Detoxification Mechanisms-NEW - DETOXIFICATION MECHANISMS...

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1 DETOXIFICATION MECHANISMS Dr. V. JAGADEESAN Former Deputy Director (Sr. Gr.) FOOD AND DRUG TOXICOLOGY RESEARCH CENTRE NATIONAL INSTITUTE OF NUTRITION Indian Council of Medical Research HYDERABAD – 500 007
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2 1. What is the need ? 2. Xenobiotics Vs Endobiotics 3. Essential feature of detoxification Two categories of Detoxification Phase I Phase II Functionalisation Synthetic or conjugating Reactions reactions 4. Act on Foreign compds. as well as a. Glucuronic acid endogenous substrates like b. Glutathione fatty acids, cholesterol, c. Glycine bile acids, steroids d. Sulphate DETOXIFICATION MECHANISMS
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3 BIOTRANSFORMATION Stepwise biotransformation is necessary since many parent compounds lack a functional group to which a larger molecule can be attached. Therefore Phase I adds the necessary functional group and Phase II attaches a larger molecule.
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4 THE ENZYMES OF XENOBIOTIC BIOTRANSFORMATION Phase I Phase II Cytochrome P450 Glutathione Transferases NADPH-Cytochrome P450 reductase UDP-glucuronyl transferases Flvin containing monooxygenases Sulfotransferases Alcoholdehydrogenase N-acetyltransfeases Dihydrodiol dehydrogenase Thiol transferase Glutathione peroxidase Amino acid transferases Monoamine Oxidase Xanthine Oxidase Quinine reductase Epoxide hydrolase Esterases
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5 Location : Liver Skin Small Intestines Lungs Kidneys Spleen To a very little Brain extent THE ENZYMES OF XENOBIOTIC BIOTRANSFORMATION
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Endoplasmic Reticulum : Microsomes MFO : Mixed Function Oxidases are those oxidations in which one atom of molecular oxygen is reduced to water while the other is incorporated into substrate. Hence mono oxygenase.
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Detoxification Mechanisms-NEW - DETOXIFICATION MECHANISMS...

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