Rat liver endothelial cell glutamine transporter and glutaminase expression contrast with parenchymal cells

Abstract

Despite the central role of the liver in glutamine homeostasis in health and disease, little is known about the mechanism by which this amino acid is transported into sinusoidal endothelial cells, the second most abundant hepatic cell type. To address this issue, the transport ofl-glutamine was functionally characterized in hepatic endothelial cells isolated from male rats. On the basis of functional analyses, including kinetics, cation substitution, and amino acid inhibition, it was determined that a Na+-dependent carrier distinct from system N in parenchymal cells, with properties of system ASC or B0, mediated the majority of glutamine transport in hepatic endothelial cells. These results were supported by Northern blot analyses that showed expression of the ATB0 transporter gene in endothelial but not parenchymal cells. Concurrently, it was determined that, whereas both cell types express glutamine synthetase, hepatic endothelial cells express the kidney-type glutaminase isozyme in contrast to the liver-type isozyme in parenchymal cells. This represents the first report of ATB0 and kidney-type glutaminase isozyme expression in the liver, observations that have implications for roles of specific cell types in hepatic glutamine homeostasis in health and disease.

Effect of Fasting on the Metabolic Response of Liver to Experimental Burn Injury

“…Among the amino acids found to be significantly affected in this study are glutamine and arginine, both of which have been reported to be either beneficial or “conditionally essential” after burn injury [7], [37], [38]. This is also consistent with prior findings of burn injury-induced increases in the expression of amino acid transporters for glutamine and arginine in the liver [8], [39], [40]. Glycine and methionine were also upregulated, and therefore may be potential candidates to further examine as nutritional supplements.…”

Flexibility of the hepatic zonation of carbon and nitrogen fluxes linked to lactate and pyruvate transformations in the presence of ammonia

“…2 summarizes the main pathways leading to the production of the metabolites that were measured in the present work. These cells are able to express glutamine synthetase (18), which is also found in Kupffer and endothelial cells (4,29). Enzyme gradients along the hepatic acinus, however, are not represented.…”

Endothelial Cell Metabolism in Normal and Diseased Vasculature

“…Glutamine has the added value to contribute both its carbons and nitrogens to ECs’ metabolism (though the relative importance of both in vessel sprouting remains to be determined) and can therefore serve different, mostly biosynthetic metabolic fates 30 . ECs express the solute carrier family 1 member 5 (SLC1A5) to take up glutamine and were reported to have high glutaminase (GLS) activity 31, 32 ; this enzyme converts glutamine to glutamate in the first and rate-limiting step of glutaminolysis (the series of reactions that serves to supply glutamine carbons to the tricarboxylic acid (TCA) to replenish intermediates that were used for biosynthesis purposes (anaplerosis)) (Fig. 1).…”