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Pathway: citrulline biosynthesis

General Background |FRAME: L-CITRULLINE| is a non-standard amino acid that is not normally incorporated into proteins during protein synthesis. The name citrulline was coined in 1930 from Citrullus, the Latin name of the watermelon, from which it was first isolated. Free citrulline is formed mainly by catabolism of amino acids in the small intestine (see |FRAME:CITRULBIO-PWY|), as an intermediate in the conversion of ammonia to urea in the |FRAME:PWY-4984|, and as a by-product during the production of nitric oxide (see |FRAME:PWY-4983|). In addition, citrulline is also formed by modification of arginine residues in proteins (see |FRAME: PWY-4921|). About This Pathway Most of the citrulline circulating in the blood of mammals comes from glutamine conversion in enterocytes, the intestinal absorptive cells found in the mucosa of the small intestine. Several other amino acids can also act as citrulline precursors, including glutamate, proline, and arginine. In rats, 28% of these metabolized amino acids are converted into citrulline. Two glutamate molecules are required for the synthesis of each citrulline molecule, only one of which can be substituted by another amino acid. The citrulline that is formed in the intestinal mucosa enters the blood stream, and reaches the kidneys, where it is coverted into arginine (see |FRAME:PWY-5004|). In adults, this citrulline to arginine conversion provides the body's full arginine requirements |CITS:[16082501]|. About 83% of the citrulline released from the intestine is metabolized by the kidneys |CITS:[7325229]|, and the rest is used for nitric acid production within other tissues. In new born mammals, which have a much larger need for arginine, proline is the main source of citrulline synthesis in the gut |CITS:[10329997]|. In addition, in new borns conversion of citrulline to arginine is not limited to the kidneys, and occurs in the intestinal mucosa as well. Inhibition of intestinal citrulline synthesis causes severe growth retardation |CITS:[4083357]|.


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