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Vitamin B6- Phosphate- Chemistry, activation and role in amino acid metabolism
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Biochemistry For Medicswww.namrata.co
Best Seminar till dateAccepted for publication in Biochemistry for medicsIn Student’s corner
Presented By: RAMESSUR: KAVISH S.A.(ROLL NUMBER: 95)
VITAMIN B-6 CHEMISTRY, ACTIVATION AND ROLE IN AMINO ACID METABOLISM
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
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
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)
INTRODUCTION:
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
INTRODUCTION:
B-Complex Vitamins
INTRODUCTION: 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
HISTORY:
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
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
Structure Derivatives of Purine Ring
Purine Ring
Structure Derivatives of Purine Ring
Purine RingPyridoxine
2-Methly, 3-Hydroxy, 4,5-diHydroxyMethly Pyridine
Pyridoxine
Structure
Pyridoxal
Purine RingPyridoxal
Structure
Pyridoxamine
Purine RingPyridoxamine
Structure Derivatives of Purine Ring
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
Structure
Biochemically active only when Phosphorylated Phosphorylation is brought about by Kinase enzyme Phosphorylation occurs at 5th Position
Pyridoxine Pyridoxine-P (Phosphate)
Kinase
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
Structure
Pyridoxine
Pyridoxal
Pyridoxamine
Pyridoxine-P
Pyridoxal-P
Pyridoxamine-P
Kinase
Kinase
Kinase
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
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
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
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+
Role in Amino Acid Metabolism
Absorption is by either PASSIVE or ACTIVE mechanisms Vitamin B6 is absorbed by ACTIVE TRANSPORT
Amino Acid Absorption
Role in Amino Acid Metabolism
General Amino Acid Reactions
Transamination Reactions SGPT (Serum Glutamate Pyruvate Transaminase)
Glutamate Pyruvate
Role in Amino Acid Metabolism
General Amino Acid Reactions
Transamination Reactions SGPT (Serum Glutamate Pyruvate Transaminase)
Glutamate Pyruvate
Role in Amino Acid Metabolism
General Amino Acid Reactions
Transamination Reactions SGPT (Serum Glutamate Pyruvate Transaminase)
Glutamate PyruvateAlanine α-keto Glutarate
Role in Amino Acid Metabolism
Pyridoxal-P
Pyruvic Acid (Recipient α-keto acid)
Glutamate(Donor α-amino acid)
Mechanism of Reaction
Role in Amino Acid Metabolism
Pyridoxal-P
Pyruvic Acid (Recipient α-keto acid)
Glutamate(Donor α-amino acid)
Mechanism of Reaction
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
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
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+ +
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+ +
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
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
Role in Amino Acid Metabolism
General Amino Acid Reactions
Deamination Reactions Non-Oxidative Deamination
Serine
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
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
Role in Amino Acid Metabolism
General Amino Acid Reactions
Deamination Reactions Non-Oxidative Deamination
Serine Deamination
Cysteine DeaminationSerine
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
Role in Amino Acid Metabolism
General Amino Acid Reactions
Deamination Reactions Non-Oxidative Deamination
Serine Deamination
Cysteine DeaminationSerine
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
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
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
Role in Amino Acid Metabolism
General Amino Acid Reactions
Decarboxylation Reactions Removal of CO2 to produce AMINES
Histidine
Role in Amino Acid Metabolism
General Amino Acid Reactions
Decarboxylation Reactions Removal of CO2 to produce AMINES
Decarboxylase
B6-P
CO2
Histidine
Role in Amino Acid Metabolism
General Amino Acid Reactions
Decarboxylation Reactions Removal of CO2 to produce AMINES
Decarboxylase
B6-P
CO2
HistamineHistidine
Role in Amino Acid Metabolism
General Amino Acid Reactions
Decarboxylation Reactions Removal of CO2 to produce AMINES
Decarboxylase
B6-P
CO2
HistamineHistidine
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
DecarboxylaseB6-P
CO2
DecarboxylaseB6-P
CO2
DecarboxylaseB6-P
CO2
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
Role in Amino Acid Metabolism
Tryptophan Metabolism
Tryptophan
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
NIACIN
Kynureninase
B6-P
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
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
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
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
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
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 TuberculosisIsoniazid
+
Isoniazid B6-P Hydrasone
B6-P
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 TuberculosisIsoniazid
+
Isoniazid B6-P Hydrasone
B6-P
B6-P
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 TestKynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
Kynureninase
B6-P
Kynurenine
3-OH-Kynurenine
3-OH-Anthranilic Acid
Kynureninase
B6-P
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 TestKynurenine
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-PXanthurenic Acid
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 TestKynurenine
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-PXanthurenic Acid
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
Role in Amino Acid Metabolism
Glycine Metabolism
Glycine
HydroxyMethly THF
Interconversion of Glycine to Serine
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
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
Tetra Hydro Folate
B6-P
GCSGlycine
Role in Amino Acid Metabolism
Glycine Metabolism
Glycine Cleavage System
Tetra Hydro Folate
+
N5,10 Methylene Tetra Hydro Folate
B6-P
GCSGlycine
Role in Amino Acid Metabolism
Glycine Metabolism
Glycine Cleavage System
Carbon Dioxide Ammonia
+B6-P
GCSGlycine
Role in Amino Acid Metabolism
Glycine Metabolism
Glycine Cleavage System
CLINICAL SIGNIFICANCE
dUMP dTMP
Di Hydro Folate
DNA SynthesisN5,10 Methylene Tetra Hydro Folate
Thymidylate Synthase
Carbon Dioxide Ammonia
+B6-P
GCSGlycine
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
GlycineAcetyl CoA
+
Role in Amino Acid Metabolism
Glycine Metabolism
Synthesis of Amino Acetone
GlycineAcetyl CoA
Amino Acetone Synthetase
B6-P
+
Role in Amino Acid Metabolism
Glycine Metabolism
Synthesis of Amino Acetone
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.
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
+ RELEVANT CLINICAL SIGNIFICANCES
TEXTBOOKS
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.
SCIENTIFIC PAPERS
LECTURE NOTES Chabba, N., 2011. Vitamin B6 chemistry, Activation and Role in Amino Acid
Metabolism. Biochemistry Lecture, Mauritius, SSR Medical College. UNPUBLISHED.
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