PCL201H1 Lecture Notes - Lecture 13: Hydrolase, Aplastic Anemia, Methylation
11 Jan 2018
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Reduction: doxorubicin: por reduces to reactive semi-quinone radical, cytotoxic species forms, quinone reductase detoxi es to hydroquinone. Glucuronidation: udp-glucuronosyltransferase (ugt, works on acetominophen, morphine, udpga cofactor, transfers glucuronic acid to molecules, gilbert"s syndrome: de ciency in ugt, bilirubin not eliminated, jaundice, crigler-najjar: severe de ciency, hyperbilirubinemia, aplastic anemia from chloramphenicol. Glutathione: glutathione s-transferase (gst, electrophilic centres, gsh cofactor (reduced glutathione, glu-cys-gly, after added: enzymes remove gly, glu and n-acetylate cysteine group to mercapturic acid. Sulfation: sulfotransferase (sult, cytoplasm, acetominophen, steroids (phenols, paps cofactor, transfers so3 group to drug. Acetylation: n-acetyl transferase (nat, cytoplasm, amines and hydrazine, acetyl-coa cofactor. Methylation: methyltransferase (mt, cytoplasm, 6-mercaptopurine (tmpt, sam cofactor, inactivates 6mp anti-cancer drug, polymorphism important in leukemia therapy. Acetaminophen hepatotoxicity: overdose: inactivation via glucuronidation and sulfation, 3a4 and 2e1 convert to napqi, gst works on napqi to detoxify: nac restores gsh pools, all saturated: go to nucleophilic proteins and liver cell death.
