Protein and amino acid metabolism in human muscle.

Muscle proteins turn over slowly and there are minimal diurnal changes in the size of the muscle protein pool in response to feeding and fasting. Nitrogen balance and tracer studies indicate that protein oxidation and net protein breakdown (degradation--synthesis) is not increased during dynamic exercise at intensities of < or = 70% VO2max. An imbalance between muscle protein synthesis and degradation does exist during one leg knee extensor exercise and during two legged cycling in patients with glycogen phosphorylase deficiency. In these latter cases amino acids liberated from the protein pool are used for synthesis of TCA-cycle intermediates and glutamine. Six amino acids are metabolized in resting muscle: leucine, isoleucine, valine, asparagine, aspartate and glutamate. Only leucine and part of the isoleucine molecule can be converted to acetylCoA and oxidized. The carbon skeleton of the other amino acids is used for synthesis of TCA-cycle intermediates and glutamine. The six amino acids provide the amino groups and the ammonia for synthesis of glutamine and alanine, which are released by muscle in excessive amounts. About half of the glutamine release from muscle originates from glutamate taken up from the blood. Glutamine produced by muscle is an important fuel and regulator of DNA and RNA synthesis in mucosal cells and immune system cells and fulfils several other important functions in human metabolism. The alanine aminotransferase reaction functions to establish and maintain high concentrations of TCA-cycle intermediates and a high TCA cycle flux in the first minutes of exercise. A gradual increase in leucine oxidation subsequently leads to a carbon drain on the TCA-cycle in glycogen depleted muscles and may thus reduce the maximal flux in the TCA-cycle and lead to fatigue. Deamination of amino acids and glutamine synthesis present alternative anaplerotic mechanisms in glycogen depleted muscles but only allow exercise at 40-50% of Wmax. It is proposed that the maximal flux in the TCA-cycle is reduced in glycogen depleted muscles due to insufficient TCA-cycle anaplerosis and that this presents a limitation for the maximal rate of fatty acid oxidation. Interactions between the amino acid pool and the TCA-cycle thus seem to play a central role in the energy metabolism of the exercising muscle.