Sn-protoporphyrin rapidly and markedly enhances the heme saturation of hepatic tryptophan pyrrolase. Evidence that this synthetic metalloporphyrin increases the functional content of heme in the liver.
Sn-protoporphyrin is a potent competitive inhibitor of heme oxygenase, the rate-limiting enzyme in heme degradation to bile pigment, and has been successfully utilized to suppress hyperbilirubinemia in a variety of experimental and naturally occurring forms of jaundice in animals and man. The compound is presumed to act in vivo primarily by inhibiting heme oxidation; thus it would be reasonable to expect that preservation of some functional moiety of cellular heme from degradation by heme oxygenase would occur after Sn-protoporphyrin administration. We have examined this question in liver by studying the heme saturation of tryptophan pyrrolase, the heme-dependent enzyme which controls the first and rate-limiting step in the catabolism of L-tryptophan. Sn-protoporphyrin, in doses (10 mumol/kg body wt) which entirely suppress neonatal hyperbilirubinemia in the experimental animal, leads to a very rapid (approximately 30-60 min) increase in the heme saturation of tryptophan pyrrolase from normal levels of approximately 50-60% to nearly 100%. The effect peaks at 1-2 h and lasts for at least 12 h. Sn-protoporphyrin is also able to block the rapid and marked decline in heme saturation of tryptophan pyrrolase elicited by inorganic cobalt, a potent inducer of heme oxygenase in liver. These findings establish clearly that after the administration of Sn-protoporphyrin in the whole animal, a functionally active heme pool, the one related to tryptophan pyrrolase, is rapidly increased in liver, confirming that the metalloporphyrin inhibits the degradation of endogenous heme by heme oxygenase.
D000818:Animals; D003035:Cobalt / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006418:Heme / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008665:Metalloporphyrins; D011166:Porphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D008665:Metalloporphyrins; D011166:Porphyrins; D011524:Protoporphyrins; D003035:Cobalt; D006418:Heme; C032628:tin protoporphyrin IX; D014366:Tryptophan Oxygenase; C018021:cobaltous chloride