Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements

Abstract

Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are essential amino acids with protein anabolic properties, which have been studied in a number of muscle wasting disorders for more than 50 years. However, until today, there is no consensus regarding their therapeutic effectiveness.In the article is demonstrated that the crucial roles in BCAA metabolism play: (i) skeletal muscle as the initial site of BCAA catabolism accompanied with the release of alanine and glutamine to the blood; (ii) activity of branched-chain keto acid dehydrogenase (BCKD); and (iii) amination of branched-chain keto acids (BCKAs) to BCAAs. Enhanced consumption of BCAA for ammonia detoxification to glutamine in muscles is the cause of decreased BCAA levels in liver cirrhosis and urea cycle disorders. Increased BCKD activity is responsible for enhanced oxidation of BCAA in chronic renal failure, trauma, burn, sepsis, cancer, phenylbutyrate-treated subjects, and during exercise. Decreased BCKD activity is the main cause of increased BCAA levels and BCKAs in maple syrup urine disease, and plays a role in increased BCAA levels in diabetes type 2 and obesity. Increased BCAA concentrations during brief starvation and type 1 diabetes are explained by amination of BCKAs in visceral tissues and decreased uptake of BCAA by muscles.The studies indicate beneficial effects of BCAAs and BCKAs in therapy of chronic renal failure. New therapeutic strategies should be developed to enhance effectiveness and avoid adverse effects of BCAA on ammonia production in subjects with liver cirrhosis and urea cycle disorders. Further studies are needed to elucidate the effects of BCAA supplementation in burn, trauma, sepsis, cancer and exercise. Whether increased BCAA levels only markers are or also contribute to insulin resistance should be known before the decision is taken regarding their suitability in obese subjects and patients with type 2 diabetes.It is concluded that alterations in BCAA metabolism have been found common in a number of disease states and careful studies are needed to elucidate their therapeutic effectiveness in most indications.

A Quantitative Proteome Map of the Human Body

“…4E). Multiple studies have shown that the first step of BCAA metabolism mainly takes place in skeletal muscle due to the high activity of BCAT2 (31,33). However, our data showed that BCAT2 is not enriched in skeletal muscle and its RNA level is relatively low as well (Fig.…”

“…They serve as substrates for protein synthesis or energy production and perform several metabolic and signaling functions as well. The tissue specific distribution of the BCAA metabolic enzymes, especially for the first two steps, determines the unique inter-organ BCAA metabolite shuttling (31,32). In our study, most of the key enzymes involved in BCAA metabolism have been observed.…”

Dietary restriction of amino acids for Cancer therapy

“…Interestingly, EAAs may ideally act as a key signal for amino acid availability. Specifically, leucine is one of branched chain AAs (BCAAs), which are not first catabolized in the liver due to the low activity of BCAA aminotransferase [22]. Consequently, leucine increases rapidly in circulation after meal [22], and are readily available as an essential nutritional signal to reduce food intake via mTOR-dependent inhibition of hypothalamic Agoutirelated protein (Agrp) gene expression [23,24].…”

Ketogenic diets and protective mechanisms in epilepsy, metabolic disorders, cancer, neuronal loss, and muscle and nerve degeneration

“…Moreover, owing to aberrant mitochondrial functioning and reduced enzyme activity for ketone consumption, cancer cells fail to metabolize ketone bodies, necessitating the supply of a fat rich, low‐carbohydrate diet to induce ketosis (Morscher et al, ). The process typically comprises supplementation with eicosapentaenoic acid and branched chain amino acids that promote anabolism and suppress cellular catabolism, associated with an enhanced lean body mass (Holecek, ). The beneficial impact of KD on tumor growth and proliferation as well as longevity has been observed to be greater under calorie‐restricted regimens, rather than ad libitum treatment that blocked circulating glucose reduction (Weber, Aminazdeh‐Gohari, & Kofler, ).…”

“…Moreover, owing to aberrant mitochondrial functioning and reduced enzyme activity for ketone consumption, cancer cells fail to metabolize ketone bodies, necessitating the supply of a fat rich, low-carbohydrate diet to induce ketosis (Morscher et al, 2015). The process typically comprises supplementation with eicosapentaenoic acid and branched chain amino acids that promote anabolism and suppress cellular catabolism, associated with an enhanced lean body mass (Holecek, 2018).…”