Interorgan Amino Acid Transport and its Regulation

Abstract

Interorgan amino acid transport is a highly active and regulated process that provides amino acids to all tissues of the body, both for protein synthesis and to enable amino acids to be used for specific metabolic functions. It is also an important component of plasma amino acid homeostasis. Net movement of amino acids depends on the physiological and nutritional state. For example, in the fed state the dominant flux is from the intestine to the other tissues. In starvation the dominant flux is from muscle to the liver and kidney. A number of general principles underlie many amino acid fluxes: i) The body does not have a store for amino acids. This means that dietary amino acids, in excess of those required for protein synthesis, are rapidly catabolized; ii) Amino acid catabolism must occur in a manner that does not elevate blood ammonia. Thus, extrasplanchnic amino acid metabolism often involves an innocuous means of transporting nitrogen to the liver; iii) Because most amino acids are glucogenic, there will be a considerable flux of amino acids to the gluconeogenic organs when there is a need to produce glucose. In addition to these bulk flows, fluxes of many specific amino acids underlie specific organ function. These include intestinal oxidation of enteral amino acids, the intestinal/renal axis for arginine production, the brain uptake of neurotransmitter precursors and renal glutamine metabolism. There is no single means of regulating amino acid fluxes; rather, such varied mechanisms as substrate supply, enzyme activity, transporter activity and competitive inhibition of transport are all found.

Molecular mechanisms of glutamine action

“…The L-alanine produced in the intestinal epithelial cell pathway is exported to the hepatic portal vein for transport to the liver Brosnan, 2003;Newsholme et al, 2003b).…”

Amino Acid Metabolism, β-Cell Function, and Diabetes

“…Depolarization of the plasma membrane will then result in activation of voltagedependent calcium channels, an increase in cytosolic Ca 2ϩ , and subsequent stimulation of insulin secretion. Clinical assessment of administered L-arginine has revealed only limited beneficial effects, possibly due to rapid removal of the amino acid in the epithelial cells of the intestine, where it can be rapidly converted to ornithine and citrulline, then exported to the kidney (71) or the liver, where it can be converted to proline for export (71).…”

Reduced Glutamatergic Neurotransmission as Possible Indicator of Unfavorable Prognosis

“…[31] According to B.Bein and A. Ezhova, [32] the constant maintenance of a certain amount of free AAs in the blood is carried out due to transfer from the gastrointestinal tract and tissue during protein decay, as well as redistribution and consumption of AAs in organs and tissues. The exact mechanisms that lead to a change in the plasma Glu levels remain unknown, but in general, it is release and redistribution of Glu between organs or the activation of neutralizing natural mechanisms.…”