Defective human erythrocyte uroporphyrinogen decarboxylase in familial porphyria cutanea tarda: the metabolic lesion or the result of endogenous porphyrinemia?
We have demonstrated that oral charcoal therapy is as effective as therapeutic phlebotomy in reducing porphyrinemia in porphyria cutanea tarda. The effects of immediate and sustained reduction of porphyrinemia on the catalytic properties of partially purified (approximately 200-fold) preparations of red cell uroporphyrinogen decarboxylase of a patient with familial porphyria cutanea tarda were studied. All populations of the patient's red cells exhibited defective enzyme activity, and the apparent Michaelis constants (Km) determined with penta-, hepta-, and octa-carboxylic I porphyrinogen substrates were approximately 3-4 times higher as compared to the normal controls. Mixing experiments (normal and defective enzyme), and preincubation of the normal enzyme with porphyric plasma prior to purification, yielded data supporting the concept that the catalytic defects of red cell uroporphyrinogen decarboxylase in familial porphyria cutanea tarda are independent of interactions between circulating endogenous porphyrins and the enzyme.
Mukerji
S K
SK
Department of Internal Medicine, School of Medicine, University of California, Davis, Sacramento 95817.
Pimstone
N R
NR
D002262:Carboxy-Lyases / Q000097:blood*; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D011164:Porphyrias / Q000097:blood / Q000201:enzymology*; D011166:Porphyrins / Q000097:blood*; D012016:Reference Values; D012871:Skin Diseases / Q000097:blood / Q000201:enzymology*; D014575:Uroporphyrinogen Decarboxylase / Q000097:blood* / Q000172:deficiency
D011166:Porphyrins; D002262:Carboxy-Lyases; D014575:Uroporphyrinogen Decarboxylase