Studies on the mechanisms of thallium-mediated inhibition of hepatic mixed function oxidase activity. Correlation with inhibition of NADPH-cytochrome c (P-450) reductase.
Thallium (TlCl3) administration to rats produced a dose-dependent loss of hepatic NADPH-cytochrome c (P-450) reductase and microsomal mixed function oxidase activities within 2-4 hr following treatment. These changes occurred independently of apparent effects on microsomal heme or cytochrome P-450 content, both of which remained unchanged with respect to control levels despite transient inhibition of delta-aminolevulinic acid (ALA) synthetase and induction of heme oxygenase. These results are consistent with the recognized properties of thallium as both a flavoprotein antagonist and sulfhydryl inhibitor and differ uniquely from the action of other metals which impair mixed function oxidase activity through compromise of heme biosynthesis and heme depletion. The potential utility of thallium compounds in further evaluating the functional characteristics of NADPH-cytochrome c (P-450) reductase and its role in microsomal oxidative processes is suggested from these observations.
D000624:5-Aminolevulinate Synthetase / Q000037:antagonists & inhibitors; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004229:Dithiothreitol / Q000494:pharmacology; D006418:Heme / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009251:NADPH-Ferrihemoprotein Reductase / Q000037:antagonists & inhibitors*; D051381:Rats; D013793:Thallium / Q000494:pharmacology*
D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D013793:Thallium; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase; D000624:5-Aminolevulinate Synthetase; D004229:Dithiothreitol