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Review
. 2022 Apr 5;23(7):4022.
doi: 10.3390/ijms23074022.

The Critical Role of the Branched Chain Amino Acids (BCAAs) Catabolism-Regulating Enzymes, Branched-Chain Aminotransferase (BCAT) and Branched-Chain α-Keto Acid Dehydrogenase (BCKD), in Human Pathophysiology

Aikaterini Dimou  1 , Vasilis Tsimihodimos  2 , Eleni Bairaktari  1
Affiliations
Review

The Critical Role of the Branched Chain Amino Acids (BCAAs) Catabolism-Regulating Enzymes, Branched-Chain Aminotransferase (BCAT) and Branched-Chain α-Keto Acid Dehydrogenase (BCKD), in Human Pathophysiology

Aikaterini Dimou et al. Int J Mol Sci. .

Abstract

Branched chain amino acids (BCAAs), leucine, isoleucine and valine, are essential amino acids widely studied for their crucial role in the regulation of protein synthesis mainly through the activation of the mTOR signaling pathway and their emerging recognition as players in the regulation of various physiological and metabolic processes, such as glucose homeostasis. BCAA supplementation is primarily used as a beneficial nutritional intervention in chronic liver and kidney disease as well as in muscle wasting disorders. However, downregulated/upregulated plasma BCAAs and their defective catabolism in various tissues, mainly due to altered enzymatic activity of the first two enzymes in their catabolic pathway, BCAA aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKD), have been investigated in many nutritional and disease states. The current review focused on the underlying mechanisms of altered BCAA catabolism and its contribution to the pathogenesis of a numerous pathological conditions such as diabetes, heart failure and cancer. In addition, we summarize findings that indicate that the recovery of the dysregulated BCAA catabolism may be associated with an improved outcome and the prevention of serious disease complications.

Keywords: BCKAs; T2DM; cancer; catabolic enzymes; catabolism; heart failure; isoleucine; leucine; valine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) BCAA catabolism. (B) An alternative pathway of leucine catabolism in the cytosol of the liver.
Figure 2
Figure 2
(A) BCKD complex. (B) Regulation of the BCKD complex.
Figure 3
Figure 3
Activation of mTORC1 by leucine.
Figure 4
Figure 4
(A) L-alloisoleucine formation. (B) Solotone formation in MSUD.
Figure 5
Figure 5
Causes of the (↑) increased BCAAs in obesity, IR and T2DM.
Figure 6
Figure 6
Association between the altered BCAA catabolism in adipose tissue and skeletal muscle with IR (↓ downregulated; ↑ upregulated).
See this image and copyright information in PMC

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