α-酮戊二酸脱氢酶：氧化应激的靶点与产生源
Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress.
作者信息
Tretter Laszlo, Adam-Vizi Vera
机构信息
Semmelweis University and Neurobiochemical Group, Hungarian Academy of Sciences Department of Medical Biochemistry, Szentagothai Janos Knowledge Center PO Box 262, Budapest 1444, Hungary.
出版信息
Philos Trans R Soc Lond B Biol Sci. 2005 Dec 29;360(1464):2335-45. doi: 10.1098/rstb.2005.1764.
Alpha-ketoglutarate dehydrogenase (alpha-KGDH) is a highly regulated enzyme, which could determine the metabolic flux through the Krebs cycle. It catalyses the conversion of alpha-ketoglutarate to succinyl-CoA and produces NADH directly providing electrons for the respiratory chain. alpha-KGDH is sensitive to reactive oxygen species (ROS) and inhibition of this enzyme could be critical in the metabolic deficiency induced by oxidative stress. Aconitase in the Krebs cycle is more vulnerable than alpha-KGDH to ROS but as long as alpha-KGDH is functional NADH generation in the Krebs cycle is maintained. NADH supply to the respiratory chain is limited only when alpha-KGDH is also inhibited by ROS. In addition being a key target, alpha-KGDH is able to generate ROS during its catalytic function, which is regulated by the NADH/NAD+ ratio. The pathological relevance of these two features of alpha-KGDH is discussed in this review, particularly in relation to neurodegeneration, as an impaired function of this enzyme has been found to be characteristic for several neurodegenerative diseases.
α-酮戊二酸脱氢酶（α-KGDH）是一种受到高度调控的酶，它能够决定通过三羧酸循环的代谢通量。它催化α-酮戊二酸转化为琥珀酰辅酶A，并直接产生NADH为呼吸链提供电子。α-KGDH对活性氧（ROS）敏感，抑制该酶可能在氧化应激诱导的代谢缺陷中起关键作用。三羧酸循环中的乌头酸酶比α-KGDH更容易受到ROS的影响，但只要α-KGDH功能正常，三羧酸循环中的NADH生成就能维持。只有当α-KGDH也受到ROS抑制时，呼吸链的NADH供应才会受到限制。此外，作为一个关键靶点，α-KGDH在其催化功能过程中能够产生活性氧，这受NADH/NAD⁺比值的调节。本综述讨论了α-KGDH这两个特性的病理相关性，特别是与神经退行性变相关，因为已发现该酶功能受损是几种神经退行性疾病的特征。
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