title: Hepatic haem metabolism in porphyria cutanea tarda (PCT): enzymatic studies and their relation to liver ultrastructure.
abstract: Hepatic levels of cytochrome P-450 are elevated more than 4-fold in porphyria cutanea tarda (PCT) but not in other hepatic porphyrias or in non-porphyrics with alcoholic liver disease. In this study the ability of liver homogenates to metabolise aminopyrine and benzpyrene was correlated with hepatic cytochrome P-450 levels and with liver ultrastructure. The Km and Vmax for aminopyrine-N-demethylation and for benzpyrene hydroxylation exhibited a wide range of values with no significant differences between PCT patients and nonporphyric controls. Proliferation of the hepatic smooth endoplasmic reticulum in PCT was not significantly different from that observed in liver tissue obtained from patients with variegate porphyria or protoporphyria. Kushner reported data suggesting diminished uro'gen-I-decarboxylase activity as the autosomal dominantly inherited metabolic defect in PCT. Red cell uro'gen-I-decarboxylase activity was measured in 5 PCT males and 4 PCT females and activities were compared with 16 sex- and age-matched non-porphyric control patients. There was no significant difference in uro'gen-I-decarboxylase activity in the PCT and non-porphyric patients nor was there any significant difference relating to the sex of the patient. The role of iron in PCT was studied indirectly using the hexachlorobenzene porphyric rat as the rodent model.
mesh_terms: D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism; D002262:Carboxy-Lyases / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006418:Heme / Q000378:metabolism*; D006581:Hexachlorobenzene / Q000494:pharmacology; D006801:Humans; D006900:Hydroxylation; D007501:Iron / Q000494:pharmacology; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D011164:Porphyrias / Q000201:enzymology / Q000378:metabolism*; D011166:Porphyrins / Q000378:metabolism; D051381:Rats
chemical_list: D001580:Benzopyrenes; D011166:Porphyrins; D000632:Aminopyrine; D006418:Heme; D006581:Hexachlorobenzene; D003577:Cytochrome P-450 Enzyme System; D007501:Iron; D002262:Carboxy-Lyases