Branched-chain amino acids and brain metabolism

Sperringer, Justin E.; Addington, Adele; Hutson, Susan M.

doi:10.1007/s11064-017-2261-5

Cited by 218Amino Acid Enzymes and MetabolismMetabolism and Genetic DisordersBiochemical Acid Research Studies

Branched-chain amino acids and brain metabolism

Sperringer, Justin E., Addington, Adele, Hutson, Susan M.·2017·Neurochemical Research

DOI 10.1007/s11064-017-2261-5

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Abstract

This review aims to provide a historical reference of branched-chain amino acid (BCAA) metabolism and provide a link between peripheral and central nervous system (CNS) metabolism of BCAAs.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.

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Glutamate and GABA modulate the hypothalamic-pituitary-adrenal axis.
“In the CNS, BCAAs play roles in protein synthesis, food intake regulation, and serve as nitrogen donors involved in intercellular shuttling and the synthesis of the neurotransmitters glutamate and GABA (both modulate the HPA axis) (336).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [336]
In the central nervous system, branched-chain amino acids play roles in protein synthesis, food intake regulation, and serve as nitrogen donors involved in intercellular shuttling and synthesis of the neurotransmitters glutamate and GABA.
“In the CNS, BCAAs play roles in protein synthesis, food intake regulation, and serve as nitrogen donors involved in intercellular shuttling and the synthesis of the neurotransmitters glutamate and GABA (both modulate the HPA axis) (336).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [336]

mTORC1 Senses Lysosomal Amino Acids Through an Inside-Out Mechanism That Requires the Vacuolar H + -ATPase
Zoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y., & Sabatini, D. M. (2011) · Science · doi:10.1126/science.1207056 · Cited by 1,673 · see citing works
Growing roles for the mTOR pathway
Sarbassov, D. D., Ali, S. M., & Sabatini, D. M. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.09.009 · Cited by 1,556 · see citing works
Hypothalamic mTOR Signaling Regulates Food Intake
Cota, D., Proulx, K., Smith, K. A. B., Kozma, S. C., Thomas, G., Woods, S. C., & Seeley, R. J. (2006) · Science · doi:10.1126/science.1124147 · Cited by 1,278 · see citing works
Biochemistry and physiology of brain ammonia.
Cooper, A. J. L., & Plum, F. (1987) · Physiological Reviews · doi:10.1152/physrev.1987.67.2.440 · Cited by 850 · see citing works
Leucyl-tRNA Synthetase Is an Intracellular Leucine Sensor for the mTORC1-Signaling Pathway
Han, J. M., Jeong, S. J., Park, M. C., Kim, G., Kwon, N. H., Kim, H. K., Ha, S. H., Ryu, S. H., & Kim, S. (2012) · Cell · doi:10.1016/j.cell.2012.02.044 · Cited by 824 · see citing works
Leucine Stimulates Translation Initiation in Skeletal Muscle of Postabsorptive Rats via a Rapamycin-Sensitive Pathway
Anthony, J. C., Yoshizawa, F., Anthony, T. G., Vary, T. C., Jefferson, L. S., & Kimball, S. R. (2000) · Journal of Nutrition · doi:10.1093/jn/130.10.2413 · Cited by 804 · see citing works
The glucose-alanine cycle
Felig, P. (1973) · Metabolism · doi:10.1016/0026-0495(73)90269-2 · Cited by 799 · see citing works
Uptake and Metabolism of Plasma Glutamine by the Small Intestine
Windmueller, H. G., & Spaeth, A. E. (1974) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)42329-6 · Cited by 791 · see citing works
Amino Acid Metabolism in Man
Felig, P. (1975) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.44.070175.004441 · Cited by 789 · see citing works
Regulation of mTORC1 by amino acids
Bar-Peled, L., & Sabatini, D. M. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.03.003 · Cited by 773 · see citing works
Signaling Pathways and Molecular Mechanisms through which Branched-Chain Amino Acids Mediate Translational Control of Protein Synthesis
Kimball, S. R., & Jefferson, L. S. (2006) · Journal of Nutrition · doi:10.1093/jn/136.1.227s · Cited by 637 · see citing works
Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras -driven cancers
Mayers, J. R., Torrence, M. E., Danai, L. V., Papagiannakopoulos, T., Davidson, S. M., Bauer, M. R., Lau, A. N., Ji, B. W., Dixit, P. D., Hosios, A. M., et al. (2016) · Science · doi:10.1126/science.aaf5171 · Cited by 582 · see citing works
Kinetics of Neutral Amino Acid Transport Across the Blood‐Brain Barrier
Smith, Q. R., Momma, S., Aoyagi, M., & Rapoport, S. I. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb01039.x · Cited by 454 · see citing works
Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis
Lotta, L. A., Scott, R. A., Sharp, S. J., Burgess, S., Luan, J., Tillin, T., Schmidt, A. F., Imamura, F., Stewart, I. D., Perry, J. R. B., et al. (2016) · PLOS Medicine · doi:10.1371/journal.pmed.1002179 · Cited by 417 · see citing works
A molecular model of human branched-chain amino acid metabolism
Suryawan, A., Hawes, J. W., Harris, R. A., Shimomura, Y., Jenkins, A. E., & Hutson, S. M. (1998) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/68.1.72 · Cited by 414 · see citing works
Self-citation
Leucine Regulates Translation of Specific mRNAs in L6 Myoblasts through mTOR-mediated Changes in Availability of eIF4E and Phosphorylation of Ribosomal Protein S6*
Kimball, S., Shantz, L., Horetsky, R. L., & Jefferson, L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.17.11647 · Cited by 382 · see citing works
A possible linkage between AMP‐activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway
Kimura, N., Tokunaga, C., Dalal, S., Richardson, C., Yoshino, K., Hara, K., Kemp, B. E., Witters, L. A., Mimura, O., & Yonezawa, K. (2003) · Genes to Cells · doi:10.1046/j.1365-2443.2003.00615.x · Cited by 372 · see citing works
Exogenous Glutamate Concentration Regulates the Metabolic Fate of Glutamate in Astrocytes
McKenna, M. C., Sonnewald, U., Huang, X., Stevenson, J., & Zielke, H. R. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66010386.x · Cited by 361 · see citing works
Mutations in BCKD-kinase Lead to a Potentially Treatable Form of Autism with Epilepsy
Novarino, G., El-Fishawy, P., Kayserili, H., Meguid, N. A., Scott, E. M., Schroth, J., Silhavy, J. L., Kara, M., Khalil, R. O., Ben-Omran, T., et al. (2012) · Science · doi:10.1126/science.1224631 · Cited by 320 · see citing works
Nutrient-Sensing Mechanisms across Evolution
Chantranupong, L., Wolfson, R. L., & Sabatini, D. M. (2015) · Cell · doi:10.1016/j.cell.2015.02.041 · Cited by 320 · see citing works
Transaminase of Branched Chain Amino Acids
Ichihara, A., & Koyama, E. (1966) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a128277 · Cited by 290 · see citing works
The metabolic fates of amino acids and the formation of glutamine in skeletal muscle.
Chang, T. W., & Goldberg, A. L. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34855-x · Cited by 274 · see citing works
Branched-Chain Amino Acid Metabolism: Implications for Establishing Safe Intakes
Hutson, S. M., Sweatt, A. J., & LaNoue, K. F. (2005) · Journal of Nutrition · doi:10.1093/jn/135.6.1557s · Cited by 262 · see citing works
Self-citation
Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export
White, P., Lapworth, A., An, J., Wang, L.-P., McGarrah, R., Stevens, R., Ilkayeva, O., George, T., Muehlbauer, M., Bain, J. R., et al. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.04.006 · Cited by 253 · see citing works
The ketogenic diet and brain metabolism of amino acids: Relationship to the anticonvulsant effect
Yudkoff, M., Daikhin, Y., Melø, T. M., Nissim, I., Sonnewald, U., & Nissim, I. (2007) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.27.061406.093722 · Cited by 202 · see citing works
Branched-chain amino acid oxidation by isolated rat tissue preparations
Shinnick, F. L., & Harper, A. E. (1976) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(76)90016-7 · Cited by 201 · see citing works
Brain Amino Acid Requirements and Toxicity: The Example of Leucine
Yudkoff, M., Daikhin, Y., Nissim, I. B., Horyn, O., Luhovyy, B. L., Lazarow, A., & Nissim, I. (2005) · Journal of Nutrition · doi:10.1093/jn/135.6.1531s · Cited by 196 · see citing works
Nitrogen shuttling between neurons and glial cells during glutamate synthesis
Lieth, E., LaNoue, K. F., Berkich, D. A., Xu, B., Ratz, M., Taylor, C., & Hutson, S. M. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00156.x · Cited by 192 · see citing works
Self-citation
Leucine Metabolism in T Cell Activation: mTOR Signaling and Beyond
Ananieva, E. A., Powell, J. D., & Hutson, S. M. (2016) · Advances in Nutrition · doi:10.3945/an.115.011221 · Cited by 192 · see citing works
Self-citation
Liver Transplantation for Classical Maple Syrup Urine Disease: Long-Term Follow-Up in 37 Patients and Comparative United Network for Organ Sharing Experience
Mazariegos, G. V., Morton, D. H., Sindhi, R. K., Soltys, K. A., Nayyar, N. S., Bond, G., Shellmer, D. A., Shneider, B. L., Vockley, J. E., & Strauss, K. A. (2011) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2011.06.033 · Cited by 184 · see citing works
Role of Branched‐Chain Aminotransferase Isoenzymes and Gabapentin in Neurotransmitter Metabolism
Hutson, S. M., Berkich, D., Drown, P., Xu, B., Aschner, M., & LaNoue, K. F. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.71020863.x · Cited by 171 · cited 3× · see citing works
“In this BCAT cycle, Leu transamination in the astrocyte is catalyzed by BCATm and neuronal transamination is catalyzed by BCATc [49].”
Self-citation
Function of Leucine in Excitatory Neurotransmitter Metabolism in the Central Nervous System
Hutson, S. M., Lieth, E., & LaNoue, K. F. (2001) · Journal of Nutrition · doi:10.1093/jn/131.3.846s · Cited by 157 · see citing works
Self-citation
Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders
Burrage, L. C., Nagamani, S. C. S., Campeau, P. M., & Lee, B. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu123 · Cited by 150 · see citing works
Branched chain aminotransferase isoenzymes. Purification and characterization of the rat brain isoenzyme.
Hall, T. R., Wallin, R., Reinhart, G. A., & Hutson, S. M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53663-2 · Cited by 147 · see citing works
Self-citation
Branched-chain amino acid catabolism: unique segregation of pathway enzymes in organ systems and peripheral nerves
Sweatt, A. J., Wood, M., Suryawan, A., Wallin, R., Willingham, M. C., & Hutson, S. M. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00276.2003 · Cited by 140 · see citing works
Self-citation
Regulation of leucine and alpha-ketoisocaproate metabolism in skeletal muscle.
Hutson, S. M., Cree, T. C., & Harper, A. E. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34371-5 · Cited by 137 · see citing works
Self-citation
Central nervous control of energy and glucose balance: focus on the central melanocortin system
Xu, Y., Elmquist, J. K., & Fukuda, M. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06248.x · Cited by 133 · see citing works
Regulation of leucine and alpha-ketoisocaproic acid metabolism in skeletal muscle. Effects of starvation and insulin.
Hutson, S. M., Zapalowski, C., Cree, T. C., & Harper, A. E. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85908-2 · Cited by 131 · see citing works
Self-citation
Leucine in food mediates some of the postprandial rise in plasma leptin concentrations
Lynch, C. J., Gern, B., Lloyd, C., Hutson, S. M., Eicher, R., & Vary, T. C. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00462.2005 · Cited by 131 · see citing works
Self-citation
Compartmentation of Glutamine, Glutamate, and GABA Metabolism in Neurons and Astrocytes: Functional Implications
Waagepetersen, H. S., Sonnewald, U., & Schousboe, A. (2003) · The Neuroscientist · doi:10.1177/1073858403254006 · Cited by 130 · see citing works
Interactions in the Metabolism of Glutamate and the Branched-Chain Amino Acids and Ketoacids in the CNS
Yudkoff, M. (2016) · Neurochemical Research · doi:10.1007/s11064-016-2057-z · Cited by 130 · see citing works
Branched-Chain Amino Acid Catabolism in Exercise and Liver Disease
Shimomura, Y., Honda, T., Shiraki, M., Murakami, T., Sato, J., Kobayashi, H., Mawatari, K., Obayashi, M., & Harris, R. A. (2006) · Journal of Nutrition · doi:10.1093/jn/136.1.250s · Cited by 128 · see citing works
Regulation of Mammalian Pyruvate and Branched-Chain α-Keto Acid Dehydrogenase Complexes by Phosphorylation — Dephosphorylation
Reed, L. J., Damuni, Z., & Merryfield, M. (1985) · Current topics in cellular regulation · doi:10.1016/b978-0-12-152827-0.50011-6 · Cited by 125 · see citing works
Regulation of brain glutamate metabolism by nitric oxide and S-nitrosylation
Raju, K., Doulias, P., Evans, P., Krizman, E. N., Jackson, J. G., Horyn, O., Daikhin, Y., Nissim, I. B., Yudkoff, M., Nissim, I., et al. (2015) · Science Signaling · doi:10.1126/scisignal.aaa4312 · Cited by 124 · see citing works
Astrocyte Leucine Metabolism: Significance of Branched‐Chain Amino Acid Transamination
Yudkoff, M., Daikhin, Y., Grunstein, L., Nissim, I. B., Stern, J., Pleasure, D., & Nissim, I. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66010378.x · Cited by 121 · see citing works
TOR on the brain
Garelick, M. G., & Kennedy, B. K. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.08.030 · Cited by 120 · see citing works
Impaired growth and neurological abnormalities in branched-chain α-keto acid dehydrogenase kinase-deficient mice
Joshi, M., Jeoung, N. H., Obayashi, M., Hattab, E. M., Brocken, E., Liechty, E. A., Kubek, M. J., Vattem, K. M., Wek, R. C., & Harris, R. A. (2006) · Biochemical Journal · doi:10.1042/bj20060869 · Cited by 118 · see citing works
Identification of mitochondrial branched chain aminotransferase and its isoforms in rat tissues.
Hutson, S. M., Wallin, R., & Hall, T. R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49589-6 · Cited by 117 · see citing works
Self-citation
Biochemical correlates of neuropsychiatric illness in maple syrup urine disease
Muelly, E. R., Moore, G. J., Bunce, S. C., Mack, J. A., Bigler, D. C., Morton, D. H., & Strauss, K. A. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67217 · Cited by 117 · see citing works
Brain microvessels take up large neutral amino acids in exchange for glutamine. Cooperative role of Na+-dependent and Na+-independent systems.
Cangiano, C., Cardelli‐Cangiano, P., James, J. H., Fanelli, F. R., Patrizi, M., Brackett, K. A., Ström, R., & Fischer, J. E. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32149-5 · Cited by 110 · see citing works
Role of Pyruvate Carboxylase in Facilitation of Synthesis of Glutamate and Glutamine in Cultured Astrocytes
Gamberino, W. C., Berkich, D. A., Lynch, C. J., Xu, B., & LaNoue, K. F. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69062312.x · Cited by 107 · see citing works
A Novel Branched-chain Amino Acid Metabolon
Islam, M. M., Wallin, R., Wynn, R. M., Conway, M., Fujii, H., Mobley, J. A., Chuang, D. T., & Hutson, S. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700198200 · Cited by 107 · see citing works
Self-citation
Effects of Ingested Steak and Infused Leucine on Forelimb Metabolism in Man and the Fate of the Carbon Skeletons and Amino Groups of Branched-Chain Amino Acids
Elia, M., & Livesey, G. (1983) · Clinical Science · doi:10.1042/cs0640517 · Cited by 98 · see citing works
Branched-chain Amino Acid Metabolon
Islam, M. M., Nautiyal, M., Wynn, R., Mobley, J. A., Chuang, D., & Hutson, S. M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.048777 · Cited by 98 · see citing works
Self-citation
Activity state of the branched chain α-ketoacid dehydrogenase complex in heart, liver, and kidney of normal, fasted, diabetic, and protein-starved rats
Gillim, S. E., Paxton, R., Cook, G. A., & Harris, R. A. (1983) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(83)80119-3 · Cited by 98 · see citing works
Cytosolic Branched Chain Aminotransferase (BCATc) Regulates mTORC1 Signaling and Glycolytic Metabolism in CD4+ T Cells
Ananieva, E. A., Patel, C. H., Drake, C. H., Powell, J. D., & Hutson, S. M. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.554113 · Cited by 98 · see citing works
Self-citation
Deconvoluting mTOR biology
Weber, J. D., & Gutmann, D. H. (2012) · Cell Cycle · doi:10.4161/cc.11.2.19022 · Cited by 97 · see citing works
Interrelationships of Leucine and Glutamate Metabolism in Cultured Astrocytes
Yudkoff, M., Daikhin, Y., Lin, Z., Nissim, L., Stern, J., Pleasure, D., & Nissim, I. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.62031192.x · Cited by 97 · see citing works
Glutamine Synthetase: Role in Neurological Disorders
Jayakumar, A., & Norenberg, M. D. (2016) · Advances in neurobiology · doi:10.1007/978-3-319-45096-4_13 · Cited by 97 · see citing works
Role of mitochondrial transamination in branched chain amino acid metabolism.
Hutson, S. M., Fenstermacher, D., & Mahar, C. Q. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68969-0 · Cited by 93 · see citing works
Self-citation
Rate of Glutamate Synthesis from Leucine in Rat Brain Measured In Vivo by 15N NMR
Kanamori, K., Ross, B. D., & Kondrat, R. W. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70031304.x · Cited by 89 · see citing works
Branched‐chain amino acids and neurotransmitter metabolism: Expression of cytosolic branched‐chain aminotransferase (BCATc) in the cerebellum and hippocampus
Sweatt, A. J., Garcia-Espinosa, M. A., Wallin, R., & Hutson, S. M. (2004) · The Journal of Comparative Neurology · doi:10.1002/cne.20200 · Cited by 89 · see citing works
Self-citation
Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function
Garza-Lombó, C., & Gonsebatt, M. E. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00157 · Cited by 89 · see citing works
New Insights into the Compartmentation of Glutamate and Glutamine in Cultured Rat Brain Astrocytes
McKenna, M. C., Tildón, J. T., Stevenson, J., & Huang, X. (2007) · Developmental Neuroscience · doi:10.1159/000111431 · Cited by 87 · see citing works
Two Novel Mutations in theBCKDK(Branched-Chain Keto-Acid Dehydrogenase Kinase) Gene Are Responsible for a Neurobehavioral Deficit in Two Pediatric Unrelated Patients
García‐Cazorla, À., Oyarzábal, A., Fort, J., Robles, C. L., Castejón, E., Ruiz‐Sala, P., Bodoy, S., Merinero, B., Sala, A. L., Dopazo, J., et al. (2014) · Human Mutation · doi:10.1002/humu.22513 · Cited by 86 · see citing works
Subcellular Distribution of Branched-Chain Aminotransferase Activity in Rat Tissues
Hutson, S. M. (1988) · Journal of Nutrition · doi:10.1093/jn/118.12.1475 · Cited by 83 · see citing works
Self-citation
Distribution of Key Enzymes of Branched-chain Amino Acid Metabolism in Glial and Neuronal Cells in Culture
Bixel, M. G., Shimomura, Y., Hutson, S. M., & Hamprecht, B. (2001) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540104900314 · Cited by 79 · see citing works
Self-citation
Widespread neuronal expression of branched‐chain aminotransferase in the CNS: implications for leucine/glutamate metabolism and for signaling by amino acids
Garcia-Espinosa, M. A., Wallin, R., Hutson, S. M., & Sweatt, A. J. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04332.x · Cited by 78 · see citing works
Self-citation
Cellular Distribution of Branched-chain Amino Acid Aminotransferase Isoenzymes Among Rat Brain Glial Cells in Culture
Bixel, M. G., Hutson, S. M., & Hamprecht, B. (1997) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215549704500506 · Cited by 78 · see citing works
Self-citation
Hypothalamic roles of mTOR complex I: integration of nutrient and hormone signals to regulate energy homeostasis
Hu, F., Xu, Y., & Liu, F. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00121.2016 · Cited by 77 · see citing works
Regulation of the branched-chain α-ketoacid dehydrogenase and elucidation of a molecular basis for maple syrup urine disease
Harris, R. A., Zhang, B., Goodwin, G. W., et al. (1990) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(90)90021-s · Cited by 76 · see citing works
Glutamate and γ‐Aminobutyric Acid Neurotransmitter Systems in the Acute Phase of Maple Syrup Urine Disease and Citrullinemia Encephalopathies in Newborn Calves
Dodd, P. R., Williams, S. H., Gundlach, A. L., et al. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09409.x · Cited by 75 · see citing works
Maple syrup urine disease: Clinical, eeg, and plasma amino acid correlations with a theoretical mechanism of acute neurotoxicity
Korein, J., Sansaricq, C., Kalmijn, M., et al. (1994) · International Journal of Neuroscience · doi:10.3109/00207459408986065 · Cited by 72 · see citing works
Distribution of the branched chain aminotransferase proteins in the human brain and their role in glutamate regulation
Hull, J., Hindy, M. E., Kehoe, P. G., Chalmers, K. A., Love, S., & Conway, M. E. (2012) · Journal of Neurochemistry · doi:10.1111/jnc.12044 · Cited by 72 · see citing works
The Physiologic and Nutritional Significance of Plasma‐free Amino Acid Levels
Abumrad, N. N., & Miller, B. M. (1983) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607183007002163 · Cited by 69 · see citing works
Crystal Structures of Branched-Chain Amino Acid Aminotransferase Complexed with Glutamate and Glutarate: True Reaction Intermediate and Double Substrate Recognition of the Enzyme,
Goto, M., MIYAHARA, I., Hayashi, H., et al. (2003) · Biochemistry · doi:10.1021/bi026722f · Cited by 69 · see citing works
Neurological Damage in MSUD: The Role of Oxidative Stress
Sitta, Â., Ribas, G. S., Mescka, C. P., Barschak, A. G., Wajner, M., & Vargas, C. R. (2013) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-013-0002-0 · Cited by 66 · see citing works
[ 15 N] leucine as a source of [ 15 N] glutamate in organotypic cerebellar explants
Yudkoff, M., Nissim, I., Kim, S., et al. (1983) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(83)90985-3 · Cited by 60 · see citing works
Regulation of Branched-Chain Amino Acid Metabolism in the Lactating Rat
DeSantiago, S., Torres, N., Suryawan, A., et al. (1998) · Journal of Nutrition · doi:10.1093/jn/128.7.1165 · Cited by 60 · see citing works
Is there In Vivo Evidence for Amino Acid Shuttles Carrying Ammonia from Neurons to Astrocytes?
Rothman, D. L., Feyter, H. M. D., Maciejewski, P. K., & Behar, K. L. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0898-7 · Cited by 56 · see citing works
Leucine‐nitrogen metabolism in the brain of conscious rats: its role as a nitrogen carrier in glutamate synthesis in glial and neuronal metabolic compartments
Sakai, R., Cohen, D. M., Henry, J. F., Burrin, D. G., & Reeds, P. J. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02179.x · Cited by 54 · see citing works
Uptake and metabolism of amino acids by the dog liver perfused in situ
McMenamy, R. H., Shoemaker, W. C., Richmond, J. E., et al. (1962) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1962.202.3.407 · Cited by 54 · see citing works
BCAA Metabolism and NH3 Homeostasis
Conway, M. E., & Hutson, S. M. (2016) · Advances in Neurobiology · doi:10.1007/978-3-319-45096-4_5 · Cited by 53 · see citing works
Self-citation
Cloning and Expression of the Mammalian Cytosolic Branched Chain Aminotransferase Isoenzyme
Hutson, S. M., Bledsoe, R. K., Hall, T. R., & Dawson, P. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.51.30344 · Cited by 50 · see citing works
Self-citation
Hypervalinemia and hyperleucine‐isoleucinemia caused by mutations in the branched‐chain‐amino‐acid aminotransferase gene
Wang, X. L., Li, C. J., Xing, Y., Yang, Y., & Jia, J. (2015) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-015-9814-z · Cited by 49 · see citing works
Coupling nutrient sensing to metabolic homoeostasis: the role of the mammalian target of rapamycin complex 1 pathway
André, C., & Cota, D. (2012) · Proceedings of The Nutrition Society · doi:10.1017/s0029665112000754 · Cited by 45 · see citing works
[23] Determination of activity and activity state of branched-chain α-keto acid dehydrogenase in rat tissues
Goodwin, G. W., Zhang, B., Paxton, R., et al. (1988) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(88)66025-3 · Cited by 42 · see citing works
Branched chain alpha-keto acid oxidative decarboxylation in skeletal muscle mitochondria. Effect of isolation procedure and mitochondrial delta pH.
Hutson, S. M. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38516-2 · Cited by 41 · see citing works
Self-citation
Crystal Structures of Human Mitochondrial Branched Chain Aminotransferase Reaction Intermediates: Ketimine and Pyridoxamine Phosphate Forms
Yennawar, N. H., Conway, M. E., Yennawar, H. P., Farber, G. K., & Hutson, S. M. (2002) · Biochemistry · doi:10.1021/bi020221c · Cited by 40 · see citing works
Self-citation
Human mitochondrial branched chain aminotransferase: structural basis for substrate specificity and role of redox active cysteines
Conway, M. E., Yennawar, N. H., Wallin, R., Poole, L. B., & Hutson, S. M. (2003) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/s1570-9639(03)00051-7 · Cited by 37 · see citing works
Self-citation
Oral Leucine Supplementation Is Sensed by the Brain but neither Reduces Food Intake nor Induces an Anorectic Pattern of Gene Expression in the Hypothalamus
Zampieri, T. T., Pedroso, J. A. B., Furigo, I. C., Tirapegui, J., & Donato, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084094 · Cited by 35 · see citing works
Interaction between glutamate dehydrogenase (GDH) and l-leucine catabolic enzymes: Intersecting metabolic pathways
Hutson, S. M., Islam, M. M., & Zaganas, I. V. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2011.05.001 · Cited by 34 · see citing works
Self-citation
Human mitochondrial and cytosolic branched-chain aminotransferases are cysteine S-conjugate β-lyases, but turnover leads to inactivation
Cooper, A. J. L., Bruschi, S. A., Conway, M. E., & Hutson, S. M. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)01513-7 · Cited by 29 · see citing works
Self-citation
Serum Markers of Neurodegeneration in Maple Syrup Urine Disease
Scaini, G., Tonon, T., de Souza, C. F. M., Schuk, P. F., Ferreira, G. C., Neto, J. S., Amorin, T., Schwartz, I. V. D., & STRECK, E. L. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0116-8 · Cited by 27 · see citing works
The case for regulating indispensable amino acid metabolism: the branched-chain α-keto acid dehydrogenase kinase-knockout mouse
Hutson, S. M. (2006) · Biochemical Journal · doi:10.1042/bj20061506 · Cited by 25 · see citing works
Self-citation
Crystal Structures of Complexes of the Branched-Chain Aminotransferase from Deinococcus radiodurans with α-Ketoisocaproate and l- Glutamate Suggest the Radiation Resistance of This Enzyme for Catalysis
Chen, C.-D., Lin, C., Chuankhayan, P., et al. (2012) · Journal of Bacteriology · doi:10.1128/jb.01659-12 · Cited by 25 · see citing works
Chairman's Remarks: Thoughts on the Role of Branched‐Chain α‐Keto Acid Dehydrogenase Complex in Nitrogen Metabolism
Harper, A. E. (1989) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1989.tb15003.x · Cited by 24 · see citing works
Altered Expression of Human Mitochondrial Branched Chain Aminotransferase in Dementia with Lewy Bodies and Vascular Dementia
Ashby, E. L., Kierzkowska, M., Hull, J., Kehoe, P. G., Hutson, S. M., & Conway, M. E. (2016) · Neurochemical Research · doi:10.1007/s11064-016-1855-7 · Cited by 23 · see citing works
Self-citation
Novel Physiological Functions of Branched-Chain Amino Acids
Shimomura, Y., Kitaura, Y., Kadota, Y., Ishikawa, T., KONDO, Y., Xu, M., Ota, M., Morishita, Y., Bariuan, J. V., & Zhen, H. (2015) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.61.s112 · Cited by 23 · see citing works
Structural analysis of mycobacterial branched-chain aminotransferase: implications for inhibitor design
Castell, A., Mille, C., & Unge, T. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910004877 · Cited by 18 · see citing works
Morphological Alterations and Cell Death Provoked by the Branched-Chain α-Amino Acids Accumulating in Maple Syrup Urine Disease in Astrocytes from Rat Cerebral Cortex
Funchal, C., Gottfried, C., de Almeida, L. M. V., dos Santos, A. Q., Wajner, M., & Pessoa-Pureur, R. (2005) · Cellular and molecular neurobiology · doi:10.1007/s10571-005-4938-6 · Cited by 17 · see citing works
In vivo N-15 MRS study of glutamate metabolism in the rat brain
Kanamori, K. (2016) · Analytical Biochemistry · doi:10.1016/j.ab.2016.08.025 · Cited by 17 · see citing works
Branched‐chain amino acids accumulating in maple syrup urine disease induce morphological alterations in C6 glioma cells probably through reactive species
Pelaez, P. D. L., Funchal, C., Loureiro, S. O., et al. (2007) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2007.01.001 · Cited by 15 · see citing works
Erratum to: Serum Markers of Neurodegeneration in Maple Syrup Urine Disease
Scaini, G., Tonon, T., de Souza, C. F. M., et al. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0263-y · Cited by 1 · see citing works
Glucose transporter proteins in brain: Delivery of glucose to neurons and glia
Vannucci, S. J., Maher, F., & Simpson, I. A. (1997) · Glia · doi:10.1002/(sici)1098-1136(199709)21:1

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The Microbiota-Gut-Brain Axis
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier
Hladky, S. B., & Barrand, M. A. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0113-6 · Cited by 206 · see citing works
Branched-chain amino acids govern the high learning ability phenotype in tokai high avoider (THA) rats
Shida, Y., Endo, H., Owada, S., Inagaki, Y., Sumiyoshi, H., Kamiya, A., Eto, T., & Tatemichi, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-02591-7 · Cited by 6 · see citing works

Electroencephalograms in a Case of Maple Syrup Urine Disease: Their Relation to Serum Levels of Branched-Chain Amino Acids
Iinuma, K., Saito, T., Wada, Y., et al. (1976) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.120.191 · Cited by 4 · see citing works
Interrelation between the Metabolism of L-Isoleucine and L-Allo-Isoleucine in Patients with Maple Syrup Urine Disease
Wendel, U., Langenbeck, U., & Seakins, J. W. T. (1989) · Pediatric Research · doi:10.1203/00006450-198901000-00003 · Cited by 24 · see citing works
Serial MR Images and MRS Following Treatment in a Newborn with Maple Syrup Urine Disease
Lin, Y., Liu, M.-Y., Jaw, T., et al. (2012) · Journal of Radiological Science · doi:10.6698/jrs.201209_3703.07
[Isolated isoleucine deficiency in diet therapy of a case of maple syrup urine disease].
Sanjurjo, P., Centeno, C., Vallo, A., et al. (1983) · PubMed · Cited by 2 · see citing works
MAPLE SYRUP URINE DISEASE, WITH PARTICULAR REFERENCE TO DIETOTHERAPY
Snyderman, S. E., Norton, P. M., Roitman, E., & Holt, L. E. (1964) · PEDIATRICS · doi:10.1542/peds.34.4.454 · Cited by 226 · see citing works

Authors: Sperringer, J. E., Addington, A., & Hutson, S. M.
Affiliations: Virginia Tech (US)
Corresponding author: Sperringer, Justin E.
ORCID: Addington, Adele
Venue: Neurochemical Research
Publisher: Springer Science and Business Media LLC
Published: 2017-04-18
Volume: 42
Issue: 6
Pages: 1697-1709
ISSN: 0364-3190 (ISSN-L)
1573-6903
DOI: 10.1007/s11064-017-2261-5
OpenAlex: W2606152360
Cited by: 218
References: 105
Citations by year: 2026: 19 · 2025: 29 · 2024: 27 · 2023: 31 · 2022: 24 · 2021: 30 · 2020: 24 · 2019: 19 · 2018: 13 · 2017: 1 · 2016: 1
FWCI: 7.89
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (unspecified)
Locations: Neurochemical Research (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
Keywords: branched-chain amino acids, brain metabolism, leucine, isoleucine, valine, branched-chain ketoacid dehydrogenase, branched-chain amino acid aminotransferase, maple syrup urine disease, mTOR signaling, central nervous system, neurotransmitter synthesis, food intake regulation, neurological disorders
MeSH terms: Amino Acids, Branched-Chain, Transaminases, Animals, Brain, Humans, Leucine, Maple Syrup Urine Disease, Valine, Signal Transduction

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Branched-chain amino acids and brain metabolism

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