Branched-Chain Amino Acids Activate Key Enzymes in Protein Synthesis after Physical Exercise

Abstract

BCAAs (leucine, isoleucine, and valine), particularly leucine, have anabolic effects on protein metabolism by increasing the rate of protein synthesis and decreasing the rate of protein degradation in resting human muscle. Also, during recovery from endurance exercise, BCAAs were found to have anabolic effects in human muscle. These effects are likely to be mediated through changes in signaling pathways controlling protein synthesis. This involves phosphorylation of the mammalian target of rapamycin (mTOR) and sequential activation of 70-kD S6 protein kinase (p70 S6 kinase) and the eukaryotic initiation factor 4E-binding protein 1. Activation of p70 S6 kinase, and subsequent phopsphorylation of the ribosomal protein S6, is associated with enhanced translation of specific mRNAs. When BCAAs were supplied to subjects during and after one session of quadriceps muscle resistance exercise, an increase in mTOR, p70 S6 kinase, and S6 phosphorylation was found in the recovery period after the exercise with no effect of BCAAs on Akt or glycogen synthase kinase 3 (GSK-3) phosphorylation. Exercise without BCAA intake led to a partial phosphorylation of p70 S6 kinase without activating the enzyme, a decrease in Akt phosphorylation, and no change in GSK-3. It has previously been shown that leucine infusion increases p70 S6 kinase phosphorylation in an Akt-independent manner in resting subjects; however, a relation between mTOR and p70 S6 kinase has not been reported previously. The results suggest that BCAAs activate mTOR and p70 S6 kinase in human muscle in the recovery period after exercise and that GSK-3 is not involved in the anabolic action of BCAAs on human muscle.

Expression of growth-related genes in young and older human skeletal muscle following an acute stimulation of protein synthesis

“…REDD2 and its paralog REDD1 have been identified as negative regulators of mTOR (17), possibly through the control of the TSC1/2 complex (18). Thus a decrease in REDD2 mRNA expression is consistent with an activation of mTOR signaling following an anabolic stimulus (9,(21)(22)(23)30). The decrease in REDD2 mRNA during the recovery from this potent anabolic stimulus is in agreement with an increase in mTOR phosphorylation and elevated rates of protein synthesis in these same subjects (23).…”

Resistance exercise with whey protein ingestion affects mTOR signaling pathway and myostatin in men

“…The most important component responsible for the increased phosphorylation of p70 S6K with the whey protein ingestion is probably its large content of branched-chain amino acids that can elicit a similar p70 S6K response in the context of a bout of RE as observed in the present study (3,26). S6K1/p70 S6K has been shown in animal and cell models to be especially important in muscle hypertrophy (2,40,48).…”

Plasma Biomarkers of Poor Muscle Quality in Older Men and Women from the Baltimore Longitudinal Study of Aging

“…Branched chain amino acids (BCAA, leucine, isoleucine, and valine) account for 35% of the essential amino acids found in muscle proteins (27,28). While the degradation of most amino acids occurs in the liver, BCAA are mostly metabolized in muscle tissue by mitochondrial dehydrogenase and branch-chain ketoacid dehydrogenase to produce the branch-chain keto acids (29).…”

“…While the degradation of most amino acids occurs in the liver, BCAA are mostly metabolized in muscle tissue by mitochondrial dehydrogenase and branch-chain ketoacid dehydrogenase to produce the branch-chain keto acids (29). The generated ketoacids are used by the muscle to generate ATP via the Kreb's cycle or transported to the liver for oxidation (27,28). Studies have suggested that muscle protein synthesis is upregulated by amino acids with leucine being the most potent (30,31).…”