Detoxification Mechanisms – Part II

Detoxification Mechanisms – Part II -...

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    1 Detoxification Mechanisms – Part II Dr.V.Jagadeesan Former Deputy Director (Sr. Grade) National Institute of Nutrition
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    2 Relationship between drug metabolism  and DNA adduct formation
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    3 Reaction Mechanism
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    4 Biotransformation – Phase I
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    5 Aromatic hydroxylations – Phase I
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    6 Glutathione Conjugation – Phase II
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    7 Glucuronidation – Phase II
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    8 Acetylation Phase II Conjugation   Relevant Enzyme :  “Acetyl CoA dependent N-acetyl transferase” Common Xenobiotic substrate Isoniazid Benzidine Procainamide PABA
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    9 Low at birth  Ontogenic Development  Depressed in old age DM Capacity
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    10 Proteins  - Apoenzymes and cell function  Carbohydrates  - Overall cell functions  Lipids  Vit. A.  - Membrane structure  Vit. E  Riboflavin  - Flavoprotein component of Cyt P450  reduct.  Niacin  - NADPH (essen. Cofactor)  Pyridoxine  - heam synthesis  Iron - hemoprotein Copper - heam synthesis (ferrochelatase)  Ca, Mg, K  - Role of nutrients in drug metabolism
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    11 Effect of various Nutrients/Nutrient  deficiencies on DME Nutrient Deficiency Effect Observed Fasting  Cyt P 450 Energy  Cyt P 450  Protein  Cyt P 450 Fat  High PUFA  Fat free diet  Cyt P 450  Cyt P 450 Riboflavin  Cyt P 450  reductase
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    12 Effect of various Nutrients/ Nutrient  deficiencies on DME Nutrient Deficiency Effect Observed Vitamin C  Cyt P 450  reductase Vitamin A  Cyt P 450  reductase Vitamin E  Cyt P 450  reductase Iron  AHH,AD,MEH,UDPGT Zinc  AHH,AD,MEH,UDPGT  GST Magnesium  Cyt P 450  , NADPH Oxidase
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    13 Schematic representation of the sequence of  events following expose to toxic chemicals
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    14 DNA Adduct Formations Preferred Sites Adenine N-1 N-3 N-7 Guanine N-3 O-6 N-7 Cytosine O-2 N-2 Thymine O-2 N-3
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Detoxification Mechanisms – Part II -...

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