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===Biosynthesis=== Arginine is synthesized from [[citrulline]] in the urea cycle by the sequential action of the cytosolic enzymes [[argininosuccinate synthetase]] and [[argininosuccinate lyase]]. This is an energetically costly process, because for each molecule of [[Argininosuccinic acid|argininosuccinate]] that is synthesized, one molecule of [[adenosine triphosphate]] (ATP) is hydrolyzed to [[adenosine monophosphate]] (AMP), consuming two ATP equivalents.{{cn|date=July 2024}} The pathways linking arginine, [[glutamine]], and [[proline]] are bidirectional. Thus, the net use or production of these amino acids is highly dependent on cell type and developmental stage.{{cn|date=July 2024}} [[File:Arginine biosynthesis pathway.png|thumb|Arginine biosynthesis|center|500px]] Arginine is made by the body as follows. The [[epithelial cell]]s of the [[small intestine]] produce citrulline, primarily from [[glutamine]] and [[glutamate]], which is secreted into the bloodstream which carries it to the [[proximal tubule cell]]s of the [[kidney]], which extract the citrulline and convert it to arginine, which is returned to the blood. This means that impaired small bowel or renal function can reduce arginine synthesis and thus create a dietary requirement for arginine. For such a person, arginine would become "essential". Synthesis of arginine from citrulline also occurs at a low level in many other cells, and cellular capacity for arginine synthesis can be markedly increased under circumstances that increase the production of [[Nitric oxide synthase#iNOS|inducible nitric oxide synthase (NOS)]]. This allows citrulline, a byproduct of the NOS-catalyzed production of nitric oxide, to be recycled to arginine in a pathway known as the citrulline to nitric oxide (citrulline-NO) or arginine-citrulline pathway. This is demonstrated by the fact that, in many cell types, nitric oxide synthesis can be supported to some extent by citrulline, and not just by arginine. This recycling is not quantitative, however, because citrulline accumulates in nitric oxide producing cells along with [[nitrate]] and [[nitrite]], the stable end-products of nitric oxide breakdown.<ref>{{cite journal | vauthors = Morris SM | title = Enzymes of arginine metabolism | journal = The Journal of Nutrition | volume = 134 | issue = 10 Suppl | pages = 2743Sβ2747S; discussion 2765Sβ2767S | date = October 2004 | pmid = 15465778 | doi = 10.1093/jn/134.10.2743S | department = (review) | doi-access = free }}</ref>
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