Inhibition of human mitochondrial aldehyde dehydrogenase by 4-hydroxynon-2-enal and 4-oxonon-2-enal
Inhibition of human mitochondrial aldehyde dehydrogenase by 4-hydroxynon-2-enal and 4-oxonon-2-enal
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DOI：
10.1021/tx0501839
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发表时间：
2006-01-01
影响因子：
4.1
通讯作者：
Petersen, DR
中科院分区：
文献类型：
--
作者：
Doorn, JA;Hurley, TD;Petersen, DR
以往的研究发现脂质过氧化产物4-羟基壬-2-烯醛（4 HNE）是线粒体醛脱氢酶（ALDH 2）的底物和抑制剂。4 HNE对酶的抑制在动力学上被证明在低微摩尔醛下是可逆的，但在较高浓度下可能涉及共价修饰。脂质过氧化产物4-oxonon-2-enal（4 ONE）在结构上与4 HNE类似，它对蛋白质亲核试剂的反应性比4 HNE更强。本工作的目的是确定4 ONE是否是人ALDH 2（hALDH 2）的底物或抑制剂，并阐明4 HNE和4 ONE抑制酶的机制。发现4 ONE及其谷胱甘肽缀合物在NAD存在下都是酶的底物。04 - 04高密度聚乙烯（
Previous studies found the lipid peroxidation product 4-hydroxynon-2-enal (4HNE) to be both a substrate and an inhibitor of mitochondrial aldehyde dehydrogenase (ALDH2). Inhibition of the enzyme by 4HNE was demonstrated kinetically to be reversible at low micromolar aldehyde but may involve covalent modification at higher concentrations. Structurally analogous to 4HNE is the lipid peroxidation product 4-oxonon-2-enal (4ONE), which is more reactive than 4HNE toward protein nucleophiles. The goal of this work was to determine whether 4ONE is a substrate or inhibitor of human ALDH2 (hALDH2) and elucidate the mechanism of enzyme inhibition by 4HNE and 4ONE. Both 4ONE and its glutathione conjugate were found to be substrates for the enzyme in the presence of NAD. At low concentrations of 4ONE (