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酮戊二酸脱氢酶复合体

酮戊二酸脱氢酶复合体(英語:oxoglutarate dehydrogenase complex,缩写OGDC;或稱英語:α-ketoglutarate dehydrogenase complex)是一个复合酶,因其在三羧酸循环中的作用而众所周知。

单位

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丙酮酸脱氢酶复合体(PDC)十分相似,此酶由三个组件形成一个复合体:

单位 EC编号 名称 基因 辅酶
E1 EC 1.2.4.2 酮戊二酸脱氢酶 OGDH 硫胺素焦磷酸
E2 EC 2.3.1.61 二氢硫辛酰琥珀酰转移酶 DLST 硫辛酸
E3 EC 1.8.1.4 二氢硫辛酰脱氢酶 DLD 黄素腺嘌呤二核苷酸

事实上,生物学家已经将类似的多酶复合体表征并分成三大类,一类是专门作用于丙酮酸,第二类专门作用于α-酮戊二酸,第三类专门作用于支链α-酮酸。

特性

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代谢途径

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此酶参与三种不同的代谢途径

动力学特性

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下列酶参数的值源自棕色固氮菌 (1):

  • KM: 0.14 ± 0.04 mM
  • Vmax : 9 ± 3 μmol.min-1.mg-1

三羧酸循环

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反应

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在三羧酸循环中此酶催化的反应为:

α-酮戊二酸 + NAD+ + 辅酶A琥珀酰辅酶A + 二氧化碳 + NADH
酮戊二酸脱氢酶(α-酮戊二酸脱氢酶)

进行此反应需要以下三步骤:

此反应的ΔG°'为-7.2 千卡/摩尔。此氧化过程所需的能量以硫酯键的形式被保存在琥珀酰辅酶A之中。

调控

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酮戊二酸脱氢酶是三羧酸循环中的一个关键调控点。此酶被其产物琥珀酰辅酶ANADH所抑制。细胞中所充斥的能量高亦是抑制因素。二磷酸腺苷与钙离子是酶的变构增活因子。

病理学

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α-酮戊二酸脱氢酶是原发性胆汁性肝硬变中的自身抗原,这是一种急性肝脏衰竭。由此所产生的抗体似乎专门识别那些由炎症免疫反应所导致的被氧化的蛋白质。这类炎症反应中的一些可被解释为谷蛋白过敏[1]。其他的线粒体自身抗原包括了丙酮酸脱氢酶与支链α-酮酸脱氢酶复合体,这些自身抗原可被抗线粒体抗体所识别。在许多神经变性疾病期间,α-酮戊二酸脱氢酶复合体的活性会下降很多。

参考文献

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  1. ^ Leung PS, Rossaro L, Davis PA; et al. Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis. Hepatology. 2007, 46: 1436. PMID 17657817. doi:10.1002/hep.21828. 
  1. Bunik V, Westphal AH, de Kok A: Kinetic properties of the 2-oxoglutarate dehydrogenase complex from Azotobacter vinelandii evidence for the formation of a precatalytic complex with 2-oxoglutarate. Eur J Biochem 2000; 267(12): 3583-91. PMID 10848975.
  2. Bunik VI, Strumilo S: "Regulation of Catalysis Within Cellular Network: Metabolic and Signaling Implications of the 2-Oxoglutarate Oxidative Decarboxylation." Current Chemical Biology, 2009, 3: 279-290
  3. Bunik VI, Fernie AR: "Metabolic control exerted by the 2-oxoglutarate dehydrogenase reaction: a cross-kingdom comparison of the crossroad between energy production and nitrogen assimilation." Biochem. J. 2009, 422: 405–421
  4. L. Trofimova, M. Lovat, A. Groznaya, E. Efimova, T. Dunaeva, M. Maslova, A. Graf, and V. Bunik: "Behavioral Impact of the Regulation of the Brain 2-Oxoglutarate Dehydrogenase Complex by Synthetic Phosphonate Analog of 2-Oxoglutarate: Implications into the Role of the Complex in Neurodegenerative Diseases." International Journal of Alzheimer Disease 2010; Volume 2010, Article ID 749061, 8 pages, doi:10.4061/2010/749061, https://web.archive.org/web/20101218093532/http://www.sage-hindawi.com/journals/ijad/2010/749061.html

外部链接

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酮戊二酸脱氢酶复合体
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