• Mental confusion
• Loss of eye coordination
• Prolonged deficiency leads to Cardiovascular and
  muscular defects

35
Riboflavin (B2)
36

• 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

37
Coenzyme forms

• Flavin mononucleotide (FMN)
• Flavin adenine dinucleotide (FAD)
• flavokinase FAD synthase
• Riboflavin FMN FAD
• ATP ADP ATP
  PPi

38

• Biochemical functions
• FAD dependent reactions
• Carbohydrate metabolism
• a) Tricarboxylic cycle (TCA)
• succinate
  dehydrogenase
• succinate FAD
  fumarateFADH2
• b)oxidative decarboxylation of alpha
  ketoacids
• pyruvate
  dehydrogenase
• pyruvate
  acetyl CoA
• 
  alphaketoglutarate dehydrogease
• alpha keto glutarate
  succinyl CoA

39
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
40

• FMN dependent reactions
• Aminoacid oxidation FMN reduced to FMNH2
• L- aminoacid oxidase
• L-Aminoacid alpha
  keto acid NH3
• FMN FMNH2
• H2O2 O2
• catalase
• H2O ½ O2
• Electron transport chain NADH dehydrogenase
  contains FMN .
• e- e-
• NAD FMN CoQ

41

• 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

42
(No Transcript)
43

• 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

44

• 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.

45

• L-amino acid oxidase
• Catalyzes the conversion of L-amino acid to the
  aketoacid.
• Ammonia is released.
• FMN is reduced to FMNH2 during the reaction.

46

• Reactions requiring FAD
• a-ketoglutarate dehydrogenase complex
• Catalyzes the oxidative decarboxylation of
  a-ketoglutarate to succnyl CoA.
• The dihydrolipoyl dehydrogenase component of
  a-ketoglutarate dehydrogenase complex contains
  FAD.
• This reaction is one of the reactions of citric
  acid cycle.

47

• Acyl CoA dehydrogenase
• catalyzes the oxidation of fatty acyl CoA to 2,3
  unsaturated acyl Coa.
• This reaction occurs during ß oxidation of fatty
  acids.

48

• 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.

49

• Xanthine oxidase
• Catalyzes the oxidation hypoxanthine to xanthine
  and xanthine to uric acid.
• Xanthine oxidase contains FAD , molybdenum and
  iron.

50

• Glycine cleavage system
• Catalyzes the conversion of glycine to CO2 and
  ammo0nia.
• During the reaction, FH4 is converted to N510
  methylene FH4

51

• 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 FADH2

52

• Succinate dehydrogenase
• Catalyzes the oxidation of succinate fumarate.
• FAD is reduced to FADH2.
• This reaction is a reaction of citric acid cycle.

53

• Pyruvate dehydrogenase complex
• Catalyzes the oxidative decarboxylation of
  pyruvate to acetyl CoA.
• In this reaction, NAD is reduced to NADHH.
• The dihydrolipoyl dehydrogenase component of
  pyruvate dehydrogenase complex contains FAD.

54

• Glutathione reductase
• Catalyzes the reduction of oxidized glutathione
  to reduced glutathione.
• NADPH for the reaction is derived from pentose
  phosphate pathway.

55
THANK YOU