Inhibition of uroporphyrinogen I synthase activity and depression of microsomal heme and cytochrome P-450 in rat liver by bilirubin.
Purified rat hepatic uroporphyrinogen (UROgen) I synthase (URO-S) was inhibited by bilirubin or the ditaurine derivative. Inhibition was reversible and non-competitive to the substrate porphobilinogen (PBG). The inhibition constants (Ki values) for bilirubin and the conjugate were 1.5 microM and 0.26 microM respectively. Rats afflicted with hyperbilirubinemia caused by biliary obstruction had decreased levels of hepatic microsomal heme (58% of control) and cytochrome P-450 (60% of control) at day 3. Hepatic delta-aminolevulinic acid synthetase (ALAS) activity was increased (39% of control) at day 3.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000642:Ammonia-Lyases / Q000037:antagonists & inhibitors*; D000818:Animals; D001663:Bilirubin / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006418:Heme / Q000032:analysis*; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006932:Hyperbilirubinemia / Q000503:physiopathology; D008297:Male; D008862:Microsomes, Liver / Q000032:analysis / Q000187:drug effects* / Q000201:enzymology; D051381:Rats
D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D000624:5-Aminolevulinate Synthetase; D011163:Hydroxymethylbilane Synthase; D000642:Ammonia-Lyases; D001663:Bilirubin