Welbio and de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
J Inherit Metab Dis. 2013 May;36(3):427-34. doi: 10.1007/s10545-012-9571-1. Epub 2013 Jan 8.
Enzymes of intermediary metabolism are less specific than what is usually assumed: they often act on metabolites that are not their 'true' substrate, making abnormal metabolites that may be deleterious if they accumulate. Some of these abnormal metabolites are reconverted to normal metabolites by repair enzymes, which play therefore a role akin to the proofreading activities of DNA polymerases and aminoacyl-tRNA synthetases. An illustrative example of such repair enzymes is L-2-hydroxyglutarate dehydrogenase, which eliminates a metabolite abnormally made by a Krebs cycle enzyme. Mutations in L-2-hydroxyglutarate dehydrogenase lead to L-2-hydroxyglutaric aciduria, a leukoencephalopathy. Other examples are the epimerase and the ATP-dependent dehydratase that repair hydrated forms of NADH and NADPH; ethylmalonyl-CoA decarboxylase, which eliminates an abnormal metabolite formed by acetyl-CoA carboxylase, an enzyme of fatty acid synthesis; L-pipecolate oxidase, which repairs a metabolite formed by a side activity of an enzyme of L-proline biosynthesis. Metabolite proofreading enzymes are likely quite common, but most of them are still unidentified. A defect in these enzymes may account for new metabolic disorders.
它们经常作用于不是其“真正”底物的代谢物，从而产生异常的代谢物，如果它们积累，可能是有害的。这些异常代谢物中的一些被修复酶重新转化为正常代谢物，因此修复酶起着类似于 DNA 聚合酶和氨酰-tRNA 合成酶的校对活性的作用。此类修复酶的一个说明性示例是 L-2-羟戊二酸脱氢酶，它消除了克雷布斯循环酶异常产生的代谢物。L-2-羟戊二酸脱氢酶的突变导致 L-2-羟戊二酸尿症，一种白质脑病。其他示例是修复水化形式的 NADH 和 NADPH 的差向异构酶和 ATP 依赖性脱水酶；消除由脂肪酸合成酶乙酰辅酶 A 羧化酶形成的异常代谢物的乙基丙二酰辅酶 A 脱羧酶；修复由 L-脯氨酸生物合成酶的侧活性形成的代谢物的 L-哌可酸氧化酶。代谢物校对酶可能相当普遍，但其中大多数仍未被识别。这些酶的缺陷可能导致新的代谢紊乱。
