Post-translational modifications of mitochondrial aldehyde dehydrogenase and biomedical implications.
Post-translational modifications of mitochondrial aldehyde dehydrogenase and biomedical implications.
复制标题
DOI：
10.1016/j.jprot.2011.05.013
复制
发表时间：
2011-11-18
影响因子：
3.3
通讯作者：
Moon KH
中科院分区：
文献类型：
--
作者：
Song BJ;Abdelmegeed MA;Yoo SH;Kim BJ;Jo SA;Jo I;Moon KH
乙醛脱氢酶（ALDH）是NAD（P）+依赖性脱氢酶的大家族成员，负责许多内源性和外源性醛到相应酸的不可逆代谢。在19种ALDH同工酶中，线粒体ALDH 2是一种低Km酶，负责乙醛和脂质过氧化物如丙二醛和4-羟基壬烯醛的代谢，这两种酶都是高度反应性和毒性的。因此，ALDH 2的抑制将导致乙醇摄入和/或暴露于有毒化学品后乙醛和其他反应性脂质过氧化物水平升高。此外，许多在ALDH 2基因中具有显性负突变的东亚人具有降低的ALDH 2活性，增加了各种类型的癌症、心肌梗死、酒精性肝病和其他病理状况的风险。本文以线粒体ALDH 2为例，简要介绍了其在接触有毒化学物质后或不同疾病状态下的多种翻译后修饰及其在促进酒精/药物介导的组织损伤中的病理生理作用。我们还简要地提到了令人兴奋的临床前转化研究机会，以确定ALDH 2及其同工酶的小分子激活剂作为潜在的治疗/预防剂，以对抗ALDH酶的表达或活性被改变或失活的各种疾病状态。
Aldehyde dehydrogenases (ALDHs) represent large family members of NAD(P)+-dependent dehydrogenases responsible for the irreversible metabolism of many endogenous and exogenous aldehydes to the corresponding acids. Among 19 ALDH isozymes, mitochondrial ALDH2 is a low Km enzyme responsible for the metabolism of acetaldehyde and lipid peroxides such as malondialdehyde and 4-hydroxynonenal, both of which are highly reactive and toxic. Consequently, inhibition of ALDH2 would lead to elevated levels of acetaldehyde and other reactive lipid peroxides following ethanol intake and/or exposure to toxic chemicals. In addition, many East Asian people with a dominant negative mutation in ALDH2 gene possess a decreased ALDH2 activity with increased risks for various types of cancer, myocardial infarct, alcoholic liver disease, and other pathological conditions. The aim of this review is to briefly describe the multiple post-translational modifications of mitochondrial ALDH2, as an example, after exposure to toxic chemicals or under different disease states and their pathophysiological roles in promoting alcohol/drug-mediated tissue damage. We also briefly mention exciting preclinical translational research opportunities to identify small molecule activators of ALDH2 and its isozymes as potentially therapeutic/preventive agents against various disease states where the expression or activity of ALDH enzymes is altered or inactivated.
登录
查看更多内容
影响因子：
2.3
作者：
DeMaster, EG;Redfern, B;Nagasawa, HT
通讯作者：
Nagasawa, HT
影响因子：
5
作者：
Churchill, Eric N.;Disatnik, Marie-Helene;Mochly-Rosen, Daria
通讯作者：
Mochly-Rosen, Daria
影响因子：
15.8
作者：
Brooks PJ;Enoch MA;Goldman D;Li TK;Yokoyama A
通讯作者：
Yokoyama A
影响因子：
2.6
作者：
Black WJ;Stagos D;Marchitti SA;Nebert DW;Tipton KF;Bairoch A;Vasiliou V
通讯作者：
Vasiliou V
影响因子：
3.6
作者：
Bae, MA;Song, BJ
通讯作者：
Song, BJ