Department of Medical Biochemistry, Semmelweis University, Laboratory of Neurobiochemistry, Hungarian Academy of Sciences, Budapest, Hungary.
Neurochem Int. 2013 Apr;62(5):757-63. doi: 10.1016/j.neuint.2013.01.012. Epub 2013 Jan 26.
In addition to complexes in the respiratory chain, few dehydrogenases playing key roles in the physiological metabolism in neurons, are able to generate reactive oxygen species (ROS) in mitochondria. One of them is the Krebs cycle enzyme, α-ketoglutarate dehydrogenase (α-KGDH), which is capable of producing superoxide and hydrogen peroxide by the E3 subunit of the enzyme regulated by changes in the NADH/NAD(+) ratio. Mutations in the E3 subunit known to be related to diseases in humans were shown to have increased ROS-forming ability. α-Glycerophosphate dehydrogenase (α-GPDH) located on the outer surface of the inner membrane can also generate ROS, which is stimulated by Ca(2+). ROS production by α-GPDH is unique as it does not require Ca(2+) uptake and it is observed in respiring as well as damaged, bioenergetically incompetent mitochondria. The possible role of ROS generation by these dehydrogenases in brain pathology is discussed in this review.
除了呼吸链复合物外，神经元中生理代谢起关键作用的少数脱氢酶也能够在线粒体中产生活性氧（ROS）。其中之一是三羧酸循环酶α-酮戊二酸脱氢酶（α-KGDH），其通过受 NADH/NAD（+）比例变化调节的酶的 E3 亚基产生超氧阴离子和过氧化氢。已知与人类疾病相关的 E3 亚基突变显示出增强的 ROS 形成能力。位于内膜外表面的α-甘油磷酸脱氢酶（α-GPDH）也可以产生 ROS，其受到 Ca（2+）的刺激。α-GPDH 产生 ROS 的特点是不需要 Ca（2+）摄取，并且在呼吸以及生物能量功能失调的线粒体中都观察到。本文综述了这些脱氢酶产生 ROS 在脑病理学中的可能作用。
