Interindividual variations in the activities of cytosolic and microsomal epoxide hydrolase in human liver.
Interindividual variations in the activities of cytosolic and microsomal epoxide hydrolase in human liver.
复制标题
人肝脏中胞质和微粒体环氧化物水解酶活性的个体差异。
作者：
I. Mertes;R. Fleischmann;H. Glatt;F. Oesch
哺乳动物体内至少存在两种在药物代谢中具有广泛意义的环氧化物水解酶。一种酶位于内质网和其他膜（EHm）中，另一种酶位于胞质溶胶（EHc）中。在本研究中，我们发现，人类在肝脏中的这些酶的活性差异很大。用苯并[a]芘4，5-氧化物作为底物测定的166名受试者（其中大多数为肝病患者）微粒体中的比活度变化为63倍。在细胞质中的活动，确定与反式二苯乙烯氧化物作为底物之间的变化539倍，135名受试者。细分为不同的诊断组显示EHm活性增加（对照组的1.7倍），但EHc活性在结核病患者利福平，乙胺丁醇和异烟肼治疗。没有其他诊断组显示EH活动显着改变。此外，这些活动在女性和男性、酗酒者和非酗酒者或吸烟者和非吸烟者之间没有差异。在测定EHc和EHm活性的77个受试者中，未观察到它们之间的相关性，表明单独的生物控制。
Mammals have at least two epoxide hydrolases (EHs) with a broad significance in drug metabolism. One enzyme is localized in the endoplasmic reticulum and other membranes (EHm), and the other is in the cytosol (EHc). In the present study we found that humans differ greatly in the activities of these enzymes in liver. The specific activities in microsomes from 166 subjects (most of them patients suffering from hepatic diseases), measured with benzo[a]pyrene 4,5-oxide as the substrate, varied by a factor of 63. The activities in the cytosol, determined with trans-stilbene oxide as substrate varied 539-fold among 135 subjects. A subdivision into different diagnostic groups showed an increase in EHm activity (1.7-fold control) but not EHc activity in tuberculosis patients treated with rifampicin, ethambutol and isoniazid. No other diagnostic group showed significantly altered EH activities. Furthermore the activities did not differ between females and males, alcoholics and non-alcoholics or smokers and non-smokers. In the 77 subjects where both EHc and EHm activities were determined, no correlation between them was observed, indicating separate biological control.