CHEM430 Study Guide - Final Guide: Tyrosine-Kinase Inhibitor, Hmg-Coa Reductase, Aromatic L-Amino Acid Decarboxylase
29 Mar 2016
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Converted to napqi via glutathione conjugation cyp450. If overdosed metabolic pathway can deplete glutathione in the liver and cause severe/fatal liver toxicity. It inhibits cox by intercepting the activation of tyrosine 385 by reducing heme itself. Has good activity on neurons and sensory cells (suppressing pain and fever) but has little effect on pro inflammatory prostaglandins. Salicylic acid is a non-covalent inhibitor however acetylsalicylic acid is a covalent inhibitor so explains long lasting effects. Example of non-ionic diffusion to prevent accumulation of acetylsalicylic acid in gastric mucosal cells, drug is given enteric coating that resists degradation at low ph but easily dissolves at alkaline ph of small intestine (diagram on pg 40) Modifies serine 350 in the active site of cox 1. Prevents access of arachidonic acid to the catalytic tyrosine and inactivates enzyme. Also acetylates the homologous serine residue in cox 2.
