Renal amino acid transport: cellular and molecular events from clearance studies to frog eggs.
This article reviews recent advances in the mechanisms of renal amino acid transport. Renal amino acid transport is necessary to efficiently reclaim approximately 450 mmol amino acids from the glomerular ultrafiltrate each day in man. In general, individual amino acids are transported across the epithelial membrane of the proximal tubule by a sodium (Na+) dependent mechanism. This cotransport process utilizes the energy of the Na+ gradient to enter the cell. The amino acid then exits the basolateral surface and Na+ is pumped out by the Na(+)-K(+)-ATPase located in the basolateral membrane. In addition to the cellular accumulation of amino acids across the luminal membrane, these compounds may be taken up by the cell from the basolateral surface. Most amino acids are transported both individually and in a series of seven group specific processes. Human disorders of amino acid transport have been described for six of the seven transport systems. The process of ontogeny of amino acid accumulation by the proximal tubule is a complex one and will be further discussed in this review. A number of factors including pH, ion dependency, electrogenicity of transport process, as well as a variety of hormonal factors, may contribute to the regulation of amino acid transport. Gene expression of several amino acid transporters has been successfully performed using the oocyte of the frog Xenopus laevis. Using this system, a number of transporters have been cloned. Such a strategy will permit the cloning of virtually all transporter molecules, and thus we can anticipate the elucidation of the structure of the transporters. However, for a comprehensive understanding of cytoskeletal interactions protein phosphorylation and phospholipid domains and their linkage to the primary structure of the transporter need to be studied. The future for research in this area is indeed a bright one.
Chesney
R W
RW
Department of Pediatrics, University of Tennessee, Memphis College of Medicine.
Jones
D
D
Zelikovic
I
I
D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D015394:Molecular Structure; D009865:Oocytes / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D014982:Xenopus laevis
D000596:Amino Acids; D002352:Carrier Proteins; D012964:Sodium