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6 Branched Chain Amino Acids (BCAAs) in Brain

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Handbook of Neurochemistry and Molecular Neurobiology

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 γ-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 α-keto acid dehydrogenase complex (BCKD), maple syrup urine disease, the most obvious symptoms are neurological. Useful animal models for the human condition are not yet available.

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Abbreviations

BCAA:

branched chain amino acid

BCAT:

branched chain aminotransferase

BCATc:

cytosolic branched chain aminotransferase

BCATm:

mitochondrial branched chain aminotransferase

BCKA:

branched chain α-keto acid

BCKD:

branched chain α-keto acid dehydrogenase

E1:

branched chain α-keto acid decarboxylase

E2:

dihydrolipoly transacylase

E3:

dihydrolipoyl dehydrogenase

GABA:

γ-aminobutyric acid

GABA-T, GABA:

aminotransferase

GAD:

glutamate decarboxylase

αKG:

α-ketoglutarate

KIC:

α-ketoisocaproate

KIV:

α-ketoisovalerate

KMV:

α-keto-β-methylvalerate

MSUD:

Maple Syrup Urine Disease

PC:

pyruvate carboxylase

TCA:

tricarboxylic acid

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Acknowledgments

The work reported here was supported by Grants NS-38641 and DK-34738 from the US National Institutes of Health.

Authors
  1. S. M. Hutson
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  2. A. J. Sweatt
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  3. K. F. LaNoue
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, New york, USA

    Abel Lajtha (Director) (Director)

  2. The Centre for Laboratory Medicine, Tampere University Hospital, PB 2000, FI-33520, Tampere, Finland

    Simo S. Oja

  3. Inst. for Pharmacology, Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen, Denmark

    Arne Schousboe

  4. Brain Research Center, Medical School, University of Tampere, FI-33014, Espoo, Finland

    Pirjo Saransaari

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Hutson, S.M., Sweatt, A.J., LaNoue, K.F. (2007). 6 Branched Chain Amino Acids (BCAAs) in Brain. In: Lajtha, A., Oja, S.S., Schousboe, A., Saransaari, P. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30373-4_6

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