Acylcarnitines--old actors auditioning for new roles in metabolic physiology.
Acylcarnitines--old actors auditioning for new roles in metabolic physiology.
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DOI：
10.1038/nrendo.2015.129
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Adams SH
中科院分区：
文献类型：
--
作者：
McCoin CS;Knotts TA;Adams SH
代谢途径的扰动可导致长链酰基肉碱（lcac）血浆和组织浓度的显著增加。例如，在运动过程中，血液和肌肉中lcac和其他酰基肉碱的水平升高，因为酰基辅酶A组织池的变化反映了加速的燃料通量，而这种通量与线粒体能量需求和三羧酸循环能力不完全耦合。酰基肉碱生成和积累的自然起起伏伏与遗传性脂肪酸氧化障碍（FAODs）、心脏缺血或2型糖尿病形成鲜明对比。这些情况的特点是非常高（FAODs，缺血）或适度增加（2型糖尿病）组织和血液中的lcac水平。尽管特定的血浆LCAC浓度和链长被广泛用作FAODs的诊断指标，但对LCAC过量积累的潜在影响或酰基肉碱作为细胞代谢生理调节剂的作用的研究尚缺乏。然而，越来越多的证据强调了lcac对病理生理学不同方面的可能影响，如心肌缺血结局、胰岛素敏感性和炎症。因此，本综述旨在为代谢紊乱患者组织中LCACs积累的潜在后果提供一个理论框架。
Perturbations in metabolic pathways can cause substantial increases in plasma and tissue concentrations of long-chain acylcarnitines (LCACs). For example, the levels of LCACs and other acylcarnitines rise in the blood and muscle during exercise, as changes in tissue pools of acylcoenzyme A reflect accelerated fuel flux that is incompletely coupled to mitochondrial energy demand and capacity of the tricarboxylic acid cycle. This natural ebb and flow of acylcarnitine generation and accumulation contrasts with that of inherited fatty acid oxidation disorders (FAODs), cardiac ischaemia or type 2 diabetes mellitus. These conditions are characterized by very high (FAODs, ischaemia) or modestly increased (type 2 diabetes mellitus) tissue and blood levels of LCACs. Although specific plasma LCAC concentrations and chain-lengths are widely used as diagnostic markers of FAODs, research into the potential effects of excessive LCAC accumulation or the roles of acylcarnitines as physiological modulators of cell metabolism is lacking. Nevertheless, a growing body of evidence has highlighted possible effects of LCACs on disparate aspects of pathophysiology, such as cardiac ischaemia outcomes, insulin sensitivity and inflammation. This Review, therefore, aims to provide a theoretical framework for the potential consequences of tissue build-up of LCACs among persons with metabolic disorders.