Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie Medicine-New Brunswick, Dalhousie University, Saint John, New Brunswick, Canada.
FASEB J. 2019 Aug;33(8):8711-8731. doi: 10.1096/fj.201802842RR. Epub 2019 May 14.
Beyond their contribution as fundamental building blocks of life, branched-chain amino acids (BCAAs) play a critical role in physiologic and pathologic processes. Importantly, BCAAs are associated with insulin resistance, obesity, cardiovascular disease, and genetic disorders. However, several metabolome-wide studies in recent years could not attribute alterations in systemic BCAAs as the sole driver of endocrine perturbations, suggesting that a snapshot of global BCAA changes does not always reveal the underlying modifications. Because enzymes catabolizing BCAAs have a unique distribution, it is plausible that the tissue-specific roles of BCAA-catabolic enzymes could precipitate changes in systemic BCAA levels, flux, and action. We review the genetic and pharmacological approaches dissecting the role of BCAA-catabolic enzyme dysfunctions. We summarized emerging evidence on BCAA metabolic intermediates, tissue specificity of BCAA-catabolizing enzymes, and crosstalk between different metabolites in driving metabolic maladaptation in health and pathology. This review substantiates the understanding that tissue-specific dysfunction of the BCAA-catabolic enzymes and accumulating intermediary metabolites could act as better surrogates of metabolic imbalances, highlighting the biochemical communication among the nutrient triad of BCAAs, glucose, and fatty acid.-Biswas, D., Duffley, L., Pulinilkunnil, T. Role of branched-chain amino acid-catabolizing enzymes in intertissue signaling, metabolic remodeling, and energy homeostasis.
除了作为生命基本构建块的作用外，支链氨基酸（BCAAs）在生理和病理过程中也起着关键作用。重要的是，BCAAs 与胰岛素抵抗、肥胖、心血管疾病和遗传疾病有关。然而，近年来的几项代谢组学研究不能将系统 BCAAs 的变化归因于内分泌紊乱的唯一驱动因素，这表明全局 BCAAs 变化的快照并不总是揭示潜在的变化。由于分解 BCAAs 的酶具有独特的分布，因此可以合理地假设，BCAA 分解代谢酶的组织特异性作用可能会导致系统 BCAAs 水平、通量和作用发生变化。我们回顾了遗传和药理学方法来剖析 BCAA 分解代谢酶功能障碍的作用。我们总结了关于 BCAA 代谢中间产物、BCAA 分解代谢酶的组织特异性以及不同代谢物之间相互作用在健康和病理状态下驱动代谢适应不良的新出现的证据。这篇综述证实了这样一种理解，即 BCAA 分解代谢酶的组织特异性功能障碍和积累的中间代谢物可以作为代谢失衡的更好替代物，突出了 BCAAs、葡萄糖和脂肪酸这三大营养素之间的生化通讯。-Biswas，D.，Duffley，L.，Pulinilkunnil，T. 支链氨基酸分解代谢酶在组织间信号传递、代谢重塑和能量平衡中的作用。
