Lipoic acid metabolism and mitochondrial redox regulation

被引：321

作者：

Solmonson, Ashley ^{[1
]}

DeBerardinis, Ralph J. ^{[1
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Childrens Med Ctr Res Inst, 5323 Harry Hines Blvd, Dallas, TX 75390 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2018年 / 293卷 / 20期

关键词：

ALPHA-KETOGLUTARATE DEHYDROGENASE; LIPOATE-PROTEIN LIGASE; IRON-SULFUR CLUSTER; ESCHERICHIA-COLI; SUPEROXIDE/HYDROGEN PEROXIDE; POSTTRANSLATIONAL MODIFICATION; LIPOAMIDE DEHYDROGENASE; S-GLUTATHIONYLATION; MOLECULAR-CLONING; CARRIER PROTEIN;

D O I：

10.1074/jbc.TM117.000259

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Lipoic acid is an essential cofactor for mitochondrial metabolism and is synthesized de novo using intermediates from mitochondrial fatty-acid synthesis type II, S-adenosylmethionine and iron-sulfur clusters. This cofactor is required for catalysis by multiple mitochondrial 2-ketoacid dehydrogenase complexes, including pyruvate dehydrogenase, -ketoglutarate dehydrogenase, and branched-chain ketoacid dehydrogenase. Lipoic acid also plays a critical role in stabilizing and regulating these multienzyme complexes. Many of these dehydrogenases are regulated by reactive oxygen species, mediated through the disulfide bond of the prosthetic lipoyl moiety. Collectively, its functions explain why lipoic acid is required for cell growth, mitochondrial activity, and coordination of fuel metabolism.

引用

页码：7522 / 7530

页数：9

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