过氧化物酶体增殖剂和降血脂药对线粒体内膜相关D-3-羟基丁酸脱氢酶（BDH）的影响。

Effect of peroxisomes proliferators and hypolipemic agents on mitochondrial inner membrane linked D-3-hydroxybutyrate dehydrogenase (BDH).

el Kebbaj M H, Cherkaoui Malki M, Latruffe N

LBMC, University of Burgundy, Dijon, France.

Biochem Mol Biol Int. 1995 Jan;35(1):65-77.

Abstract

D-3-hydroxybutyrate dehydrogenase EC 1.1.1.30 (BDH) activity was measured in mitochondria of rats submitted to an intermittent feeding treatment with ciprofibrate or fenofibrate, i.e. fibrate analogues with hypolipemic activity and peroxisome proliferation properties. Our data shows an inhibition of rat liver mitochondrial BDH activity. This inhibitory effect is abolished when the treatment is stopped and reappears after a second treatment. 2. Incubation of hypolipemic agents (ciprofibrate, clofibrate, clobuzarit, fenofibrate or 2,4 dichlorophenoxyacetic acid) with submitochondrial linked BDH leads to an inhibition in a concentration dependent manner. 3. The protection by NAD(H) (coenzymes) and by methyl-malonate (a substrate analogue and competitive inhibitor) indicates that the inhibition occurs in the active site. On the other hand, there is a strong protection by phospholipid vesicles. This trapping effect may be attributed to lipophilic properties of hypolipemic agents. 4. Comparative effect of hypolipemic agents on mitochondrial BDH activity from rat liver and from Tetrahymena pyriformis indicates the same inhibition and same protection effects. This supports conservation of the enzymatic properties according to the evolution.

摘要

用环丙贝特或非诺贝特（即具有降血脂活性和过氧化物酶体增殖特性的贝特类似物）对大鼠进行间歇性喂食处理后，测定其线粒体中D - 3 - 羟基丁酸脱氢酶（EC 1.1.1.30，BDH）的活性。我们的数据显示大鼠肝脏线粒体BDH活性受到抑制。当停止处理时，这种抑制作用消失，再次处理后又会出现。2. 将降血脂药物（环丙贝特、氯贝丁酯、氯布扎利特、非诺贝特或2,4 - 二氯苯氧乙酸）与亚线粒体连接的BDH一起孵育会导致浓度依赖性抑制。3. NAD(H)（辅酶）和甲基丙二酸（一种底物类似物和竞争性抑制剂）的保护作用表明抑制发生在活性位点。另一方面，磷脂囊泡有很强的保护作用。这种捕获效应可能归因于降血脂药物的亲脂性。4. 降血脂药物对大鼠肝脏和梨形四膜虫线粒体BDH活性的比较效应表明存在相同的抑制和相同的保护作用。这支持了酶特性根据进化而保守的观点。