title: A potential biochemical explanation for the genesis of porphyria cutanea tarda. Studies on the inherent biochemical defect in highly purified human erythrocyte uroporphyrinogen decarboxylase and its amplification by iron.
abstract: Familial porphyria cutanea tarda (PCT) is a photocutaneous disease in which subnormal activity of uroporphyrinogen decarboxylase is observed both in the liver and red cells. Hepatic iron plays a key role in the genesis of overt biochemical and clinical PCT. In this report, we have studied the properties of 10 000-fold purified erythrocyte uroporphyrinogen decarboxylase preparations from two familial PCT patients and a non-porphyric control subject. The apparent Michaelis constants (Km), determined by using uroporphyrinogen III substrate, were approx. 3.2-times higher for the enzyme from the diseased subjects (Km = approximately 1.0 microM) as compared to the normal (Km = 0.3 microM). Though both abnormal and normal enzymes were inhibited progressively with increasing concentrations of iron, the enzymes from diseased subjects exhibited greater susceptibility e.g. 0.1 mM Fe2+ inhibited the former about 50% and the latter about 20%. These observations suggest that the inherent biochemical defect in PCT is the reduced enzyme-substrate affinity and the intrinsic abnormal conformation renders the PCT enzyme particularly susceptible to inhibition by iron.
mesh_terms: D002262:Carboxy-Lyases / Q000097:blood*; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D011164:Porphyrias / Q000201:enzymology / Q000209:etiology*; D012871:Skin Diseases / Q000201:enzymology / Q000209:etiology*; D014575:Uroporphyrinogen Decarboxylase / Q000097:blood*
chemical_list: D007501:Iron; D002262:Carboxy-Lyases; D014575:Uroporphyrinogen Decarboxylase