Amino Acid Transport in Liver

The Effects of Hypoxia-Ischemia on Neutral Amino Acid Transporters in the Developing Rat Brain

“…Furthermore, the levels of glutamine increase after HI [16] . In addition to its role as a precursor for glutamate, glutamine may function in cellular energy demand and a carrier/donor of carbon and nitrogen atoms [17,18] . SNAT1 is a low-affinity (K m 489 M ), high-capacity transporter of glutamine and would be an ideal candidate to transport increased amounts of glutamine seen after HI [6] .…”

Hepatic Glutamine Transport and Metabolism

“…These studies suggested that a 100-kDa plasma membrane protein mediates system N transport activity in rat hepatocytes (Tamarappoo et al, 1992). In studies on the initial rate of glutamine uptake into either whole cells (Kilberg et al, 1980, Fafournoux et al, 1983 or mitochondria (Kovacevic and Bajin 1982), glutamine influx and efflux rates far above the known rates of metabolic glutamine turnover were found. This led to the generally 46 DIETER HAUSSINGER accepted view that glutamine transport across biological membranes in the liver is not controlling its metabolism.…”

“…Ammonia activation of glutamine breakdown in the perfused rat liver is maximal at NH$ concentrations of 0.6 mM and is half-maximal at 0.2-0.3 mM, that is, at the physiological portal ammonia concentration (Haussinger and Sies, 1979). Because ammonia is generated in the intestine, an interorgan feed-forward system for hepatic glutamine metabolism has been proposed (Haussinger, 1979;Welbourne, 1987). When glutamine is infused at high concentrations of 5 mM in single pass perfused rat liver, glutamine breakdown occurs only after a lag phase of about 30 min, which is required for full self-activation of the enzyme by its reaction product ammonia.…”

“…This lag phase can be shortened by a brief pulse of ammonia in order to activate the enzyme and to perpetuate activation by the ammonia formation during glutamine breakdown . Lowering the pH inhibits glutamine breakdown (Lueck and Miller, 1970;Haussinger et al, 1980;Haussinger et al, 1983, whereas alkalosis stimulates. Inhibition of flux through glutaminase at low pH is due to an increased concentration of ammonium ions required for activation of glutarninase (Verhoeven et al, 1983), but also due to an inhibition of glutamine transport across the plasma and mitochondrial membrane (Lenzen et al, 1987).…”

“…PLASMA MEMBRANE TRANSPORT Glutamine is transported across the plasma membrane and the inner-mitochondrial membrane by specific transport systems (for reviews see McGivan, 1983,1984). Two transport systems in the plasma membrane have been described: the Na+ -dependent transport system "N" (Kilberg et d., 1980) and a Na+-independent system, which is probably involved in facilitated diffusion of glutamine from hepatocytes (Fafournoux et al, 1983). This latter export system has recently been designated "system n" ; it is upregulated in the tumor-bearing rat and is down regulated by glutamine under these conditions (Inoue et al, 1995).…”