Sperringer Justin E, Addington Adele, Hutson Susan M
Department of Human Nutrition, Foods, and Exercise, Virginia Polytechnic Institute and State University, Integrated Life Sciences Building (0913), 1981 Kraft Drive, Blacksburg, VA, 24060, USA.
Neurochem Res. 2017 Jun;42(6):1697-1709. doi: 10.1007/s11064-017-2261-5. Epub 2017 Apr 18.
This review aims to provide a historical reference of branched-chain amino acid (BCAA) metabolism and provide a link between peripheral and central nervous system (CNS) metabolism of BCAAs. Leucine, isoleucine, and valine (Leu, Ile, and Val) are unlike most other essential amino acids (AA), being transaminated initially in extrahepatic tissues, and requiring interorgan or intertissue shuttling for complete catabolism. Within the periphery, BCAAs are essential AAs and are required for protein synthesis, and are key nitrogen donors in the form of Glu, Gln, and Ala. Leucine is an activator of the mammalian (or mechanistic) target of rapamycin, the master regulator of cell growth and proliferation. The tissue distribution and activity of the catabolic enzymes in the peripheral tissues as well as neurological effects in Maple Syrup Urine Disease (MSUD) show the BCAAs have a role in the CNS. Interestingly, there are significant differences between murine and human CNS enzyme distribution and activities. In the CNS, BCAAs have roles in neurotransmitter synthesis, protein synthesis, food intake regulation, and are implicated in diseases. MSUD is the most prolific disease associated with BCAA metabolism, affecting the branched-chain α-keto acid dehydrogenase complex (BCKDC). Mutations in the branched-chain aminotransferases (BCATs) and the kinase for BCKDC also result in neurological dysfunction. However, there are many questions of BCAA metabolism in the CNS (as well as the periphery) that remain elusive. We discuss areas of BCAA and BCKA metabolism that have yet to be researched adequately.
本综述旨在提供支链氨基酸（BCAA）代谢的历史参考，并建立外周和中枢神经系统（CNS）中BCAAs代谢之间的联系。亮氨酸、异亮氨酸和缬氨酸（Leu、Ile和Val）与大多数其他必需氨基酸不同，它们最初在肝外组织中进行转氨作用，并且需要器官间或组织间穿梭才能完成分解代谢。在外周，BCAAs是必需氨基酸，是蛋白质合成所必需的，并且是以Glu、Gln和Ala形式存在的关键氮供体。亮氨酸是雷帕霉素的哺乳动物（或机制性）靶点的激活剂，是细胞生长和增殖的主要调节因子。外周组织中分解代谢酶的组织分布和活性以及枫糖尿症（MSUD）中的神经学效应表明BCAAs在中枢神经系统中发挥作用。有趣的是，小鼠和人类中枢神经系统酶的分布和活性存在显著差异。在中枢神经系统中，BCAAs在神经递质合成、蛋白质合成、食物摄入调节中发挥作用，并与疾病有关。MSUD是与BCAA代谢相关的最常见疾病，影响支链α-酮酸脱氢酶复合体（BCKDC）。支链氨基转移酶（BCATs）和BCKDC激酶的突变也会导致神经功能障碍。然而，中枢神经系统（以及外周）中BCAA代谢仍有许多问题难以捉摸。我们讨论了BCAA和BCKA代谢中尚未得到充分研究的领域。
