α-Ketoglutarate dehydrogenase: a mitochondrial redox sensor.
α-Ketoglutarate dehydrogenase: a mitochondrial redox sensor.
复制标题
DOI：
10.3109/10715762.2010.534163
复制
发表时间：
2011-01
影响因子：
3.3
通讯作者：
Szweda LI
中科院分区：
文献类型：
--
作者：
McLain AL;Szweda PA;Szweda LI
α-酮戊二酸脱氢酶（KGDH）是Krebs循环中的关键调控酶，对线粒体氧化还原状态敏感。用H2O2处理线粒体，由于硫辛酸的谷胱甘肽化，导致KGDH的可逆抑制。在H2O2的消耗下，谷胱甘肽被谷氨酰胺还蛋白除去，恢复KGDH活性。谷胱甘肽化似乎是酶催化或需要一个独特的微环境。这可能是一种抗氧化反应，减少电子流向呼吸链，保护巯基残基免受氧化损伤。然而，KGDH也容易受到氧化损伤。4-羟基-2-壬烯醛（HNE），一种脂质过氧化产物，与硫辛酸反应导致酶失活。有证据表明，HNE修饰的硫辛酸是从KGDH中切割出来的，这可能是修复过程的第一步。因此，KGDH可能是一种氧化还原传感器，可逆地改变代谢以减少氧化损伤，并且在严重的氧化应激下，充当线粒体活力的哨兵。
α-Ketoglutarate dehydrogenase (KGDH), a key regulatory enzyme within the Krebs cycle, is sensitive to mitochondrial redox status. Treatment of mitochondria with H2O2 results in reversible inhibition of KGDH due to glutathionylation of the cofactor, lipoic acid. Upon consumption of H2O2, glutathione is removed by glutaredoxin restoring KGDH activity. Glutathionylation appears to be enzymatically catalysed or require a unique microenvironment. This may represent an antioxidant response, diminishing the flow of electrons to the respiratory chain and protecting sulphydryl residues from oxidative damage. KGDH is, however, also susceptible to oxidative damage. 4-Hydroxy-2-nonenal (HNE), a lipid peroxidation product, reacts with lipoic acid resulting in enzyme inactivation. Evidence indicates that HNE modified lipoic acid is cleaved from KGDH, potentially the first step of a repair process. KGDH is therefore a likely redox sensor, reversibly altering metabolism to reduce oxidative damage and, under severe oxidative stress, acting as a sentinel of mitochondrial viability.
登录
查看更多内容
影响因子：
2.9
作者：
Bulteau, AL;Ikeda-Saito, M;Szweda, LI
通讯作者：
Szweda, LI
影响因子：
4.7
作者：
Ambrus, Attila;Tretter, Laszlo;Adam-Vizi, Vera
通讯作者：
Adam-Vizi, Vera
DOI：
10.1046/j.1432-1033.2002.03204.x
发表时间：
2002-10-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Bunik, VI;Sievers, C
通讯作者：
Sievers, C
影响因子：
2.9
作者：
Cicchillo, RM;Iwig, DF;Booker, SJ
通讯作者：
Booker, SJ
影响因子：
7.4
作者：
Cadenas, E;Davies, KJA
通讯作者：
Davies, KJA