Novel metabolic and physiological functions of branched chain amino acids: a review

Abstract

It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including: (1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis. (2) BCAA, especially isoleucine, play a major role in enhancing glucose consumption and utilization by up-regulating intestinal and muscular glucose transporters. (3) Supplementation of leucine in the diet enhances meat quality in finishing pigs. (4) BCAA are beneficial for mammary health, milk quality and embryo growth. (5) BCAA enhance intestinal development, intestinal amino acid transportation and mucin production. (6) BCAA participate in up-regulating innate and adaptive immune responses. In addition, abnormally elevated BCAA levels in the blood (decreased BCAA catabolism) are a good biomarker for the early detection of obesity, diabetes and other metabolic diseases. This review will provide some insights into these novel metabolic and physiological functions of BCAA.

Keywords: Amino acid transporters; Glucose transporters; Gut health; Immunity; Lipolysis; Mammary health; Meat quality; Milk production.

Fig. 1

Pathway of branched chain amino acid catabolism. BCAA are catabolized to acetyl-CoA and/or succinate-CoA and subsequently enter the TCA cycle. The main steps of the catabolic reactions (transamination by BCAT and decarboxylation by BCKD) are shown. With the help of BCAT, BCAA are catabolized into branched-chain α-ketoacids which are subsequently decarboxylated by BCKD. Finally, all the BCAA metabolites are catabolized by a series of enzyme reactions to final products and enter the TCA cycle

Fig. 2

Isoleucine up-regulates intestinal and muscular transporters. GLUT1 and GLUT4 are vital glucose transporters in muscle. SGLT1 and GLUT2 are important glucose transporters in the small intestine. Isoleucine could potentially increase muscle growth and intestinal development and health by up-regulating the protein expression of GLUT1 and GLUT4 in muscle and enhancing the expression of SGLT1 and GLUT2 in the small intestine

Fig. 3

Leucine increases protein synthesis by activation of the mTOR signaling pathway. Leucine enhanced muscle synthesis via the mammalian target of rapamycin (mTOR) pathway leading to phosphorylation of its downstream target proteins, eukaryotic initiation factor 4E-binding protein (4E-BP1) and p70 ribosomal S6 kinase 1 (S6K1). Under unphosphorylated conditions, 4EBP1 tightly binds to eIF4E, forming the inactive eIF4E · 4EBP1 complex. During anabolic conditions, mTORC1 induces the phosphorylation of 4EBP1, resulting in the dissociation of eIF4E from the inactive complex and allowing eIF4E to form an active complex with eIF4G. The process of association of eIF4E with eIF4G is obligatory for the binding of the 43S pre-initiation complex with mRNA. S6K1 is another mTORC1 substrate that participates in the regulation of mRNA translation. This kinase plays an important role in the regulation of terminal oligopyrimidine mRNA which is responsible for the translation of proteins involved in the protein synthetic apparatus

Fig. 4

Branched chain amino acids regulate mammary function and embryo development. BCAA play a vital role in mammary function and embryo development mainly in the synthesis of other conditional amino acids and activation of the mTOR signaling pathway