Biotransformation

1. BIOTRANSFORMATION

2. Biochemical alteration of chemicals such as (but not limited to) nutrients, amino acids, toxins, and drugs in the body It is also needed to render nonpolar compounds polar so that they are not reabsorbed in renal tubules and are excreted . The body typically deals with a foreign compound (DRUGS) by making it more water-soluble, to increase the rate of its excretion through the urine

3. Site and enzymes used in biotransformation Site : usually liver Enzymes:

4. Enzymes Microsomal enzymes A group of enzymes associated with a certain particulate fraction of liver homogenate. These are a mixed function oxidase system or monooxygenases . These requires NADPH and oxygen. Non microsomal enzymes These are present in the cytoplasm and mitochondria of hepatic cells as well as in other tissues including plasma. The 2 most imp. Microsomal enzymes: NADPH cyt . P450 reductase Cut. P450

5. Phases of biotransformation

6. Phase I reactions Oxidation Reduction Hydrolysis

7. Oxidation reactions Process of addition of oxygen or removal of hydrogen from a drug molecule.

8. Reduction reactions Addition of hydrogen or removal of oxygen from a drug molecule. Nitro reduction : chloramphenicol  arylamine Keto reduction: cortisone  hydrocortisone

9. Hydrolysis Process where a drug molecule is split by the addition of a molecule of water. Both microsomal and non- microsomal enzymes maybe involved. Eg : acetylcholine+ H2O  choline + acetic acid

10. Phase 2 reactions

11. Glucuronide conjugation Most common type of metabolic reaction Drug + UDPGA drug glucuronide + UDP Glucuronyl transferase excreted

12. Glutathione conjugation Glutathione –s – transferase

13. Sulfate conjugation Enzyme : sulfotransferases

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