Branched-chain Amino Acid Oxidation in Skeletal Muscle – Physiological and Clinical Importance of its Modulation by Reactant Availability

Abstract

Enhanced oxidation of branched-chain amino acids (BCAA; valine, leucine and isoleucine) in skeletal muscle is a typical metabolic alteration associated with activated synthesis of glutamine and development of muscle wasting in cachectic illness. The paper demonstrates that the rates of BCAA transamination and decarboxylation in skeletal muscle respond rapidly to changes in BCAA and glutamine availability. Enhanced BCAA availability increases BCAA oxidation and glutamine synthesis, while enhanced availability of glutamine suppresses BCAA oxidation. In physiological conditions, this enables compensation in alterations of amount and composition of food in order to keep optimal levels of BCAA and glutamine in the body. In cachectic illness, enhanced availability of BCAA (resulting mainly from activated proteolysis) and decreased availability of glutamine (resulting from its enhanced release by muscle) account significantly for activated BCAA oxidation and glutamine synthesis in muscle. The clinical importance of the opposite effect of BCAA and glutamine supplementation on BCAA oxidation in the treatment of muscle wasting disorders should be elucidated.

Acute effects of phenylbutyrate on glutamine, branched‐chain amino acid and protein metabolism in skeletal muscles of rats

“…Some articles indicate associations between BCAA and protein metabolism in muscle (O'Donnel et al . ; Holecek ) and, therefore, the differences in BCAA and GLN metabolism induced by PB in SOL and EDL may play a role in different alterations in protein metabolism. The findings of more pronounced effects of PB in EDL (composed predominantly of white, fast‐twitch fibres) compared with SOL (composed predominantly of red, slow‐twitch fibres) is a further evidence of higher sensitivity of fast‐twitch fibres to various signals than slow‐twitch fibres as reported in number of other articles (Kadlcikova et al .…”

“…In this connection, it should be noted that the effects of PB on leucine oxidation and GLN concentration in muscles were more pronounced in EDL and the decrease in BCAA concentrations in incubation medium after addition of PB was observed only in medium with EDL. Some articles indicate associations between BCAA and protein metabolism in muscle (O'Donnel et al 1976;Holecek 2011) and, therefore, the differences in BCAA and GLN metabolism induced by PB in SOL and EDL may play a role in different alterations in protein metabolism. The findings of more pronounced effects of PB in EDL (composed predominantly of white, fast-twitch fibres) compared with SOL (composed predominantly of red, slowtwitch fibres) is a further evidence of higher sensitivity of fast-twitch fibres to various signals than slow-twitch fibres as reported in number of other articles (Kadlcikova et al 2004;Muthny et al 2008Muthny et al , 2009).…”

The Complex Role of Branched Chain Amino Acids in Diabetes and Cancer

“…The enzymes BCAA aminotransferase (BCAAAT), alanine aminotransferase (ALT) and glutamine synthetase (GLNS) are all reversible and near equilibrium and thus any changes in substrate availability (e.g., BCAAs, alanine, glutamine, glutamate and α-ketoglutarate) results in a change in enzyme activities, including the oxidation of the BCKAs. Studies have shown that enhanced supplies of BCAAs will increase the oxidative pathway along with the release of resultant alanine and glutamine [ 29 , 30 , 31 ]. Conversely, enhanced supply of glutamine was shown to reduce the activity of the oxidative pathway.…”

Branched-chain amino acids and ammonia metabolism in liver disease: Therapeutic implications

“…Therefore, it is reasonable to suppose that by increasing BCAA intake, GLN synthesis and BCAA catabolism in skeletal muscle, and consequently ammonia production in the gut and kidneys, is activated. Increased BCAA catabolism in skeletal muscle proportional to their intake has been shown in a number of articles [59][60][61]. Unfortunately, there are no valid measures to determine adequacy or excess of BCAA intake that can guide their therapeutic use.…”