A.N. Belozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA.
Biol Chem. 2018 Apr 25;399(5):407-420. doi: 10.1515/hsz-2017-0284.
Mitochondrial 2-oxoacid dehydrogenase complexes oxidize 2-oxoglutarate, pyruvate, branched-chain 2-oxoacids and 2-oxoadipate to the corresponding acyl-CoAs and reduce NAD+ to NADH. The isolated enzyme complexes generate superoxide anion radical or hydrogen peroxide in defined reactions by leaking electrons to oxygen. Studies using isolated mitochondria in media mimicking cytosol suggest that the 2-oxoacid dehydrogenase complexes contribute little to the production of superoxide or hydrogen peroxide relative to other mitochondrial sites at physiological steady states. However, the contributions may increase under pathological conditions, in accordance with the high maximum capacities of superoxide or hydrogen peroxide-generating reactions of the complexes, established in isolated mitochondria. We assess available data on the use of modulations of enzyme activity to infer superoxide or hydrogen peroxide production from particular 2-oxoacid dehydrogenase complexes in cells, and limitations of such methods to discriminate specific superoxide or hydrogen peroxide sources in vivo.
线粒体 2-氧代酸脱氢酶复合物将 2-氧代戊二酸、丙酮酸、支链 2-氧代酸和 2-氧代己二酸氧化为相应的酰基辅酶 A，并将 NAD+还原为 NADH。在特定反应中，分离的酶复合物通过将电子泄漏到氧气中而生成超氧阴离子自由基或过氧化氢。使用模拟细胞溶胶的介质中的分离线粒体进行的研究表明，与生理稳态下其他线粒体部位相比，2-氧代酸脱氢酶复合物对超氧或过氧化氢的产生贡献较小。然而，根据在分离的线粒体中建立的复合物的超氧或过氧化氢生成反应的高最大容量，这些贡献可能会在病理条件下增加。我们评估了可用的数据，这些数据使用酶活性的调节来推断来自细胞中特定 2-氧代酸脱氢酶复合物的超氧或过氧化氢的产生，并评估了这些方法在体内区分特定超氧或过氧化氢来源的局限性。
