A potential biochemical explanation for the genesis of porphyria cutanea tarda

FEBS Letters

Pimstone, N.R.¹  Tan, K.T.¹  Mukerji, S.K.¹ 

[1] Department of Internal Medicine, Division of Gastroenterology, School of Medicine, University of California, Davis, 4301 X Street, Sacramento, CA 95817, USA

关键词: Porphyria cutanea tarda;    Uroporphyrinogen decarboxylase;    Human disease;    Erythrocyte;    Porphyrin;    Intracellular iron;   

DOI  :  10.1016/0014-5793(85)81026-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Fe²⁺ 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.

【 授权许可】

Unknown