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.

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Abstract
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.

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