The induction of heme oxidation in various tissues by trace metals: evidence for the catabolism of endogenous heme by hepatic heme oxygenase.

Cobalt is a potent inducer of hepatic heme oxygenase and concomitantly decreases microsomal cytochrome P-450 content in liver cells. Studies in which microsomal heme was labelled with 14C-beta-aminolevulinic acid showed that the decline observed in P-450 follows the induction of heme oxygenase indicating that endogenous heme is a substrate for this enzyme. The inducing effect of cobalt on heme oxygenase in liver extended to other organs such as heart, renal cortex and medulla, lungs and intestinal mucosa but not to the spleen and brain. In kidney and heart, cobalt resulted in decreases in microsomal and mitochondrial contents of hemoproteins. In addition ALAS activity of kidney was depressed by the metal. Other metals which chelate with sulfhydryl groups (e.g., Cr, Fe, Ni, Cu, Zn, Cd, Hg, Pb) were also shown to induce heart and renal heme oxygenase activities. Covalent binding of cobalt with mercaptans inactivated the metal with respect to its induction of heme oxygenase and degradation of hemoproteins.