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[2-氧代戊二酸脱氢酶复合体及其多点调控]

[2-Oxoglutarate dehydrogenase complex and its multipoint control].

作者信息

Tylicki Adam, Bunik Victoria I, Strumiło Sławomir

机构信息

Zakład Cytobiochemii, Instytut Biologii, Uniwersytet w Białymstoku, Białystok.

出版信息

Postepy Biochem. 2011;57(3):304-13.

Abstract

Enzymes control the course of biochemical reactions. The enzymes involved in bioenergetic processes play most important role in cell metabolism. One of them is 2-oxoglutarate dehydrogenase complex (OGDHC), the key regulatory enzyme of Krebs cycle. Krebs cycle integrates basic metabolic pathways of carbohydrates, fatty acids and amino acids during catabolic as well as anabolic reactions. Due to the key position of OGDHC in mitochondrial metabolism, its activity is controlled by many factors. Allosteric regulation by positive effectors (ADP, Pi, Ca2+, Mn2+) of the complex is very important. These effectors strongly enhances affinity of the first component of OGDHC to 2-oxoglutarate. Moreover there are negative effectors (ATP, NADH, succinyl-CoA) which affect all three enzymes of the complex. Regulation of biosynthesis of individual components of the complex by activation or inactivation of genes expression is very important for proper OGDHC activity too. Activity of OGDHC also depends on posttranslational modifications of its components. All of this control processes maintain OGDHC activity on adequate level and prevent the complex against its excessive action.

摘要

酶控制着生物化学反应的进程。参与生物能量过程的酶在细胞代谢中发挥着最重要的作用。其中之一是2-氧代戊二酸脱氢酶复合体(OGDHC),它是三羧酸循环的关键调节酶。三羧酸循环在分解代谢和合成代谢反应过程中整合了碳水化合物、脂肪酸和氨基酸的基本代谢途径。由于OGDHC在线粒体代谢中的关键地位,其活性受多种因素控制。复合体的正效应物(ADP、Pi、Ca2+、Mn2+)的变构调节非常重要。这些效应物强烈增强了OGDHC第一个组分对2-氧代戊二酸的亲和力。此外,还有负效应物(ATP、NADH、琥珀酰辅酶A),它们影响复合体的所有三种酶。通过基因表达的激活或失活来调节复合体各个组分的生物合成,对OGDHC的正常活性也非常重要。OGDHC的活性还取决于其组分的翻译后修饰。所有这些控制过程将OGDHC的活性维持在适当水平,并防止复合体过度作用。

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