6 Branched Chain Amino Acids (BCAAs) in Brain
The branched chain amino acids (BCAAs) play a role in glutamate neurotransmitter synthesis by providing a ferry system to move nitrogen between astrocytes and neurons for the synthesis of glutamate. This hypothetical nitrogen cycle, the branched chain ami
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Branched Chain Amino Acids (BCAAs) in Brain
S. M. Hutson . A. J. Sweatt . K. F. LaNoue
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Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
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Branched Chain Amino Acid Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
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Branched Chain Amino Acids Are Nitrogen Donors in Peripheral Tissues . . . . . . . . . . . . . . . . . . . . 121
4 Branched Chain Amino Acids as Nitrogen Donors in the Central Nervous System . . . . . . . . . . . 121 4.1 Intercellular Nitrogen Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 5
Role of BCAA in de novo Glutamate Synthesis and the Branched Chain Aminotransferase (BCAT) Cycle Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
6 Localization of BCAA Catabolic Enzymes in Rodent Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 6.1 The Cytosolic BCATc Isozyme . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 6.2 The Mitochondrial Enzymes BCATm and Branched Chain a-Keto Acid Dehydrogenase (BCKD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 6.3 The BCAT Cycle and GABA Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 7
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Conclusions, Implications for Disorders of BCAA Metabolism, and Future Directions . . . . . . . . 127
Springer-Verlag Berlin Heidelberg 2007
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Branched chain amino acids (BCAAs) in brain
Abstract: The branched chain amino acids (BCAAs) play a role in glutamate neurotransmitter synthesis by providing a ferry system to move nitrogen between astrocytes and neurons for the synthesis of glutamate. This hypothetical nitrogen cycle, the branched chain aminotransferase (BCAT) cycle, is tied to the glutamate/glutamine cycle and is an arm of the glutamate/pyruvate cycle. Immunolocalization of the BCAT isozymes in rodent brain shows that the cytosolic BCATc is localized in selected glutamatergic and GABAergic neurons whereas the mitochondrial isozyme, BCATm, is found in astroglia. These results provide support for the cycle hypothesis and suggest BCAA also play a role in g‐aminobutyric acid (GABA) metabolism. When the BCAA catabolic disposal system is genetically impaired in humans, serum BCAA and BCKA levels rise and severe neurological dysfunction occurs. In the hereditary metabolic disease that results from mutations in the branched chain a‐keto acid dehydrogenase complex (BCKD), maple syrup urine disease, the most obvious symptom
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