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Review
. 2022 Jul 18:9:932670.
doi: 10.3389/fnut.2022.932670. eCollection 2022.

The Role of Branched-Chain Amino Acids and Branched-Chain α-Keto Acid Dehydrogenase Kinase in Metabolic Disorders

Chuang Du  1   2   3   4 , Wen-Jie Liu  1   2   3 , Jing Yang  1   2   3 , Shan-Shan Zhao  1   2   3   5 , Hui-Xin Liu  1   2   3
Affiliations
Review

The Role of Branched-Chain Amino Acids and Branched-Chain α-Keto Acid Dehydrogenase Kinase in Metabolic Disorders

Chuang Du et al. Front Nutr. .

Abstract

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 α-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.

Keywords: MALDI-MSI; branched-chain amino acids; branched-chain α-keto acid dehydrogenase kinase; metabolic disorders; microbiota.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Most of the BCAAs come from protein decomposition and food absorption. The reversible transamination reaction of BCAAs catabolism mostly occurs in skeletal muscle. After BCKAs are released back into circulation, most of them are oxidatively decarboxylated to acyl-CoA in the liver.
FIGURE 2
FIGURE 2
A brief schematic of BCKA catabolism, and the enzymes that regulate this process.
FIGURE 3
FIGURE 3
Role of BCAAs metabolism in health. Abnormal elevation or deficiency of BCAAs lead to many diseases, such as neurobehavioral deficits, heart failure, T2DM and obesity.
See this image and copyright information in PMC

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References

    1. Neinast M, Murashige D, Arany Z. Branched chain amino acids. Annu Rev Physiol. (2019) 81:139–64. 10.1146/annurev-physiol-020518-114455 - DOI - PMC - PubMed
    1. Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol. (2014) 10:723–36. 10.1038/nrendo.2014.171 - DOI - PMC - PubMed
    1. White PJ, Newgard CB. Branched-chain amino acids in disease. Science. (2019) 363:582–3. 10.1126/science.aav0558 - DOI - PMC - PubMed
    1. Holeèek M. Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements. Nutr Metab. (2018) 15:33. 10.1186/s12986-018-0271-1 - DOI - PMC - PubMed
    1. Shin AC, Fasshauer M, Filatova N, Grundell LA, Zielinski E, Zhou JY, et al. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism. Cell Metab. (2014) 20:898–909. 10.1016/j.cmet.2014.09.003 - DOI - PMC - PubMed