Branched Chain Amino Acids Isoleucine Leucine Valine

Branched chain amino acids (BCAAs) are essential amino acids, which together compose approximately a third of the daily amino acid requirement in humans. BCAAs, and especially leucine, play an important role in the regulation of energy and protein metabolism. BCAAs are primarily oxidized in skeletal muscle and not in the liver. BCAAs donate their amino groups to furnish glutamic acid in muscle in transamination reactions yielding the a-ketoa-cids a-ketoisocaproic acid, a-keto-^-methylvaleric acid, and a-ketoisovaleric acid. These transamination products of BCAAs can enter the citrate cycle and contribute to ATP production by aerobic substrate oxidation, which is important during the change from rest to exercise. After consumption of protein-containing meals, a large part of the BCAA passes through the liver and is taken up by muscle where it primarily contributes to protein synthesis and the synthesis of glutamine, which accounts for about 70% of the amino acid release from muscle. The importance of the essential branched chain amino acids for protein synthesis is strikingly exemplified by the negative nitrogen balance and catabo-lism that follows upper gastrointestinal bleeding caused by ingestion of large amounts of hemoglobin (which lacks isoleucine). Leucine has been suggested to regulate the turnover of protein in muscle cells by inhibiting protein degradation and enhancing protein synthesis. This has led to a worldwide interest in the possible use of BCAAs in general, and leucine in particular, for metabolic support.

In liver failure the plasma concentrations of the aromatic amino acids (AAAs) tyrosine, phenylala-nine, and tryptophan increase, probably because they are predominantly broken down in the liver, whereas the plasma levels of BCAAs decrease while they are degraded in excess in muscle as a consequence of hepatic failure-induced catabolism. As AAAs and BCAAs are all neutral amino acids and share a common transporter across the blood-brain barrier (system L carrier), changes in their plasma ratio are reflected in the brain, subsequently disrupting the neurotransmitter profile of the catecholamines and indoleamines (see sections on tyrosine and tryptophan). It has been hypothesized that this disturbance contributes to the multi-factorial pathogenesis of hepatic encephalopathy. In line with this hypothesis it has been suggested that normalization of the amino acid pattern by supplementing extra BCAAs counteracts hepatic encephalopathy.

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