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Biochemistry For Medics
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1Biochemistry for medics- Namrata Chhabra
2Biochemistry for medics- Namrata Chhabra
 Introduction to Vitamin B6
 Structure of Vitamin B6
 Activation of Vitamin B6
 Role in Amino Acid Metabolism
Overview of Seminar
 General Amino Acid Reactions
 Metabolism of Tryptophan
 Metabolism of Methionine
 Metabolism of Glycine
3Biochemistry for medics- Namrata Chhabra
 Introduction to Vitamin B6
 Structure of Vitamin B6
 Activation of Vitamin B6
 Role in Amino Acid Metabolism
Overview of Seminar
 General Amino Acid Reactions
 Metabolism of Tryptophan
 Metabolism of Methionine
 Metabolism of Glycine
4Biochemistry for medics- Namrata Chhabra
B-Complex Vitamins
 Water Soluble Vitamins
 Earlier thought of as being a Single Vitamin
 Later found to be composed of EIGHT Chemically distinct Vitamins
Vitamin B1 (Thiamine)
Vitamin B2 (Riboflavin)
Vitamin B3 (Niacin)
Vitamin B5
(Pantothenic Acid)
Vitamin B6
Vitamin B7 (Biotin)
Vitamin B9 (Folic Acid)
Vitamin B12
(Cobalamin)
INTRODUCTIO
N:
5Biochemistry for medics- Namrata Chhabra
B-Complex Vitamins
 Water Soluble Vitamins
 Earlier thought of as being a Single Vitamin
 Later found to be composed of EIGHT Chemically distinct Vitamins
Vitamin B1 (Thiamine)
Vitamin B2 (Riboflavin)
Vitamin B3 (Niacin)
Vitamin B5
(Pantothenic Acid)
Vitamin B6
Vitamin B7 (Biotin)
Vitamin B9 (Folic Acid)
Vitamin B12
(Cobalamin)
Vitamin B6
INTRODUCTIO
N:
6Biochemistry for medics- Namrata Chhabra
B-Complex Vitamins
INTRODUCTIO
N:  Water Soluble Vitamins
 Earlier thought of as being a Single Vitamin
 Later found to be composed of EIGHT Chemically distinct Vitamins
Vitamin B1 (Thiamine)
Vitamin B2 (Riboflavin)
Vitamin B3 (Niacin)
Vitamin B5
(Pantothenic Acid)
Vitamin B6
Vitamin B7 (Biotin)
Vitamin B9 (Folic Acid)
Vitamin B12
(Cobalamin)
Vitamin B6
7Biochemistry for medics- Namrata Chhabra
HISTOR
Y:
Introduction
 Discovered in 1934
 Hungarian physician, Paul György
 Ability to cure Dermititis Acrodynia in Rats
 Isolated in 1938
 Polish nutritionist, Samuel Lepkovsky
 Isolated from Rice Bran
 Structure of Pyridoxine in 1939
 Harris and Folkers
 Structure of Pyridoxal and Pyridoxamine in 1945
 American Biochemist, Esmond Snell
8Biochemistry for medics- Namrata Chhabra
GOOD
SOURCES
Sources of Vitamin B6
 Vitamin B6 is ABUNDANTLY present in:
 Royal Jelly of Bees
 Yeast
 Rice Polishing
 Cereal Grains
 Egg Yolk
 Germinal portion of various Seeds
MODERATE
SOURCES
 Vitamin B6 is MODERATELY present in:
 Liver
 Kidney
 Muscle
 Fish
POOR
SOURCES
 Vitamin B6 is POORLY present in:
 Milk
9Biochemistry for medics- Namrata Chhabra
Structure
 Derivatives of Pyridine Ring
Pyridine Ring
10Biochemistry for medics- Namrata Chhabra
Structure
 Derivatives of Pyridine Ring
Purine RingPyridoxine
2-Methly, 3-Hydroxy, 4,5-diHydroxyMethly Pyridine
 Pyridoxine
11Biochemistry for medics- Namrata Chhabra
Structure
 Pyridoxal
Purine RingPyridoxal
12Biochemistry for medics- Namrata Chhabra
Structure
 Pyridoxamine
Purine RingPyridoxamine
13Biochemistry for medics- Namrata Chhabra
Structure
 Derivatives of Pyridine
 Pyridoxine
 Also known as Pyridoxol
 4th position contains a CH2OH group
 Precursor from of Vitamin B6
 Plant in origin Pyridoxine
Pyridoxal
Pyridoxamine
 Pyridoxal
 4th position contains a CHO group
 Precursor from of Vitamin B6
 Plant in origin
 Pyridoxamine
 4th position contains a CH2NH2 group
 Precursor from of Vitamin B6
 Plant in origin
14Biochemistry for medics- Namrata Chhabra
Structure
 Biochemically active only when Phosphorylated
 Phosphorylation is brought about by Kinase enzyme
 Phosphorylation occurs at 5th Position
Pyridoxine Pyridoxine-P (Phosphate)
Kinase
15Biochemistry for medics- Namrata Chhabra
Structure
 Pyridoxine
 Also known as Pyridoxol
 4th position contains a CH2OH group
 Precursor from of Vitamin B6
 Plant in origin
 Pyridoxal
 4th position contains a CHO group
 Precursor from of Vitamin B6
 Plant in origin
 Pyridoxamine
 4th position contains a CH2NH2 group
 Precursor from of Vitamin B6
 Plant in origin
Pyridoxine
Pyridoxal
Pyridoxamine
16Biochemistry for medics- Namrata Chhabra
Structure
Pyridoxine
Pyridoxal
Pyridoxamine
Pyridoxine-P
Pyridoxal-P
Pyridoxamine-P
Kinase
Kinase
Kinase
17Biochemistry for medics- Namrata Chhabra
Structure
 Biochemically active only when Phosphorylated
 Phosphorylation is brought about by Kinase enzyme
 Phosphorylation occurs at 5th Position
 In total, there are 6 isoforms of Vitamin B6:
Pyridoxine Pyridoxine-P (Phosphate)
 Pyridoxine
 Pyridoxine-P
 Pyridoxal
 Pyridoxal-P
 Pyridoxamine
 Pyridoxamine-P
18Biochemistry for medics- Namrata Chhabra
Structure
 Biochemically active only when Phosphorylated
 Phosphorylation is brought about by Kinase enzyme
 Phosphorylation occurs at 5th Position
 In total, there are 6 isoforms of Vitamin B6:
 Pyridoxine
 Pyridoxine-P
 Pyridoxal
 Pyridoxal-P
 Pyridoxamine
 Pyridoxamine-P
 Pyridoxic Acid
 Excretory form of Vitamin B6
 Oxidation at 4th position
Pyridoxic Acid
NOTE: Vitamin B6 can also be excreted
in the UNCHARGED form as Pyridoxine or
Pyridoxal
19Biochemistry for medics- Namrata Chhabra
Structure
 Biochemically active only when Phosphorylated
 Phosphorylation is brought about by Kinase enzyme
 Phosphorylation occurs at 5th Position
 In total, there are 6 isoforms of Vitamin B6:
 Pyridoxine
 Pyridoxine-P
 Pyridoxal
 Pyridoxal-P
 Pyridoxamine
 Pyridoxamine-P
 Pyridoxic Acid
 Excretory form of Vitamin B6
 Oxidation at 4th position
Pyridoxic Acid
NOTE: Vitamin B6 can also be excreted
in the UNCHARGED form as Pyridoxine or
Pyridoxal
20Biochemistry for medics- Namrata Chhabra
Activation of Vitamin B6
 Biologically active forms are: a) Pyridoxal-PO4
b) Pyridoxamine-PO4
Pyridoxine Pyridoxal
Pyridoxal-P
Dehydrogenase
Pyridoxal Kinase
H2
ATP
ADP
Zn2+
Mg2+
21Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Absorption is by either PASSIVE or ACTIVE mechanisms
 Vitamin B6 is absorbed by ACTIVE TRANSPORT
 Amino Acid Absorption
22Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Transamination Reactions
 SGPT (Serum Glutamate Pyruvate Transaminase)
Glutamate Pyruvate
23Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Transamination Reactions
 SGPT (Serum Glutamate Pyruvate Transaminase)
Glutamate Pyruvate
24Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Transamination Reactions
 SGPT (Serum Glutamate Pyruvate Transaminase)
Glutamate PyruvateAlanine α-keto Glutarate
25Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
Pyridoxal-P
Pyruvic Acid
(Recipient α-keto acid)
Glutamate
(Donor α-amino acid)
Mechanism of Reaction
26Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
Pyridoxal-P
Pyruvic Acid
(Recipient α-keto acid)
Glutamate
(Donor α-amino acid)
Mechanism of Reaction
27Biochemistry for medics- Namrata Chhabra
Pyridoxal-P
Glutamate
(Donor α-amino acid)
Role in Amino Acid Metabolism
Pyridoxal-P
Pyruvic Acid
(Recipient α-keto acid)
Glutamate
(Donor α-amino acid)
α-keto Glutarate
(New α-keto acid) Pyridoxamine-P
Mechanism of Reaction
28Biochemistry for medics- Namrata Chhabra
Pyruvic Acid
(Recipient α-keto acid)
Role in Amino Acid Metabolism
Pyridoxal-P
Pyruvic Acid
(Recipient α-keto acid)
Glutamate
(Donor α-amino acid)
α-keto Glutarate
(New α-keto acid) Pyridoxamine-P
Alanine
(New α-amino acid)
Pyridoxal-P
Mechanism of Reaction
29Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Transamination Reactions
 SGPT (Serum Glutamate Pyruvate Transaminase)
α-keto Glutarate
(New α-keto acid)
Alanine
(New α-amino acid)
Pyruvate
(Recipient α-keto acid)
Glutamate
(Donor α-amino acid)
SGPT
B6-P
+ +
30Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Transamination Reactions
 SGPT (Serum Glutamate Pyruvate Transaminase)
α-keto Glutarate
(New α-keto acid)
Alanine
(New α-amino acid)
Pyruvate
(Recipient α-keto acid)
Glutamate
(Donor α-amino acid)
SGPT
B6-P
+ +
31Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Transamination Reactions
 SGPT (Serum Glutamate Pyruvate Transaminase)
Pyruvate + Glutamate Alanine + α-keto Glutarate
 SGOT (Serum Glutamate Oxaloacetate Transaminase)
Oxaloacetate + Glutamate Aspartate + α-keto Glutarate
CLINICAL SIGNIFICANCE
 Synthesis of Non-Essential Amino Acids
 Alanine
 Aspartate
 Recycling of Carbon Skeletons
 Pyruvate
 Oxaloacetate
32Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Transamination Reactions
 SGPT (Serum Glutamate Pyruvate Transaminase)
Pyruvate + Glutamate Alanine + α-keto Glutarate
 SGOT (Serum Glutamate Oxaloacetate Transaminase)
Oxaloacetate + Glutamate Aspartate + α-keto Glutarate
CLINICAL SIGNIFICANCE
 Synthesis of Non-Essential Amino Acids
 Alanine
 Aspartate
 Recycling of Carbon Skeletons
 Pyruvate
 Oxaloacetate
33Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Deamination Reactions
 Non-Oxidative Deamination
Serine
34Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Deamination Reactions
 Non-Oxidative Deamination
Dehydrase
H2O
B6-P
H2ONH3
Serine Imino Acid
Pyruvate
Imino Acid
35Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Deamination Reactions
 Non-Oxidative Deamination
Dehydrase
H2O
B6-P
H2ONH3
Serine Imino Acid
Pyruvate
Imino Acid
36Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Deamination Reactions
 Non-Oxidative Deamination
 Serine Deamination
 Cysteine Deamination
Serine
Cysteine
Pyruvate
Pyruvate
Water
Hydrogen Sulphide
+
+
Dehydrase
B6-P
Desulfhydrase
B6-P
CLINICAL SIGNIFICANCE  Breakdown of excess amino acids in Liver
 Contributes to NH3 formation in the body
NH3
NH3
37Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Deamination Reactions
 Non-Oxidative Deamination
 Serine Deamination
 Cysteine Deamination
Serine
Cysteine
Pyruvate
Pyruvate
Water
Hydrogen Sulphide
+
+
Dehydrase
B6-P
Desulfhydrase
B6-P
CLINICAL SIGNIFICANCE  Breakdown of excess amino acids in Liver
 Contributes to NH3 formation in the body
NH3
NH3
38Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Interconversion of Amino Acids
 Racemases
 Conversion of L-amino Acids to D-Amino Acids
 Conversion of D-Amino Acids to L-Amino Acids
RACEMASE
B6-P
L-AlanineD-Alanine
39Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Interconversion of Amino Acids
 Racemase
 Conversion of L-amino Acids to D-Amino Acids
 Conversion of D-Amino Acids to L-Amino Acids
RACEMASE
B6-P
L-AlanineD-Alanine
40Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Decarboxylation Reactions
 Removal of CO2 to produce AMINES
Histidine
41Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Decarboxylation Reactions
 Removal of CO2 to produce AMINES
Decarboxylase
B6-P
CO2
Histidine
42Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Decarboxylation Reactions
 Removal of CO2 to produce AMINES
Decarboxylase
B6-P
CO2
HistamineHistidine
43Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Decarboxylation Reactions
 Removal of CO2 to produce AMINES
Decarboxylase
B6-P
CO2
HistamineHistidine
44Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 General Amino Acid Reactions
Decarboxylation Reactions
 Removal of CO2 to produce AMINES
Histidine
5-OH Tryptophan
Glutamic Acid
Histamine
5-OH Tryptamine (Serotonin)
γ-Amino Butyric Acid
Decarboxylase
B6-P
CO2
Decarboxylase
B6-P
CO2
Decarboxylase
B6-P
CO2
45Biochemistry for medics- Namrata Chhabra
 Histamine
 Synthesised by Basophils and Mast Cells
 Mediator of Hypersensitivity Reactions
 Triggers Inflammatory Reactions
 Neurotransmitter in the Gut
 γ-Amino Butyric Acid
 Inhibitor Neurotransmitter in the CNS
 GABA Deficiency produces a state of Hyper excitation
 Convulsions
 Precipitating factor for Epileptic Seizures
 Serotonin
 Neurotransmitter in CNS
 Regulates Behaviour and Cognitive functions
 Deficiency leads to Depression, Anxiety and Personality Disorders
 Regulates Intestinal Motility in Gut
Role in Amino Acid Metabolism
CLINICAL SIGNIFICANCE
46Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Tryptophan Metabolism
Tryptophan
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
NIACIN
Kynureninase
B6-P
47Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Tryptophan Metabolism
Tryptophan
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
NIACIN
Kynureninase
B6-P
CLINICAL SIGNIFICANCE
 Pathway for Endogenous NIACIN synthesis
 In Vitamin B6 deficiency
 Niacin Deficiency
 PELLAGRA sets in
† Dermatitis
48Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Tryptophan Metabolism
Tryptophan
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
NIACIN
Kynureninase
B6-P
CLINICAL SIGNIFICANCE
 Pathway for Endogenous NIACIN synthesis
 In Vitamin B6 deficiency
 Niacin Deficiency
 PELLAGRA sets in
† Dermatitis
49Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Tryptophan Metabolism
Tryptophan
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
NIACIN
Kynureninase
B6-P
CLINICAL SIGNIFICANCE
 Pathway for Endogenous NIACIN synthesis
 In Vitamin B6 deficiency
 Niacin Deficiency
 PELLAGRA sets in
† Dermatitis
† Dementia
50Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Tryptophan Metabolism
Tryptophan
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
NIACIN
Kynureninase
B6-P
CLINICAL SIGNIFICANCE
 Pathway for Endogenous NIACIN synthesis
 In Vitamin B6 deficiency
 Niacin Deficiency
 PELLAGRA sets in
† Dermatitis
† Dementia
† Diarrhoea
51Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Tryptophan Metabolism
Tryptophan
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
NIACIN
Kynureninase
B6-P
CLINICAL SIGNIFICANCE
 Pathway for Endogenous NIACIN synthesis
 In Vitamin B6 deficiency
 Niacin Deficiency
 PELLAGRA sets in
† Dermatitis
† Dementia
† Diarrhoea
† DEATH
52Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Tryptophan Metabolism
Tryptophan
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
NIACIN
Kynureninase
B6-P
CLINICAL SIGNIFICANCE
 Pathway for Endogenous NIACIN synthesis
 In Vitamin B6 deficiency
 Niacin Deficiency
 PELLAGRA sets in
† Dermatitis
† Dementia
† Diarrhoea
† DEATH
 In ISONIAZID therapy for Tuberculosis
Isoniazid
+
Isoniazid B6-P Hydrasone
B6-P
53Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Tryptophan Metabolism
Tryptophan
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
NIACIN
Kynureninase
B6-P
CLINICAL SIGNIFICANCE
 Pathway for Endogenous NIACIN synthesis
 In Vitamin B6 deficiency
 Niacin Deficiency
 PELLAGRA sets in
† Dermatitis
† Dementia
† Diarrhoea
† DEATH
 In ISONIAZID therapy for Tuberculosis
Isoniazid
+
Isoniazid B6-P Hydrasone
B6-P
B6-P
54Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Tryptophan Metabolism
Tryptophan
NIACIN
CLINICAL SIGNIFICANCE
 Pathway for Endogenous NIACIN synthesis
 In Vitamin B6 deficiency
 In ISONIAZID therapy for Tuberculosis
 Tryptophan Loading Test
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
Kynureninase
B6-P
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
Kynureninase
B6-P
55Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Tryptophan Metabolism
Tryptophan
NIACIN
CLINICAL SIGNIFICANCE
 Pathway for Endogenous NIACIN synthesis
 In Vitamin B6 deficiency
 In ISONIAZID therapy for Tuberculosis
 Tryptophan Loading Test
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
Kynureninase
B6-P
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
Kynureninase
B6-P
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
Kynureninase
B6-P
Xanthurenic Acid
56Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Tryptophan Metabolism
Tryptophan
NIACIN
CLINICAL SIGNIFICANCE
 Pathway for Endogenous NIACIN synthesis
 In Vitamin B6 deficiency
 In ISONIAZID therapy for Tuberculosis
 Tryptophan Loading Test
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
Kynureninase
B6-P
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
Kynureninase
B6-P
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
Kynureninase
B6-P
Xanthurenic Acid
57Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Methionine Metabolism
 Methionine metabolism occurs in 2 phases
 Phase I - Conversion of Methionine to HOMOCYSTEINE
 Phase II - Further metabolism of HOMOCYSTEINE
Methionine
HOMOCYSTEINE Serine+
Cystathionine
CysteineHomoserine
Cystathionine β SynthaseB6-P
Cystathionine LyaseB6-P
CLINICAL SIGNIFICANCE
 Pathway for synthesis of Non-Essential
Amino Acids like Cysteine
 In Vitamin B6 deficiency
 HOMOCYSTEINAEMIA
 Homocysteine is Atherogenic
 Ischaemic Heart Disease
 Brain Stroke
58Biochemistry for medics- Namrata Chhabra
Role in Amino Acid Metabolism
 Glycine Metabolism
Glycine
HydroxyMethly THF
Interconversion of Glycine to Serine
59Biochemistry for medics- Namrata Chhabra
Serine Hydroxymethly
Transferase
B6-P
Glycine
Serine
“Free” THF
HydroxyMethly THF
Role in Amino Acid Metabolism
 Glycine Metabolism
Interconversion of Glycine to Serine
CLINICAL SIGNIFICANCE
 Synthesis of Non-Essential
Amino Acid Serine
60Biochemistry for medics- Namrata Chhabra
Serine Hydroxymethly
Transferase
B6-P
Glycine
Serine
“Free” THF
HydroxyMethly THF
Role in Amino Acid Metabolism
 Glycine Metabolism
Interconversion of Glycine to Serine
CLINICAL SIGNIFICANCE
 Synthesis of Non-Essential
Amino Acid Serine
61Biochemistry for medics- Namrata Chhabra
Tetra Hydro Folate
B6-P
GCS
Glycine
Role in Amino Acid Metabolism
 Glycine Metabolism
Glycine Cleavage System
62Biochemistry for medics- Namrata Chhabra
Tetra Hydro Folate
+
N5,10 Methylene Tetra Hydro Folate
B6-P
GCS
Glycine
Role in Amino Acid Metabolism
 Glycine Metabolism
Glycine Cleavage System
Carbon Dioxide Ammonia
63Biochemistry for medics- Namrata Chhabra
+
B6-P
GCS
Glycine
Role in Amino Acid Metabolism
 Glycine Metabolism
Glycine Cleavage System
CLINICAL SIGNIFICANCE
dUMP dTMP
Di Hydro Folate
DNA Synthesis
N5,10 Methylene Tetra Hydro Folate
Thymidylate Synthase
Carbon Dioxide Ammonia
64Biochemistry for medics- Namrata Chhabra
+
B6-P
GCS
Glycine
Role in Amino Acid Metabolism
 Glycine Metabolism
Glycine Cleavage System
CLINICAL SIGNIFICANCE
dUMP dTMP
Di Hydro Folate
DNA Synthesis
Thymidylate Synthase
Carbon Dioxide Ammonia
N5,10 Methylene Tetra Hydro Folate
65Biochemistry for medics- Namrata Chhabra
GlycineAcetyl CoA
+
Role in Amino Acid Metabolism
 Glycine Metabolism
Synthesis of Amino Acetone
66Biochemistry for medics- Namrata Chhabra
GlycineAcetyl CoA
Amino Acetone
Synthetase
B6-P
+
Role in Amino Acid Metabolism
 Glycine Metabolism
Synthesis of Amino Acetone
67Biochemistry for medics- Namrata Chhabra
Amino Acetone
GlycineAcetyl CoA
Amino Acetone
Synthetase
B6-P
+
Role in Amino Acid Metabolism
 Glycine Metabolism
Synthesis of Amino Acetone
CLINICAL SIGNIFICANCE
 Amino Acetone has a role in
Metabolism†
† Elliott, W.H., et al., 1959. Amino Acteone: Its
Isolation and Role in Metabolism, Canberra.
Nature: 183, 1051-1052.
68Biochemistry for medics- Namrata Chhabra
 Sources of Vitamin B6
 Structure of Vitamin B6
 Activation of Vitamin B6
 Role in Amino Acid Metabolism
 General Amino Acid Reactions
 Metabolism of Tryptophan
 Metabolism of Methionine
 Metabolism of Glycine
SUMMARY
69Biochemistry for medics- Namrata Chhabra
 Biehl, J.P., et al., 1954. Effect of Isoniazid on Vitamin B6 Metabolism; Its
Possible Significance in Producing Isoniazid Neuritis, London. Royal
Society of Medicine Press; 85:389-392.
 Robinson, K., et al., 1996. Hyperhomocysteinemia Confers an Independent
Increased Risk of Atherosclerosis in End-Stage Renal Disease and Is Closely
Linked to Plasma Folate and Pyridoxine Concentrations, Boston.
Circulation; 94:2743-2748
Bibliography
 Chatterjea, M.N., Shinde, R., 2008. Textbook of Medical Biochemistry, 7th
Edition, New Delhi. Jaypee.
 Murray, R.K., et al., 2009. Harper’s Illustrated Biochemistry, 28th Edition, New
York. McGraw Hill.
 Champe, C., et al., 2008. Lippincott’s Illustrated Review of Biochemistry, 4th
Edition , New York. Lippincott Williams and Wilkins.
 Chabba, N., 2011. Vitamin B6 chemistry, Activation and Role in Amino Acid
Metabolism. Biochemistry Lecture, Mauritius, SSR Medical College.
UNPUBLISHED.
70Biochemistry for medics- Namrata Chhabra
71Biochemistry for medics- Namrata Chhabra

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  • 1. Biochemistry For Medics www.namrata.co Accepted for publication in Biochemistry for medics In Student’s corner 1Biochemistry for medics- Namrata Chhabra
  • 2. 2Biochemistry for medics- Namrata Chhabra
  • 3.  Introduction to Vitamin B6  Structure of Vitamin B6  Activation of Vitamin B6  Role in Amino Acid Metabolism Overview of Seminar  General Amino Acid Reactions  Metabolism of Tryptophan  Metabolism of Methionine  Metabolism of Glycine 3Biochemistry for medics- Namrata Chhabra
  • 4.  Introduction to Vitamin B6  Structure of Vitamin B6  Activation of Vitamin B6  Role in Amino Acid Metabolism Overview of Seminar  General Amino Acid Reactions  Metabolism of Tryptophan  Metabolism of Methionine  Metabolism of Glycine 4Biochemistry for medics- Namrata Chhabra
  • 5. B-Complex Vitamins  Water Soluble Vitamins  Earlier thought of as being a Single Vitamin  Later found to be composed of EIGHT Chemically distinct Vitamins Vitamin B1 (Thiamine) Vitamin B2 (Riboflavin) Vitamin B3 (Niacin) Vitamin B5 (Pantothenic Acid) Vitamin B6 Vitamin B7 (Biotin) Vitamin B9 (Folic Acid) Vitamin B12 (Cobalamin) INTRODUCTIO N: 5Biochemistry for medics- Namrata Chhabra
  • 6. B-Complex Vitamins  Water Soluble Vitamins  Earlier thought of as being a Single Vitamin  Later found to be composed of EIGHT Chemically distinct Vitamins Vitamin B1 (Thiamine) Vitamin B2 (Riboflavin) Vitamin B3 (Niacin) Vitamin B5 (Pantothenic Acid) Vitamin B6 Vitamin B7 (Biotin) Vitamin B9 (Folic Acid) Vitamin B12 (Cobalamin) Vitamin B6 INTRODUCTIO N: 6Biochemistry for medics- Namrata Chhabra
  • 7. B-Complex Vitamins INTRODUCTIO N:  Water Soluble Vitamins  Earlier thought of as being a Single Vitamin  Later found to be composed of EIGHT Chemically distinct Vitamins Vitamin B1 (Thiamine) Vitamin B2 (Riboflavin) Vitamin B3 (Niacin) Vitamin B5 (Pantothenic Acid) Vitamin B6 Vitamin B7 (Biotin) Vitamin B9 (Folic Acid) Vitamin B12 (Cobalamin) Vitamin B6 7Biochemistry for medics- Namrata Chhabra
  • 8. HISTOR Y: Introduction  Discovered in 1934  Hungarian physician, Paul György  Ability to cure Dermititis Acrodynia in Rats  Isolated in 1938  Polish nutritionist, Samuel Lepkovsky  Isolated from Rice Bran  Structure of Pyridoxine in 1939  Harris and Folkers  Structure of Pyridoxal and Pyridoxamine in 1945  American Biochemist, Esmond Snell 8Biochemistry for medics- Namrata Chhabra
  • 9. GOOD SOURCES Sources of Vitamin B6  Vitamin B6 is ABUNDANTLY present in:  Royal Jelly of Bees  Yeast  Rice Polishing  Cereal Grains  Egg Yolk  Germinal portion of various Seeds MODERATE SOURCES  Vitamin B6 is MODERATELY present in:  Liver  Kidney  Muscle  Fish POOR SOURCES  Vitamin B6 is POORLY present in:  Milk 9Biochemistry for medics- Namrata Chhabra
  • 10. Structure  Derivatives of Pyridine Ring Pyridine Ring 10Biochemistry for medics- Namrata Chhabra
  • 11. Structure  Derivatives of Pyridine Ring Purine RingPyridoxine 2-Methly, 3-Hydroxy, 4,5-diHydroxyMethly Pyridine  Pyridoxine 11Biochemistry for medics- Namrata Chhabra
  • 14. Structure  Derivatives of Pyridine  Pyridoxine  Also known as Pyridoxol  4th position contains a CH2OH group  Precursor from of Vitamin B6  Plant in origin Pyridoxine Pyridoxal Pyridoxamine  Pyridoxal  4th position contains a CHO group  Precursor from of Vitamin B6  Plant in origin  Pyridoxamine  4th position contains a CH2NH2 group  Precursor from of Vitamin B6  Plant in origin 14Biochemistry for medics- Namrata Chhabra
  • 15. Structure  Biochemically active only when Phosphorylated  Phosphorylation is brought about by Kinase enzyme  Phosphorylation occurs at 5th Position Pyridoxine Pyridoxine-P (Phosphate) Kinase 15Biochemistry for medics- Namrata Chhabra
  • 16. Structure  Pyridoxine  Also known as Pyridoxol  4th position contains a CH2OH group  Precursor from of Vitamin B6  Plant in origin  Pyridoxal  4th position contains a CHO group  Precursor from of Vitamin B6  Plant in origin  Pyridoxamine  4th position contains a CH2NH2 group  Precursor from of Vitamin B6  Plant in origin Pyridoxine Pyridoxal Pyridoxamine 16Biochemistry for medics- Namrata Chhabra
  • 18. Structure  Biochemically active only when Phosphorylated  Phosphorylation is brought about by Kinase enzyme  Phosphorylation occurs at 5th Position  In total, there are 6 isoforms of Vitamin B6: Pyridoxine Pyridoxine-P (Phosphate)  Pyridoxine  Pyridoxine-P  Pyridoxal  Pyridoxal-P  Pyridoxamine  Pyridoxamine-P 18Biochemistry for medics- Namrata Chhabra
  • 19. Structure  Biochemically active only when Phosphorylated  Phosphorylation is brought about by Kinase enzyme  Phosphorylation occurs at 5th Position  In total, there are 6 isoforms of Vitamin B6:  Pyridoxine  Pyridoxine-P  Pyridoxal  Pyridoxal-P  Pyridoxamine  Pyridoxamine-P  Pyridoxic Acid  Excretory form of Vitamin B6  Oxidation at 4th position Pyridoxic Acid NOTE: Vitamin B6 can also be excreted in the UNCHARGED form as Pyridoxine or Pyridoxal 19Biochemistry for medics- Namrata Chhabra
  • 20. Structure  Biochemically active only when Phosphorylated  Phosphorylation is brought about by Kinase enzyme  Phosphorylation occurs at 5th Position  In total, there are 6 isoforms of Vitamin B6:  Pyridoxine  Pyridoxine-P  Pyridoxal  Pyridoxal-P  Pyridoxamine  Pyridoxamine-P  Pyridoxic Acid  Excretory form of Vitamin B6  Oxidation at 4th position Pyridoxic Acid NOTE: Vitamin B6 can also be excreted in the UNCHARGED form as Pyridoxine or Pyridoxal 20Biochemistry for medics- Namrata Chhabra
  • 21. Activation of Vitamin B6  Biologically active forms are: a) Pyridoxal-PO4 b) Pyridoxamine-PO4 Pyridoxine Pyridoxal Pyridoxal-P Dehydrogenase Pyridoxal Kinase H2 ATP ADP Zn2+ Mg2+ 21Biochemistry for medics- Namrata Chhabra
  • 22. Role in Amino Acid Metabolism  Absorption is by either PASSIVE or ACTIVE mechanisms  Vitamin B6 is absorbed by ACTIVE TRANSPORT  Amino Acid Absorption 22Biochemistry for medics- Namrata Chhabra
  • 23. Role in Amino Acid Metabolism  General Amino Acid Reactions Transamination Reactions  SGPT (Serum Glutamate Pyruvate Transaminase) Glutamate Pyruvate 23Biochemistry for medics- Namrata Chhabra
  • 24. Role in Amino Acid Metabolism  General Amino Acid Reactions Transamination Reactions  SGPT (Serum Glutamate Pyruvate Transaminase) Glutamate Pyruvate 24Biochemistry for medics- Namrata Chhabra
  • 25. Role in Amino Acid Metabolism  General Amino Acid Reactions Transamination Reactions  SGPT (Serum Glutamate Pyruvate Transaminase) Glutamate PyruvateAlanine α-keto Glutarate 25Biochemistry for medics- Namrata Chhabra
  • 26. Role in Amino Acid Metabolism Pyridoxal-P Pyruvic Acid (Recipient α-keto acid) Glutamate (Donor α-amino acid) Mechanism of Reaction 26Biochemistry for medics- Namrata Chhabra
  • 27. Role in Amino Acid Metabolism Pyridoxal-P Pyruvic Acid (Recipient α-keto acid) Glutamate (Donor α-amino acid) Mechanism of Reaction 27Biochemistry for medics- Namrata Chhabra
  • 28. Pyridoxal-P Glutamate (Donor α-amino acid) Role in Amino Acid Metabolism Pyridoxal-P Pyruvic Acid (Recipient α-keto acid) Glutamate (Donor α-amino acid) α-keto Glutarate (New α-keto acid) Pyridoxamine-P Mechanism of Reaction 28Biochemistry for medics- Namrata Chhabra
  • 29. Pyruvic Acid (Recipient α-keto acid) Role in Amino Acid Metabolism Pyridoxal-P Pyruvic Acid (Recipient α-keto acid) Glutamate (Donor α-amino acid) α-keto Glutarate (New α-keto acid) Pyridoxamine-P Alanine (New α-amino acid) Pyridoxal-P Mechanism of Reaction 29Biochemistry for medics- Namrata Chhabra
  • 30. Role in Amino Acid Metabolism  General Amino Acid Reactions Transamination Reactions  SGPT (Serum Glutamate Pyruvate Transaminase) α-keto Glutarate (New α-keto acid) Alanine (New α-amino acid) Pyruvate (Recipient α-keto acid) Glutamate (Donor α-amino acid) SGPT B6-P + + 30Biochemistry for medics- Namrata Chhabra
  • 31. Role in Amino Acid Metabolism  General Amino Acid Reactions Transamination Reactions  SGPT (Serum Glutamate Pyruvate Transaminase) α-keto Glutarate (New α-keto acid) Alanine (New α-amino acid) Pyruvate (Recipient α-keto acid) Glutamate (Donor α-amino acid) SGPT B6-P + + 31Biochemistry for medics- Namrata Chhabra
  • 32. Role in Amino Acid Metabolism  General Amino Acid Reactions Transamination Reactions  SGPT (Serum Glutamate Pyruvate Transaminase) Pyruvate + Glutamate Alanine + α-keto Glutarate  SGOT (Serum Glutamate Oxaloacetate Transaminase) Oxaloacetate + Glutamate Aspartate + α-keto Glutarate CLINICAL SIGNIFICANCE  Synthesis of Non-Essential Amino Acids  Alanine  Aspartate  Recycling of Carbon Skeletons  Pyruvate  Oxaloacetate 32Biochemistry for medics- Namrata Chhabra
  • 33. Role in Amino Acid Metabolism  General Amino Acid Reactions Transamination Reactions  SGPT (Serum Glutamate Pyruvate Transaminase) Pyruvate + Glutamate Alanine + α-keto Glutarate  SGOT (Serum Glutamate Oxaloacetate Transaminase) Oxaloacetate + Glutamate Aspartate + α-keto Glutarate CLINICAL SIGNIFICANCE  Synthesis of Non-Essential Amino Acids  Alanine  Aspartate  Recycling of Carbon Skeletons  Pyruvate  Oxaloacetate 33Biochemistry for medics- Namrata Chhabra
  • 34. Role in Amino Acid Metabolism  General Amino Acid Reactions Deamination Reactions  Non-Oxidative Deamination Serine 34Biochemistry for medics- Namrata Chhabra
  • 35. Role in Amino Acid Metabolism  General Amino Acid Reactions Deamination Reactions  Non-Oxidative Deamination Dehydrase H2O B6-P H2ONH3 Serine Imino Acid Pyruvate Imino Acid 35Biochemistry for medics- Namrata Chhabra
  • 36. Role in Amino Acid Metabolism  General Amino Acid Reactions Deamination Reactions  Non-Oxidative Deamination Dehydrase H2O B6-P H2ONH3 Serine Imino Acid Pyruvate Imino Acid 36Biochemistry for medics- Namrata Chhabra
  • 37. Role in Amino Acid Metabolism  General Amino Acid Reactions Deamination Reactions  Non-Oxidative Deamination  Serine Deamination  Cysteine Deamination Serine Cysteine Pyruvate Pyruvate Water Hydrogen Sulphide + + Dehydrase B6-P Desulfhydrase B6-P CLINICAL SIGNIFICANCE  Breakdown of excess amino acids in Liver  Contributes to NH3 formation in the body NH3 NH3 37Biochemistry for medics- Namrata Chhabra
  • 38. Role in Amino Acid Metabolism  General Amino Acid Reactions Deamination Reactions  Non-Oxidative Deamination  Serine Deamination  Cysteine Deamination Serine Cysteine Pyruvate Pyruvate Water Hydrogen Sulphide + + Dehydrase B6-P Desulfhydrase B6-P CLINICAL SIGNIFICANCE  Breakdown of excess amino acids in Liver  Contributes to NH3 formation in the body NH3 NH3 38Biochemistry for medics- Namrata Chhabra
  • 39. Role in Amino Acid Metabolism  General Amino Acid Reactions Interconversion of Amino Acids  Racemases  Conversion of L-amino Acids to D-Amino Acids  Conversion of D-Amino Acids to L-Amino Acids RACEMASE B6-P L-AlanineD-Alanine 39Biochemistry for medics- Namrata Chhabra
  • 40. Role in Amino Acid Metabolism  General Amino Acid Reactions Interconversion of Amino Acids  Racemase  Conversion of L-amino Acids to D-Amino Acids  Conversion of D-Amino Acids to L-Amino Acids RACEMASE B6-P L-AlanineD-Alanine 40Biochemistry for medics- Namrata Chhabra
  • 41. Role in Amino Acid Metabolism  General Amino Acid Reactions Decarboxylation Reactions  Removal of CO2 to produce AMINES Histidine 41Biochemistry for medics- Namrata Chhabra
  • 42. Role in Amino Acid Metabolism  General Amino Acid Reactions Decarboxylation Reactions  Removal of CO2 to produce AMINES Decarboxylase B6-P CO2 Histidine 42Biochemistry for medics- Namrata Chhabra
  • 43. Role in Amino Acid Metabolism  General Amino Acid Reactions Decarboxylation Reactions  Removal of CO2 to produce AMINES Decarboxylase B6-P CO2 HistamineHistidine 43Biochemistry for medics- Namrata Chhabra
  • 44. Role in Amino Acid Metabolism  General Amino Acid Reactions Decarboxylation Reactions  Removal of CO2 to produce AMINES Decarboxylase B6-P CO2 HistamineHistidine 44Biochemistry for medics- Namrata Chhabra
  • 45. Role in Amino Acid Metabolism  General Amino Acid Reactions Decarboxylation Reactions  Removal of CO2 to produce AMINES Histidine 5-OH Tryptophan Glutamic Acid Histamine 5-OH Tryptamine (Serotonin) γ-Amino Butyric Acid Decarboxylase B6-P CO2 Decarboxylase B6-P CO2 Decarboxylase B6-P CO2 45Biochemistry for medics- Namrata Chhabra
  • 46.  Histamine  Synthesised by Basophils and Mast Cells  Mediator of Hypersensitivity Reactions  Triggers Inflammatory Reactions  Neurotransmitter in the Gut  γ-Amino Butyric Acid  Inhibitor Neurotransmitter in the CNS  GABA Deficiency produces a state of Hyper excitation  Convulsions  Precipitating factor for Epileptic Seizures  Serotonin  Neurotransmitter in CNS  Regulates Behaviour and Cognitive functions  Deficiency leads to Depression, Anxiety and Personality Disorders  Regulates Intestinal Motility in Gut Role in Amino Acid Metabolism CLINICAL SIGNIFICANCE 46Biochemistry for medics- Namrata Chhabra
  • 47. Role in Amino Acid Metabolism  Tryptophan Metabolism Tryptophan Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid NIACIN Kynureninase B6-P 47Biochemistry for medics- Namrata Chhabra
  • 48. Role in Amino Acid Metabolism  Tryptophan Metabolism Tryptophan Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid NIACIN Kynureninase B6-P CLINICAL SIGNIFICANCE  Pathway for Endogenous NIACIN synthesis  In Vitamin B6 deficiency  Niacin Deficiency  PELLAGRA sets in † Dermatitis 48Biochemistry for medics- Namrata Chhabra
  • 49. Role in Amino Acid Metabolism  Tryptophan Metabolism Tryptophan Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid NIACIN Kynureninase B6-P CLINICAL SIGNIFICANCE  Pathway for Endogenous NIACIN synthesis  In Vitamin B6 deficiency  Niacin Deficiency  PELLAGRA sets in † Dermatitis 49Biochemistry for medics- Namrata Chhabra
  • 50. Role in Amino Acid Metabolism  Tryptophan Metabolism Tryptophan Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid NIACIN Kynureninase B6-P CLINICAL SIGNIFICANCE  Pathway for Endogenous NIACIN synthesis  In Vitamin B6 deficiency  Niacin Deficiency  PELLAGRA sets in † Dermatitis † Dementia 50Biochemistry for medics- Namrata Chhabra
  • 51. Role in Amino Acid Metabolism  Tryptophan Metabolism Tryptophan Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid NIACIN Kynureninase B6-P CLINICAL SIGNIFICANCE  Pathway for Endogenous NIACIN synthesis  In Vitamin B6 deficiency  Niacin Deficiency  PELLAGRA sets in † Dermatitis † Dementia † Diarrhoea 51Biochemistry for medics- Namrata Chhabra
  • 52. Role in Amino Acid Metabolism  Tryptophan Metabolism Tryptophan Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid NIACIN Kynureninase B6-P CLINICAL SIGNIFICANCE  Pathway for Endogenous NIACIN synthesis  In Vitamin B6 deficiency  Niacin Deficiency  PELLAGRA sets in † Dermatitis † Dementia † Diarrhoea † DEATH 52Biochemistry for medics- Namrata Chhabra
  • 53. Role in Amino Acid Metabolism  Tryptophan Metabolism Tryptophan Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid NIACIN Kynureninase B6-P CLINICAL SIGNIFICANCE  Pathway for Endogenous NIACIN synthesis  In Vitamin B6 deficiency  Niacin Deficiency  PELLAGRA sets in † Dermatitis † Dementia † Diarrhoea † DEATH  In ISONIAZID therapy for Tuberculosis Isoniazid + Isoniazid B6-P Hydrasone B6-P 53Biochemistry for medics- Namrata Chhabra
  • 54. Role in Amino Acid Metabolism  Tryptophan Metabolism Tryptophan Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid NIACIN Kynureninase B6-P CLINICAL SIGNIFICANCE  Pathway for Endogenous NIACIN synthesis  In Vitamin B6 deficiency  Niacin Deficiency  PELLAGRA sets in † Dermatitis † Dementia † Diarrhoea † DEATH  In ISONIAZID therapy for Tuberculosis Isoniazid + Isoniazid B6-P Hydrasone B6-P B6-P 54Biochemistry for medics- Namrata Chhabra
  • 55. Role in Amino Acid Metabolism  Tryptophan Metabolism Tryptophan NIACIN CLINICAL SIGNIFICANCE  Pathway for Endogenous NIACIN synthesis  In Vitamin B6 deficiency  In ISONIAZID therapy for Tuberculosis  Tryptophan Loading Test Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid Kynureninase B6-P Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid Kynureninase B6-P 55Biochemistry for medics- Namrata Chhabra
  • 56. Role in Amino Acid Metabolism  Tryptophan Metabolism Tryptophan NIACIN CLINICAL SIGNIFICANCE  Pathway for Endogenous NIACIN synthesis  In Vitamin B6 deficiency  In ISONIAZID therapy for Tuberculosis  Tryptophan Loading Test Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid Kynureninase B6-P Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid Kynureninase B6-P Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid Kynureninase B6-P Xanthurenic Acid 56Biochemistry for medics- Namrata Chhabra
  • 57. Role in Amino Acid Metabolism  Tryptophan Metabolism Tryptophan NIACIN CLINICAL SIGNIFICANCE  Pathway for Endogenous NIACIN synthesis  In Vitamin B6 deficiency  In ISONIAZID therapy for Tuberculosis  Tryptophan Loading Test Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid Kynureninase B6-P Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid Kynureninase B6-P Kynurenine 3-OH-Kynurenine 3-OH-Anthranilic Acid Kynureninase B6-P Xanthurenic Acid 57Biochemistry for medics- Namrata Chhabra
  • 58. Role in Amino Acid Metabolism  Methionine Metabolism  Methionine metabolism occurs in 2 phases  Phase I - Conversion of Methionine to HOMOCYSTEINE  Phase II - Further metabolism of HOMOCYSTEINE Methionine HOMOCYSTEINE Serine+ Cystathionine CysteineHomoserine Cystathionine β SynthaseB6-P Cystathionine LyaseB6-P CLINICAL SIGNIFICANCE  Pathway for synthesis of Non-Essential Amino Acids like Cysteine  In Vitamin B6 deficiency  HOMOCYSTEINAEMIA  Homocysteine is Atherogenic  Ischaemic Heart Disease  Brain Stroke 58Biochemistry for medics- Namrata Chhabra
  • 59. Role in Amino Acid Metabolism  Glycine Metabolism Glycine HydroxyMethly THF Interconversion of Glycine to Serine 59Biochemistry for medics- Namrata Chhabra
  • 60. Serine Hydroxymethly Transferase B6-P Glycine Serine “Free” THF HydroxyMethly THF Role in Amino Acid Metabolism  Glycine Metabolism Interconversion of Glycine to Serine CLINICAL SIGNIFICANCE  Synthesis of Non-Essential Amino Acid Serine 60Biochemistry for medics- Namrata Chhabra
  • 61. Serine Hydroxymethly Transferase B6-P Glycine Serine “Free” THF HydroxyMethly THF Role in Amino Acid Metabolism  Glycine Metabolism Interconversion of Glycine to Serine CLINICAL SIGNIFICANCE  Synthesis of Non-Essential Amino Acid Serine 61Biochemistry for medics- Namrata Chhabra
  • 62. Tetra Hydro Folate B6-P GCS Glycine Role in Amino Acid Metabolism  Glycine Metabolism Glycine Cleavage System 62Biochemistry for medics- Namrata Chhabra
  • 63. Tetra Hydro Folate + N5,10 Methylene Tetra Hydro Folate B6-P GCS Glycine Role in Amino Acid Metabolism  Glycine Metabolism Glycine Cleavage System Carbon Dioxide Ammonia 63Biochemistry for medics- Namrata Chhabra
  • 64. + B6-P GCS Glycine Role in Amino Acid Metabolism  Glycine Metabolism Glycine Cleavage System CLINICAL SIGNIFICANCE dUMP dTMP Di Hydro Folate DNA Synthesis N5,10 Methylene Tetra Hydro Folate Thymidylate Synthase Carbon Dioxide Ammonia 64Biochemistry for medics- Namrata Chhabra
  • 65. + B6-P GCS Glycine Role in Amino Acid Metabolism  Glycine Metabolism Glycine Cleavage System CLINICAL SIGNIFICANCE dUMP dTMP Di Hydro Folate DNA Synthesis Thymidylate Synthase Carbon Dioxide Ammonia N5,10 Methylene Tetra Hydro Folate 65Biochemistry for medics- Namrata Chhabra
  • 66. GlycineAcetyl CoA + Role in Amino Acid Metabolism  Glycine Metabolism Synthesis of Amino Acetone 66Biochemistry for medics- Namrata Chhabra
  • 67. GlycineAcetyl CoA Amino Acetone Synthetase B6-P + Role in Amino Acid Metabolism  Glycine Metabolism Synthesis of Amino Acetone 67Biochemistry for medics- Namrata Chhabra
  • 68. Amino Acetone GlycineAcetyl CoA Amino Acetone Synthetase B6-P + Role in Amino Acid Metabolism  Glycine Metabolism Synthesis of Amino Acetone CLINICAL SIGNIFICANCE  Amino Acetone has a role in Metabolism† † Elliott, W.H., et al., 1959. Amino Acteone: Its Isolation and Role in Metabolism, Canberra. Nature: 183, 1051-1052. 68Biochemistry for medics- Namrata Chhabra
  • 69.  Sources of Vitamin B6  Structure of Vitamin B6  Activation of Vitamin B6  Role in Amino Acid Metabolism  General Amino Acid Reactions  Metabolism of Tryptophan  Metabolism of Methionine  Metabolism of Glycine SUMMARY 69Biochemistry for medics- Namrata Chhabra
  • 70.  Biehl, J.P., et al., 1954. Effect of Isoniazid on Vitamin B6 Metabolism; Its Possible Significance in Producing Isoniazid Neuritis, London. Royal Society of Medicine Press; 85:389-392.  Robinson, K., et al., 1996. Hyperhomocysteinemia Confers an Independent Increased Risk of Atherosclerosis in End-Stage Renal Disease and Is Closely Linked to Plasma Folate and Pyridoxine Concentrations, Boston. Circulation; 94:2743-2748 Bibliography  Chatterjea, M.N., Shinde, R., 2008. Textbook of Medical Biochemistry, 7th Edition, New Delhi. Jaypee.  Murray, R.K., et al., 2009. Harper’s Illustrated Biochemistry, 28th Edition, New York. McGraw Hill.  Champe, C., et al., 2008. Lippincott’s Illustrated Review of Biochemistry, 4th Edition , New York. Lippincott Williams and Wilkins.  Chabba, N., 2011. Vitamin B6 chemistry, Activation and Role in Amino Acid Metabolism. Biochemistry Lecture, Mauritius, SSR Medical College. UNPUBLISHED. 70Biochemistry for medics- Namrata Chhabra
  • 71. 71Biochemistry for medics- Namrata Chhabra