{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:45:09Z","timestamp":1787319909668,"version":"build-2736575974"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T00:00:00Z","timestamp":1658102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013099","name":"Scientific Research Fund of Liaoning Provincial Education Department","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013099","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007300","name":"China Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>Branched-chain amino acids (BCAAs), composed of leucine, isoleucine, and valine, are important essential amino acids in human physiology. Decades of studies have revealed their roles in protein synthesis, regulating neurotransmitter synthesis, and the mechanistic target of rapamycin (mTOR). BCAAs are found to be related to many metabolic disorders, such as insulin resistance, obesity, and heart failure. Also, many diseases are related to the alteration of the BCAA catabolism enzyme branched-chain \u03b1-keto acid dehydrogenase kinase (BCKDK), including maple syrup urine disease, human autism with epilepsy, and so on. In this review, diseases and the corresponding therapies are discussed after the introduction of the catabolism and detection methods of BCAAs and BCKDK. Also, the interaction between microbiota and BCAAs is highlighted.<\/jats:p>","DOI":"10.3389\/fnut.2022.932670","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T01:42:55Z","timestamp":1658108575000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":79,"title":["The Role of Branched-Chain Amino Acids and Branched-Chain \u03b1-Keto Acid Dehydrogenase Kinase in Metabolic Disorders"],"prefix":"10.3389","volume":"9","author":[{"given":"Chuang","family":"Du","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan-Shan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1146\/annurev-physiol-020518-114455","article-title":"Branched chain amino acids.","volume":"81","author":"Neinast","year":"2019","journal-title":"Annu Rev Physiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/nrendo.2014.171","article-title":"Branched-chain amino acids in metabolic signalling and insulin resistance.","volume":"10","author":"Lynch","year":"2014","journal-title":"Nat Rev Endocrinol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1126\/science.aav0558","article-title":"Branched-chain amino acids in disease.","volume":"363","author":"White","year":"2019","journal-title":"Science."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-018-0271-1","article-title":"Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements.","volume":"15","author":"Hole\u00e8ek","year":"2018","journal-title":"Nutr Metab."},{"key":"B5","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/j.cmet.2014.09.003","article-title":"Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism.","volume":"20","author":"Shin","year":"2014","journal-title":"Cell Metab."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/genes13020233","article-title":"A gain-of-function mutation on BCKDK gene and its possible pathogenic role in branched-chain amino acid metabolism.","volume":"13","author":"Maguolo","year":"2022","journal-title":"Genes."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/10408398.2021.1977910","article-title":"Branched chain amino acids-friend or foe in the control of energy substrate turnover and insulin sensitivity?","author":"Supruniuk","year":"2021","journal-title":"Crit Rev Food Sci Nutr"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2019.121819","article-title":"Analytical strategies for the determination of amino acids: past, present and future trends.","volume":"1132","author":"Ferr\u00e9","year":"2019","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2385","DOI":"10.1002\/jssc.201000171","article-title":"Capillary electrophoresis-mass spectrometry for the analysis of amino acids.","volume":"33","author":"Desiderio","year":"2010","journal-title":"J Sep Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1007\/s00726-016-2212-5","article-title":"A novel liquid chromatography tandem mass spectrometry method for simultaneous determination of branched-chain amino acids and branched-chain \u03b1-keto acids in human plasma.","volume":"48","author":"Li","year":"2016","journal-title":"Amino Acids."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1007\/s00216-018-1522-8","article-title":"Development and validation of a simple LC-MS\/MS method for the simultaneous quantitative determination of trimethylamine-N-oxide and branched chain amino acids in human serum.","volume":"411","author":"Le","year":"2019","journal-title":"Anal Bioanal Chem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"E629","DOI":"10.1152\/ajpendo.00384.2020","article-title":"Metabolic flux analysis of branched-chain amino and keto acids (BCAA, BCKA) and \u03b2-hydroxy \u03b2-methylbutyric acid across multiple organs in the pig.","volume":"320","author":"Ten Have","year":"2021","journal-title":"Am J Physiol Endocrinol Metab."},{"key":"B13","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.jchromb.2015.12.019","article-title":"Simultaneous quantification of cardiovascular disease related metabolic risk factors using liquid chromatography tandem mass spectrometry in human serum.","volume":"100","author":"Wang","year":"2016","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081144","article-title":"Rapid and precise measurement of serum branched-chain and aromatic amino acids by isotope dilution liquid chromatography tandem mass spectrometry.","volume":"8","author":"Yang","year":"2013","journal-title":"PLoS One."},{"key":"B15","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.jchromb.2012.07.029","article-title":"Comparison of amino acid derivatization reagents for LC-ESI-MS analysis. Introducing a novel phosphazene-based derivatization reagent.","volume":"904","author":"Rebane","year":"2012","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158261","article-title":"Determination of branched-chain amino acids in food supplements and human plasma by a CE-MS\/MS method with enhanced resolution.","volume":"22","author":"Piestansky","year":"2021","journal-title":"Int J Mol Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1002\/elps.200305791","article-title":"Qualitative and quantitative analysis of amino acids by capillary electrophoresis-electrospray ionization-tandem mass spectrometry.","volume":"25","author":"Soga","year":"2004","journal-title":"Electrophoresis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/978-1-61779-445-2_8","article-title":"Amino acid analysis by capillary electrophoresis-mass spectrometry.","volume":"828","author":"Hirayama","year":"2012","journal-title":"Methods Mol Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1007\/s13361-015-1119-9","article-title":"Pyrylium salts as reactive matrices for MALDI-MS imaging of biologically active primary amines.","volume":"26","author":"Shariatgorji","year":"2015","journal-title":"J Am Soc Mass Spectrom."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-015-0926-0","article-title":"Mass spectrometry imaging of amino neurotransmitters: a comparison of derivatization methods and application in mouse brain tissue.","volume":"12","author":"Esteve","year":"2016","journal-title":"Metabolomics."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3298","DOI":"10.1038\/s41596-021-00538-w","article-title":"Spatial visualization of comprehensive brain neurotransmitter systems and neuroactive substances by selective in situ chemical derivatization mass spectrometry imaging.","volume":"16","author":"Shariatgorji","year":"2021","journal-title":"Nat Protoc."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1016\/j.cmet.2018.04.015","article-title":"The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase.","volume":"27","author":"White","year":"2018","journal-title":"Cell Metab."},{"key":"B23","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1002\/ame2.12038","article-title":"The pattern of plasma BCAA concentration and liver Bckdha gene expression in GK rats during T2D progression.","volume":"1","author":"Zhang","year":"2018","journal-title":"Animal Model Exp Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4459","DOI":"10.21037\/tlcr-21-885","article-title":"BCKDK alters the metabolism of non-small cell lung cancer.","volume":"10","author":"Wang","year":"2021","journal-title":"Transl Lung Cancer Res."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/biom11101414","article-title":"Gut microbiota as the link between elevated BCAA serum levels and insulin resistance.","volume":"11","author":"Gojda","year":"2021","journal-title":"Biomolecules."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2020.126648","article-title":"Dietary Luffa cylindrica (L.) roem promotes branched-chain amino acid catabolism in the circulation system via gut microbiota in diet-induced obese mice.","volume":"320","author":"Zhang","year":"2020","journal-title":"Food Chem."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.789325","article-title":"Uncovering the role of gut microbiota in amino acid metabolic disturbances in heart failure through metagenomic analysis.","volume":"8","author":"Hayashi","year":"2021","journal-title":"Front Cardiovasc Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nature18646","article-title":"Human gut microbes impact host serum metabolome and insulin sensitivity.","volume":"535","author":"Pedersen","year":"2016","journal-title":"Nature."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23074022","article-title":"The critical role of the branched chain amino acids (BCAAs) catabolism-regulating enzymes, branched-chain aminotransferase (BCAT) and branched-chain alpha-keto acid dehydrogenase (BCKD), in human pathophysiology.","volume":"23","author":"Dimou","year":"2022","journal-title":"Int J Mol Sci."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75542-3","article-title":"Supplementation of branched-chain amino acids decreases fat accumulation in the liver through intestinal microbiota-mediated production of acetic acid.","volume":"10","author":"Iwao","year":"2020","journal-title":"Sci Rep."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103342","article-title":"Bacteroides spp. promotes branched-chain amino acid catabolism in brown fat and inhibits obesity.","volume":"24","author":"Yoshida","year":"2021","journal-title":"iScience."},{"key":"B32","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.diabet.2018.09.004","article-title":"A dietary intervention with functional foods reduces metabolic endotoxaemia and attenuates biochemical abnormalities by modifying faecal microbiota in people with type 2 diabetes.","volume":"45","author":"Medina-Vera","year":"2019","journal-title":"Diabetes Metab."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax6208","article-title":"Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism.","volume":"6","author":"Zeng","year":"2020","journal-title":"Sci Adv."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3207","DOI":"10.1038\/s41396-021-00998-8","article-title":"Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients.","volume":"15","author":"Ni","year":"2021","journal-title":"Isme J."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.756491","article-title":"Ginsenoside Rb1 ameliorates glycemic disorder in mice with high fat diet-induced obesity via regulating gut microbiota and amino acid metabolism.","volume":"12","author":"Yang","year":"2021","journal-title":"Front Pharmacol."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2018.e00830","article-title":"Intermittent administration of a leucine-deprived diet is able to intervene in type 2 diabetes in db\/db mice.","volume":"4","author":"Wei","year":"2018","journal-title":"Heliyon."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.1007\/s00726-016-2308-y","article-title":"Metabolic shifts and structural changes in the gut microbiota upon branched-chain amino acid supplementation in middle-aged mice.","volume":"48","author":"Yang","year":"2016","journal-title":"Amino Acids."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/nu13082887","article-title":"Sargassum fusiforme alginate relieves hyperglycemia and modulates intestinal microbiota and metabolites in type 2 diabetic mice.","volume":"13","author":"Liu","year":"2021","journal-title":"Nutrients."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2021.109080","article-title":"The probiotic effects of AB23A on high-fat-diet-induced non-alcoholic fatty liver disease in mice may be associated with suppressing the serum levels of lipopolysaccharides and branched-chain amino acids.","volume":"714","author":"Xia","year":"2021","journal-title":"Arch Biochem Biophys."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84355-x","article-title":"The role of gut microbiota and amino metabolism in the effects of improvement of islet \u03b2-cell function after modified jejunoileal bypass.","volume":"11","author":"Tan","year":"2021","journal-title":"Sci Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1002\/jcsm.12781","article-title":"Gut barrier and microbiota changes with glycine and branched-chain amino acid supplementation in chronic haemodialysis patients.","volume":"12","author":"Genton","year":"2021","journal-title":"J Cachexia Sarcopenia Muscle."},{"key":"B42","doi-asserted-by":"publisher","first-page":"E1552","DOI":"10.1152\/ajpendo.00134.2007","article-title":"Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism.","volume":"293","author":"She","year":"2007","journal-title":"Am J Physiol Endocrinol Metab."},{"key":"B43","doi-asserted-by":"publisher","first-page":"E1175","DOI":"10.1152\/ajpendo.00630.2012","article-title":"Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity.","volume":"304","author":"Lackey","year":"2013","journal-title":"Am J Physiol Endocrinol Metab."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101261","article-title":"Insulin action, type 2 diabetes, and branched-chain amino acids: a two-way street.","volume":"52","author":"White","year":"2021","journal-title":"Mol Metab."},{"key":"B45","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1210\/me.2014-1275","article-title":"Inflammation and ER stress regulate branched-chain amino acid uptake and metabolism in adipocytes.","volume":"29","author":"Burrill","year":"2015","journal-title":"Mol Endocrinol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.2337\/dc12-1805","article-title":"Type 2 diabetes: etiology and reversibility.","volume":"36","author":"Taylor","year":"2013","journal-title":"Diabetes Care."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.2337\/db18-0927","article-title":"Targeting BCAA catabolism to treat obesity-associated insulin resistance.","volume":"68","author":"Zhou","year":"2019","journal-title":"Diabetes."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/srep20594","article-title":"Branched-chain and aromatic amino acid profiles and diabetes risk in Chinese populations.","volume":"6","author":"Chen","year":"2016","journal-title":"Sci Rep."},{"key":"B49","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1007\/s00125-009-1637-8","article-title":"Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men.","volume":"53","author":"Tai","year":"2010","journal-title":"Diabetologia."},{"key":"B50","doi-asserted-by":"publisher","first-page":"15597","DOI":"10.1074\/jbc.RA120.013121","article-title":"Branched-chain ketoacid overload inhibits insulin action in the muscle.","volume":"295","author":"Biswas","year":"2020","journal-title":"J Biol Chem."},{"key":"B51","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1172\/jci107593","article-title":"Splanchnic glucose and amino acid metabolism in obesity.","volume":"53","author":"Felig","year":"1974","journal-title":"J Clin Invest."},{"key":"B52","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1093\/ajcn.82.2.355","article-title":"Whole-body protein anabolic response is resistant to the action of insulin in obese women.","volume":"82","author":"Chevalier","year":"2005","journal-title":"Am J Clin Nutr."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e439","DOI":"10.1016\/j.orcp.2013.07.003","article-title":"Regulation of hepatic branched-chain \u03b1-ketoacid dehydrogenase complex in rats fed a high-fat diet.","volume":"7","author":"Kadota","year":"2013","journal-title":"Obes Res Clin Pract."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-021-00107-6","article-title":"BCKDK: an emerging kinase target for metabolic diseases and cancer.","volume":"20","author":"East","year":"2021","journal-title":"Nat Rev Drug Discov."},{"key":"B55","doi-asserted-by":"publisher","first-page":"E73","DOI":"10.1152\/ajpendo.00256.2018","article-title":"Berberine alleviates insulin resistance by reducing peripheral branched-chain amino acids.","volume":"316","author":"Yue","year":"2019","journal-title":"Am J Physiol Endocrinol Metab."},{"key":"B56","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.cmet.2006.05.003","article-title":"Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1. S6K1.","volume":"3","author":"Um","year":"2006","journal-title":"Cell Metab."},{"key":"B57","doi-asserted-by":"publisher","first-page":"14056","DOI":"10.1073\/pnas.0706517104","article-title":"Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance.","volume":"104","author":"Tremblay","year":"2007","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.2337\/db06-1016","article-title":"The mammalian target of rapamycin pathway regulates nutrient-sensitive glucose uptake in man.","volume":"56","author":"Krebs","year":"2007","journal-title":"Diabetes."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00395","article-title":"Judicious Toggling of mTOR Activity to combat insulin resistance and cancer: current evidence and perspectives.","volume":"7","author":"Ong","year":"2016","journal-title":"Front Pharmacol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1007\/s11154-021-09652-2","article-title":"AKT ISOFORMS-AS160-GLUT4: the defining axis of insulin resistance.","volume":"22","author":"Sharma","year":"2021","journal-title":"Rev Endocr Metab Disord."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.2337\/db16-1475","article-title":"Alterations in 3-Hydroxyisobutyrate and FGF21 metabolism are associated with protein ingestion-induced insulin resistance.","volume":"66","author":"Harris","year":"2017","journal-title":"Diabetes."},{"key":"B62","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.cmet.2009.02.002","article-title":"A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance.","volume":"9","author":"Newgard","year":"2009","journal-title":"Cell Metab."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1161\/circulationaha.115.020226","article-title":"Catabolic defect of branched-chain amino acids promotes heart failure.","volume":"133","author":"Sun","year":"2016","journal-title":"Circulation."},{"key":"B64","doi-asserted-by":"publisher","first-page":"E1046","DOI":"10.1152\/ajpendo.00097.2018","article-title":"Cardiac branched-chain amino acid oxidation is reduced during insulin resistance in the heart.","volume":"315","author":"Fillmore","year":"2018","journal-title":"Am J Physiol Endocrinol Metab."},{"key":"B65","doi-asserted-by":"publisher","first-page":"H1160","DOI":"10.1152\/ajpheart.00114.2016","article-title":"Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction.","volume":"311","author":"Wang","year":"2016","journal-title":"Am J Physiol Heart Circ Physiol."},{"key":"B66","doi-asserted-by":"crossref","DOI":"10.1186\/s12933-019-0892-3","article-title":"Impaired branched chain amino acid oxidation contributes to cardiac insulin resistance in heart failure.","volume":"18","author":"Uddin","year":"2019","journal-title":"Cardiovasc Diabetol."},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3390\/nu9101047","article-title":"Is Branched-chain amino acids supplementation an efficient nutritional strategy to alleviate skeletal muscle damage? a systematic review.","volume":"9","author":"Four\u00e9","year":"2017","journal-title":"Nutrients."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0160447","article-title":"A spontaneous missense mutation in branched chain keto acid dehydrogenase kinase in the rat affects both the central and peripheral nervous systems.","volume":"11","author":"Zigler","year":"2016","journal-title":"PLoS One."},{"key":"B69","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1042\/bj20060869","article-title":"Impaired growth and neurological abnormalities in branched-chain alpha-keto acid dehydrogenase kinase-deficient mice.","volume":"400","author":"Joshi","year":"2006","journal-title":"Biochem J."},{"key":"B70","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1126\/science.1224631","article-title":"Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy.","volume":"338","author":"Novarino","year":"2012","journal-title":"Science."},{"key":"B71","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1002\/humu.22513","article-title":"Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase kinase) gene are responsible for a neurobehavioral deficit in two pediatric unrelated patients.","volume":"35","author":"Garc\u00eda-Cazorla","year":"2014","journal-title":"Hum Mutat."},{"key":"B72","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s10863-012-9479-3","article-title":"A study of molecular changes relating to energy metabolism and cellular stress in people with Huntington\u2019s disease: looking for biomarkers.","volume":"45","author":"Krzyszto\u00f1-Russjan","year":"2013","journal-title":"J Bioenerg Biomembr."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1091\/mbc.11.5.1919","article-title":"Branched chain amino acids induce apoptosis in neural cells without mitochondrial membrane depolarization or cytochrome c release: implications for neurological impairment associated with maple syrup urine disease.","volume":"11","author":"Jouvet","year":"2000","journal-title":"Mol Biol Cell."},{"key":"B74","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1093\/hmg\/ddu123","article-title":"Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders.","volume":"23","author":"Burrage","year":"2014","journal-title":"Hum Mol Genet."},{"key":"B75","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.bbadis.2016.01.016","article-title":"Mitochondrial response to the BCKDK-deficiency: some clues to understand the positive dietary response in this form of autism.","volume":"1862","author":"Oyarzabal","year":"2016","journal-title":"Biochim Biophys Acta."},{"key":"B76","doi-asserted-by":"publisher","first-page":"20583","DOI":"10.1074\/jbc.M114.569251","article-title":"Benzothiophene carboxylate derivatives as novel allosteric inhibitors of branched-chain \u03b1-ketoacid dehydrogenase kinase.","volume":"289","author":"Tso","year":"2014","journal-title":"J Biol Chem."},{"key":"B77","doi-asserted-by":"publisher","first-page":"9728","DOI":"10.1073\/pnas.1303220110","article-title":"Structure-based design and mechanisms of allosteric inhibitors for mitochondrial branched-chain \u03b1-ketoacid dehydrogenase kinase.","volume":"110","author":"Tso","year":"2013","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.647481","article-title":"Pyridostigmine protects against diabetic cardiomyopathy by regulating vagal activity. Gut microbiota, and branched-chain amino acid catabolism in diabetic mice.","volume":"12","author":"Yang","year":"2021","journal-title":"Front Pharmacol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.metabol.2018.09.007","article-title":"PPAR\u03b3 is a major regulator of branched-chain amino acid blood levels and catabolism in white and brown adipose tissues.","volume":"89","author":"Blanchard","year":"2018","journal-title":"Metabolism."},{"key":"B80","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.metabol.2015.01.008","article-title":"Effect of insulin sensitizer therapy on amino acids and their metabolites.","volume":"64","author":"Irving","year":"2015","journal-title":"Metabolism."},{"key":"B81","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.orcp.2015.01.003","article-title":"Elevation of branched-chain amino acid levels in diabetes and NAFL and changes with antidiabetic drug treatment.","volume":"9","author":"Iwasa","year":"2015","journal-title":"Obes Res Clin Pract."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.932670\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T01:42:59Z","timestamp":1658108579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.932670\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,18]]},"references-count":81,"alternative-id":["10.3389\/fnut.2022.932670"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.932670","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,18]]},"article-number":"932670"}}