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• W2080589607 abstract "Summary: The amino acid l-arginine (l-Arg) is the substrate for the biosynthesis of nitric oxide (NO) by a variety of cells, including endothelial cells, cytotoxic macrophages, and brain synaptosomes. Although the enzymatic conversion of l-Arg to NO and its cellular regulation is at present the focus of intensive investigations, little is known about the concentration, synthesis, and metabolism of l-Arg by cells capable of producing NO. We have therefore studied the relationship between the metabolism of l-Arg and the biosynthesis of endothelium-derived relaxing factor (EDRF), i.e., NO, in bovine aortic cultured endothelial cells (ECs). The intracellular concentration of l-Arg in cultured ECs was 0.1-0.2 mM, compared with 2-4 mM in freshly isolated ECs from bovine or rabbit aorta. When placed into physiologic buffer solutions, cultured ECs generated l-Arg, and this process was linked to an increase in the release of EDRF. Studies with l-[14C]Arg-labeled ECs showed that the generation of l-Arg was inversely related to a dilution of the l-Arg pool with nonlabeled l-Arg derived from an intracellular source. ECs deficient in l-Arg metabolized l-citrulline (l-Cit) and l-argininosuccinate to l-Arg. Dipeptides containing l-Arg or l-Cit were rapidly cleaved to yield l-Arg orl-Cit, respectively. When superfused with Krebs' solution, ECs maintained their l-Arg level despite the continuous flow-induced release of EDRF. When incubated in Krebs' solution in the presence of the calcium ionophore A 23187, there was only a transient rise in l-Cit, the by-product of EDRF biosynthesis, suggesting a recyclingof l-Cit to l-Arg. The generation of l-Arg was also inversely related to a rapid decrease in intracellular l-glutamine (l-Gln), and both the generation of l-Arg and the release of EDRF were inhibited by l-Gln, a major constituent of the culture medium employed. Cultured ECs did not produce l-ornithine (l-Orn) or urea and d id not metabolize l-Orn to l-Cit. However, they contained and released substantial amounts of ammonia, which was attributable in part to the metabolism of l-Gln. This, instead of a complete urea cycle, cultured ECs possess an l-Arg-l-Cit cycle, which is sensitive to l-Gln and linked to both the biosynthesis of EDRF and the removal of excess nitrogen. It is also possible to imply that the metabolism of l-Arg and hence its availability is an important regulatory factor for the biosynthesis of EDRF." @default.
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• W2080589607 date "1991-01-01" @default.
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• W2080589607 title "The Biosynthesis of Endothelium-Derived Relaxing Factor by Endothelial Cells as a Means of Removing Excess Nitrogen" @default.
• W2080589607 doi "https://doi.org/10.1097/00005344-199117003-00005" @default.
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