The last decade saw major advances in understanding the metabolism of Coenzyme A (CoA) thioesters (acyl-CoAs) and related inborn errors (CoA metabolic diseases, CAMDs). For diagnosis, acylcarnitines and organic acids, both derived from acyl-CoAs, are excellent markers of most CAMDs. Clinically, each CAMD is unique but strikingly, three main patterns emerge: first, systemic decompensations with combinations of acidosis, ketosis, hypoglycemia, hyperammonemia and fatty liver; second, neurological episodes, particularly acute "stroke-like" episodes, often involving the basal ganglia but sometimes cerebral cortex, brainstem or optic nerves and third, especially in CAMDs of long chain fatty acyl-CoA metabolism, lipid myopathy, cardiomyopathy and arrhythmia. Some patients develop signs from more than one category. The pathophysiology of CAMDs is not precisely understood. Available data suggest that signs may result from CoA sequestration, toxicity and redistribution (CASTOR) in the mitochondrial matrix has been suggested to play a role. This predicts that most CAMDs cause deficiency of CoA, limiting mitochondrial energy production, and that toxic effects from the abnormal accumulation of acyl-CoAs and from extramitochondrial functions of acetyl-CoA may also contribute. Recent progress includes the following. (1) Direct measurements of tissue acyl-CoAs in mammalian models of CAMDs have been related to clinical features. (2) Inborn errors of CoA biosynthesis were shown to cause clinical changes similar to those of inborn errors of acyl-CoA degradation. (3) CoA levels in cells can be influenced pharmacologically. (4) Roles for acetyl-CoA are increasingly identified in all cell compartments. (5) Nonenzymatic acyl-CoA-mediated acylation of intracellular proteins occurs in mammalian tissues and is increased in CAMDs.

中文翻译：

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线粒体酰基辅酶a代谢的先天性错误：酰基辅酶A生物学符合临床要求。

在过去的十年中，在理解辅酶A（CoA）硫酯（酰基-CoA）的代谢以及相关的先天性错误（CoA代谢病，CAMD）方面取得了重大进展。为了诊断，酰基肉碱和有机酸均来源于酰基辅酶A，是大多数CAMD的出色标记。在临床上，每种CAMD都是独特的，但引人注目的是，出现了三种主要模式：首先，全身性代偿失调伴酸中毒，酮症，低血糖，高氨血症和脂肪肝。第二，神经系统发作，特别是急性的“中风样”发作，通常累及基底神经节，但有时累及大脑皮层，脑干或视神经，第三，尤其是在长链脂肪酰基辅酶A代谢，脂质肌病，心肌病和心律不齐的CAMD中。一些患者出现了不止一种类别的体征。CAMDs的病理生理学尚不明确。现有数据表明，迹象表明线粒体基质中的CoA螯合，毒性和再分布（CASTOR）可能导致了这种现象。这表明大多数CAMD会导致CoA缺乏，限制线粒体能量的产生，并且酰基辅酶A异常积累和乙酰辅酶A的线粒体功能也可能会产生毒性作用。最近的进展包括以下方面。（1）在CAMDs哺乳动物模型中直接测量组织酰基CoA与临床特征有关。（2）已证明CoA生物合成的先天性错误会导致临床变化，类似于酰基CoA降解的先天性错误。（3）细胞中的CoA水平可能在药理上受到影响。（4）在所有细胞区室中，乙酰辅酶A的作用越来越多。（5）非酶酰基辅酶A介导的细胞内蛋白酰化作用发生在哺乳动物组织中，并在CAMDs中增加。