Effect of endotoxin on tryptophan pyrrolase and delta-aminolaevulinate synthase: evidence for an endogenous regulatory haem fraction in rat liver.
Endotoxin was administered to rats at a dose shown previously to stimulate hepatic haem oxygenase activity and to block induction of delta-aminolaevulinate synthase, apparently by causing redistribution of haem from cytochrome P-450 to a regulatory haem pool in the liver. Within 5h of the administration of endotoxin (at a time when the effect of the compound on cytochrome P-450 is maximal) the relative saturation of tryptophan pyrrolase with intrinsic haem rose, from a basal value of 50% to 90%, indicating that 'free' haem had become available. Concurrently, the activity of delta-aminolaevulinate synthase was decreased to 25% of its basal value. Haem oxygenase reached peak activity 13h after endotoxin administration. These findings provide new evidence for the existence of an 'unassigned' hepatic haem fraction, which exchanges with cytochrome P-450 haem and regulates these three enzyme functions.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism*; D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D006418:Heme / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D051381:Rats; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D004731:Endotoxins; D006418:Heme; D006899:Mixed Function Oxygenases; D014366:Tryptophan Oxygenase; D000624:5-Aminolevulinate Synthetase