Studies on porphyrin metabolism in the kidney. Effects of trace metals and glutathione on renal uroporphyrinogen decarboxylase.
Uroporphyrinogen (urogen) decarboxylase catalyzes the decarboxylation of 8- to 4-carboxyl porphyrinogen during heme biosynthesis in mammalian tissues. The specific activity of renal urogen decarboxylase was shown to be approximately one-third that of the hepatic enzyme and to be readily inactivated by HgCl2 following acute treatment or at concentrations as low as 50 microM in vitro. HgCl2 differentially inhibited the decarboxylation of 8- to 7- and 7- to lesser-carboxylated porphyrinogens in the kidney, suggesting that at least a two-stage process is involved in the catalytic action of the renal enzyme. In contrast, neither lead nor iron compounds inhibited renal urogen decarboxylase in concentrations as high as 1 mM in the reaction mixture. GSH increased renal but not hepatic urogen decarboxylase activity by over 4-fold in vitro when measured as total porphyrinogen products produced, and preferentially accelerated the decarboxylation of 7- to 4-carboxyl porphyrinogen. GSH also protected the renal enzyme from HgCl2 inhibition. These findings suggest that renal urogen decarboxylase catalyzes porphyrin decarboxylation significantly less rapidly than the hepatic enzyme, is readily inactivated by mercuric chloride, and may be GSH-dependent with respect to achieving optimal catalytic activity. These observations may be useful in characterizing the contribution of the kidney to the clinical manifestations of the inherited porphyrias and environmentally induced disorders of porphyrin metabolism.
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology*; D011165:Porphyrinogens / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity; D014131:Trace Elements / Q000378:metabolism*; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism*
D011165:Porphyrinogens; D014131:Trace Elements; D008627:Mercuric Chloride; D002262:Carboxy-Lyases; D014575:Uroporphyrinogen Decarboxylase; D005978:Glutathione