The Metabolism of L-Arginine and Its Significance for the Biosynthesis of Endothelium-Derived Relaxing Factor: L-Glutamine Inhibits the Generation of L-Arginine by Cultured Endothelial Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 21; pp. 8607 - 8611
• Main Authors: Sessa, William C., Hecker, Markus, Mitchell, Jane A., Vane, John R.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-11-1990; National Acad Sciences
• Subjects: 550201 - Biochemistry- Tracer Techniques; AMINO ACIDS; Ammonia; ANIMAL CELLS; ANIMAL TISSUES; Animals; AORTA; Aorta - drug effects; Aorta - physiology; ARGININE; Arginine - metabolism; Argininosuccinic Acid - metabolism; ARTERIES; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; BIOSYNTHESIS; BLOOD VESSELS; BODY; CARBON 14 COMPOUNDS; CARBON COMPOUNDS; CARBOXYLIC ACIDS; CARDIOVASCULAR AGENTS; CARDIOVASCULAR SYSTEM; Cattle; CELL CULTURES; Cell Line; Cell lines; Cell physiology; Cells, Cultured; Cellular metabolism; CHROMATOGRAPHY; Citrulline - metabolism; CONNECTIVE TISSUE CELLS; Cultured cells; DRUGS; Endothelial cells; ENDOTHELIUM; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; endothelium-derived relaxing factor; Fundamental and applied biological sciences. Psychology; Glutamates - pharmacology; Glutamic Acid; Glutamine - pharmacology; Hepatocytes; In Vitro Techniques; LABELLED COMPOUNDS; MACROPHAGES; METABOLISM; Mice; Microelectromechanical systems; Molecular and cellular biology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Nitric Oxide - biosynthesis; Nitric Oxide - metabolism; Nitric Oxide - pharmacology; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PHAGOCYTES; Rabbits; Responses to growth factors, tumor promotors, other factors; SEPARATION PROCESSES; SOMATIC CELLS; SYNTHESIS; THIN-LAYER CHROMATOGRAPHY; TISSUES; VASODILATORS; Culture medium; Endothelial cell; Bovine; Biosynthesis; Vertebrata; Mammalia; Arginine; Aorta; Artiodactyla; Endothelium derived relaxing factor; Inhibition; Ungulata; Release; Glutamine
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.21.8607

The mechanism by which L-glutamine (L-Gln) inhibits the release of endothelium-derived relaxing factor from bovine aortic cultured endothelial cells was investigated. The intracellular concentration of L-arginine (L-Arg) in Arg-depleted endothelial cells was inversely related to the level of L-Gln. Removal of L-Gln from the culture medium (usually containing L-Gln at 2 mM) abolished the inhibitory effect of the culture medium on L-Arg generation. L-Gln (0.2 and 2 mM) but not D-Gln inhibited the generation of L-Arg by both Arg-depleted and nondepleted endothelial cells. L-Gln did not interfere with the uptake of L-Arg or the metabolism of L-Arg-L-Phe to L-Arg but inhibited the formation of L-Arg from L-Citrulline (L-Cit), L-Cit-L-Phe, and NG-monomethyl-L-arginine. L-Gln also inhibited the conversion of L-[14C]Cit to L-[14C]Arg by Arg-depleted endothelial cells. However, L-Gln did not inhibit the conversion of L-argininosuccinic acid to L-Arg by endothelial cell homogenates. Thus, L-Gln interferes with the conversion of L-Cit to L-Arg probably by acting on argininosuccinate synthetase rather than argininosuccinate lyase. L-Gln also inhibited the generation of L-Arg by the monocyte-macrophage cell line J774 but had no effect on the conversion of L-Cit to L-Arg by these cells. As the release of endothelium-derived relaxing factor from cultured and noncultured endothelial cells is limited by the availability of L-Arg, endogenous L-Gln may play a regulatory role in the biosynthesis of endothelium-derived relaxing factor.