Citrulline is an amino acid made from ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from arginine as a by-product of the reaction catalyzed by NOS family (NOS).
Citrulline gets its name from its high concentration in the watermelon Citrullus vulgaris.
In human kidneys, citrulline and aspartic acid are united by argininosuccinate synthetase (ASS) to produce arginosuccinate. The degradation of arginosuccinate to fumarate and arginine is a primary mechanism for sustaining plasma levels of arginine. The same enzyme acts in liver cells to complete the urea cycle. Plasma citrulline has been used as a marker for reduced small intestinal mass, intestinal injury and rejection of small bowel transplants. Plasma citrulline rises in proportion to enterocytes mass, reflecting the unique capacity of enterocytes for net conversion of glutamine into citrulline.
Both classic and type II citrullinemia are associated with known gene alterations. Plasma citrulline elevation is also used as a marker of postoperative intestinal failure. Nitric oxide (NO) synthesis from arginine results in lower production of citrulline. Low availability of NO may be due to inactivation of NO or inhibition of synthesis, which may be detected by lowered production of citrulline.
If aspartic acid, citrulline, and to a lesser extent, arginine are on the low side, these results would be consistent with an elevated rate of consumption of amino acids for fuel. They are all involved in the urea cycle, which converts ammonia to urea. Ammonia is generated when amino acids are burned as fuel.
High plasma or urinary citrulline can indicate a functional enzyme block in the urea cycle, leading to an ammonia buildup. Supplement magnesium and aspartic acid add to drive the cycle. Lower protein intake is suggested in ammonia toxicities.
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