Tryptophan pyrrolase in heme metabolism. Comparative actions of inorganic tin and cobalt and their protoporphyrin chelates on tryptophan pyrrolase in liver.

The effects of various metals and metalloporphyrins, which are known to alter markedly heme metabolism in vivo, on the heme saturation of tryptophan pyrrolase in liver were examined. At early time points, up to 120 min, administration of CoCl2 to rats caused a rapid and marked decrease in the degree of heme saturation of tryptophan pyrrolase; in contrast, Co-protoporphyrin produced a slight increase in heme saturation of the enzyme. SnCl2 did not alter the heme saturation of tryptophan pyrrolase; however, treatment of rats with Sn-protoporphyrin, a potent competitive inhibitor of heme oxygenase activity both in vivo and in vitro, produced a rapid and complete heme saturation of tryptophan pyrrolase. In addition, upon simultaneous administration of Sn-protoporphyrin and CoCl2, Sn-protoporphyrin prevented the CoCl2-mediated decrease in heme saturation of tryptophan pyrrolase. These findings provide further evidence that the measurement of the heme saturation of tryptophan pyrrolase is a sensitive indicator of changes in the availability of heme in the "regulatory" heme pool, particularly in the immediate period after administration of compounds which are known to perturb heme metabolism in vivo.