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A potential biochemical explanation for the genesis of porphyria cutanea tarda
Author(s) -
Mukerji S.K.,
Pimstone N.R.,
Tan K.T.
Publication year - 1985
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(85)81026-7
Subject(s) - uroporphyrinogen iii decarboxylase , porphyria cutanea tarda , enzyme , chemistry , porphyria , endocrinology , substrate (aquarium) , enzyme assay , medicine , biochemistry , heme , biology , ecology
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 10000‐fold purified erythrocyte uroporphyrinogen decarboxylase preparations from two familial PCT patients and a non‐porphyric control subject. The apparent Michaelis constants ( K m ), determined by using uroporphyrinogen III substrate, were approx. 3.2‐times higher for the enzyme from the diseased subjects ( K m = ~1.0 μM) as compared to the normal ( K m = 0.3 μM). 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 Fe 2+ inhibited the former about 50% and the latter about 20%. These observations suggest that (i) the inherent biochemical defect in PCT is the reduced enzyme‐substrate affinity and (ii) the intrinsic abnormal conformation renders the PCT enzyme particularly susceptible to inhibition by iron.