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Branched-Chain Amino Acids and Brain Metabolism
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Journal Article
Branched-Chain Amino Acids and Brain Metabolism
2017
Overview
This review aims to provide a historical reference of branched-chain amino acid (BCAA) metabolism and provide a link between peripheral and central nervous system (CNS) metabolism of BCAAs.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.
Publisher
Springer US,Springer Nature B.V
Subject
/ Amino Acids, Branched-Chain - genetics
/ Amino Acids, Branched-Chain - metabolism
/ Animals
/ Biomedical and Life Sciences
/ Brain
/ Branched-chain-amino-acid transaminase
/ Chains
/ Enzymes
/ Genes
/ Humans
/ Kinases
/ Leucine
/ Maple Syrup Urine Disease - genetics
/ Maple Syrup Urine Disease - metabolism
/ Nitrogen
/ Proteins
/ Signal Transduction - physiology
/ Tissues
/ Urine
/ Valine
