The Complex Pattern of Muscle Amino Acid Catabolism and Release Is Necessary to Accommodate the Liver's Limited Capacity for Uptake of Branch-Chain Amino Acids and to Facilitate the Removal of Amino Nitrogen from the Muscle
It might appear that a simpler system of amino acid transfer to the liver would suffice. Why are amino acids not just released from muscle cell amino acid pools into the blood and transported to the liver for glucose synthesis? The answer lies in the limited uptake capacity of the liver for BCAAs and the need to transport amino nitrogen out of the muscle.
BCAAs, the predominant amino acids of skeletal muscle, are not taken up readily by the liver; thus, if BCAAs were not transformed to alanine, amino acid transfer to the liver would be limited.In addition, alanine is a convenient means by which nitrogen from the deamination of muscle amino acid can be transported to the liver. This is important because free amino groups
FIGURE 32-14 Alanine arising from BCAA catabolism in muscle is converted to glucose and urea in the IivenThe glucose produced can potentially return to the muscle for alanine production.Thus the cycle of alanine to glucose forms a shuttle to transport nitrogen from the muscle to the liver for urea synthesis. NH3, Ammonia.
liberated by the catabolism of amino acids in muscle, if not removed, could lead to the formation of toxic levels of ammonia. Ammonia is detoxified in the body by the formation of urea, but urea formation occurs only in the liver. Thus, alanine forms a gluconeogenic precursor that also transports nitrogen to the liver for urea synthesis. Figures 32-13 and 32-14 illustrate the role of alanine in the transport of amino acid nitrogen and carbon to the liver for synthesis of urea and glucose, respectively.
The regulation of muscle protein mobilization is influenced to a large extent by the lack of insulin. However, the adrenocortical hormone cortisol has an important effect of stimulating protein breakdown and amino acid mobilization. Through the mobilization of muscle protein and stimulation of hepatic gluconeogenesis, cortisol exerts one of its major effects, raising blood glucose concentration. Under normal conditions, glucagon, the other major gluconeogenic hormone, exerts its effects on the liver and does not appear to have a direct effect on muscle.