The document discusses vitamin B6 and its role in amino acid metabolism. It covers the history, sources, structures and isoforms of vitamin B6. The key active forms are pyridoxal phosphate and pyridoxamine phosphate. Vitamin B6 is required for important amino acid reactions like transamination and deamination. Transamination reactions involve the interconversion of amino acids and alpha-keto acids using vitamin B6 as a cofactor. They are important for synthesizing non-essential amino acids and recycling carbon skeletons. Deamination reactions remove amino groups from amino acids, producing ammonia, and use vitamin B6 cofactors.
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
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
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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+
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22. Role in Amino Acid Metabolism
Absorption is by either PASSIVE or ACTIVE mechanisms
Vitamin B6 is absorbed by ACTIVE TRANSPORT
Amino Acid Absorption
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23. Role in Amino Acid Metabolism
General Amino Acid Reactions
Transamination Reactions
SGPT (Serum Glutamate Pyruvate Transaminase)
Glutamate Pyruvate
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24. Role in Amino Acid Metabolism
General Amino Acid Reactions
Transamination Reactions
SGPT (Serum Glutamate Pyruvate Transaminase)
Glutamate Pyruvate
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25. Role in Amino Acid Metabolism
General Amino Acid Reactions
Transamination Reactions
SGPT (Serum Glutamate Pyruvate Transaminase)
Glutamate PyruvateAlanine α-keto Glutarate
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26. Role in Amino Acid Metabolism
Pyridoxal-P
Pyruvic Acid
(Recipient α-keto acid)
Glutamate
(Donor α-amino acid)
Mechanism of Reaction
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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
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
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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
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59. Role in Amino Acid Metabolism
Glycine Metabolism
Glycine
HydroxyMethly THF
Interconversion of Glycine to Serine
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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