Metal alteration of uroporphyrinogen decarboxylase and coproporphyrinogen oxidase.
Both UD and CO are susceptible to alteration by sulfhydryl-directed binding agents including a variety of trace metals. UD apparently requires a functional SH group or groups for catalytic activity, and the various steps of decarboxylation catalyzed by the enzyme can be differentially inhibited by divalent cations such as Hg2+ at very low concentrations. There is evidence that tissue-specific factors such as the endogenous GSH concentration may influence the susceptibility of UD in some tissues to metal inhibition, and this circumstance could be highly relevant to the etiology of porphyrinopathies or porphyrinurias that arise during prolonged metal exposures. CO does not appear to have a requirement for functional SH groups at the active site, but several SH groups on the enzyme appear to be involved in maintaining the protein's noncovalent structural characteristics. CO appears to be substantially more readily inhibited by metals in vivo than in vitro. This observation may reflect effects of metals on both the structural integrity of the enzyme is functionally associated in the intact cell. Finally, it seems reasonable to suggest that tissues, such as the kidney, that ordinarily contribute only sparingly to total excreted porphyrin levels may assume increased importance in this regard when challenged by specific porphyrinogenic chemicals such as trace metals. Advantage might be taken of such chemical- and organ-specific changes in porphyrin metabolism and porphyrin excretion patterns in monitoring prolonged, subclinical exposure to such chemicals in human populations.
Woods
J S
JS
Battelle Seattle Research Center, Seattle, Washington 98105.
Fowler
B A
BA
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D003304:Coproporphyrinogen Oxidase / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008670:Metals / Q000494:pharmacology*; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism*
D008670:Metals; D010088:Oxidoreductases; D003304:Coproporphyrinogen Oxidase; D002262:Carboxy-Lyases; D014575:Uroporphyrinogen Decarboxylase