Leucine is a branched chain amino acid that shows anti-catabolic properties in humans. Leucine, along with the other branched chain amino aids isoleucine and valine, account for roughly 15% of the amino acids found in muscle tissue. Leucine is though to prevent catabolism of muscle tissue because it is able to stimulate protein synthesis using the insulin signalling pathway via mTOR kinase. Leucine appears to offer particular benefits during exercise, when skeletal muscle catabolism increases to facilitate the conversion of structural muscle components into energy. This process allows the sparing of pyruvate, which is converted to lactate and exported to the liver to maintain blood sugar levels through gluconeogenesis. Ingestion of dietary leucine at this time is thought to prevent the oxidation of leucine in muscle tissue and inhibit muscle protein breakdown.
A number of leucine metabolites are also thought to possess similar anti-catabolic effects on muscle tissue. Of these α-ketoisocaproate (KIC) and β-hydroxy-β-methylbuterate (HMB) have both been extensively researched with regard to their anti-catabolic effects. The metabolite KIC is produced from leucine via the enzyme branched chain amino transferase. Once formed, KIC can then be subsequently converted to HMB via the cytosolic enzyme KIC dioxygenase (requires iron and molecular oxygen). There is also a mitochondrial enzyme KIC dehydrogenase that can convert KIC to isovaleryl CoA. The cytosolic KIC dioxygenase is present in large amounts in the liver where it has a 20 fold higher Km for KIC than the mitochondrial dehydrogenase, suggesting that it is active only at very high plasma levels of substrate and therefore liver HMB production is controlled by plasma KIC concentrations.
From animal studies it has been suggested that round 5% of the leucine metabolism occurs through the cytosolic liver dioxygenase enzyme. Extrapolated to an average size human male, liver production of HMB would be around 0.2 g/d at lower intakes of dietary leucine. As dietary intakes of leucine increased, this figure may be expected to rise to around 0.4 g/d. Intakes of leucine in the region of 20 to 50 g/d would be required to raise liver production of HMB to the gram amounts. Researchers1 has investigated the effects of intakes of gram amounts of the leucine metabolite HMB on the metabolism of muscle tissue during resistance training The results showed that HMB was able to significantly decrease the rise in muscle catabolism associated with resistance training, and increase fat free mass when compared to a placebo.
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