Citrulline: A New Player in the Control of Nitrogen Homeostasis

Abstract

Citrulline (CIT) is an amino acid that is not involved in protein synthesis but that is tightly linked to arginine (ARG) metabolism. CIT displays a very specific metabolism: In the 1980s, Windmuller demonstrated that the small intestine releases CIT, which is mainly taken up by the kidney and metabolized into ARG. Because CIT is not taken up by the liver, this ARG-CIT-ARG cycle can be seen as a means of protecting dietary ARG from liver degradation and of sustaining protein homeostasis. These observations have led to the concept that plasma CIT concentration would be a good marker of intestinal failure in short bowel syndrome. Hence, in massive intestinal resection, citrullinemia is greatly reduced, and this is proportional to the severity of the intestinal disease. This concept was then extended to other situations in which the intestinal function is compromised. The data strongly suggest that CIT may be a conditionally essential amino acid in situations where the intestinal function is compromised. Recent data support this idea. Thus, CIT supplementation is able to restore nitrogen balance, generate large amounts of ARG in rats with short bowel syndrome, and increase muscle protein content (+20%) as well as muscle protein synthesis (+90%) in elderly malnourished rats. Finally, recent data indicate that CIT per se could be able to stimulate muscle protein synthesis. Hence, CIT could play a pivotal role in maintaining protein homeostasis, and the determination of the underlying mechanisms involved in its action should be important for the development of new nutritional strategies in malnourished patients with compromised intestinal functions.

A 4-week oral gavage toxicity study of L-citrulline in rats

“…As a key regulator of endogenous L-citrulline production, the small intestine plays an important role in L-citrulline supply to the body (Moinard and Cynober, 2007). In addition, orally supplemented L-citrulline is converted to L-argininosuccinate by argininosuccinate synthase and subsequently to L-arginine by argininosuccinate lyase, mainly in the kidney (Moinard et al, 2008;Romero et al, 2006).…”

“…It was also suggested that L-citrulline could play a pivotal role in the control of nitrogen homeostasis (Moinard and Cynober, 2007). Thus, L-citrulline is widely used as a food supplement for vascular function and exercise performance in sport nutrition in Japan and USA.…”

Enhanced L-citrulline in parboiled paddy rice with watermelon (Citrullus lanatus) juice for preventing Sarcopenia: A preliminary study

“…L-citrulline increases the blood concentration of L-arginine more effectively than oral L-arginine, as L-citrulline undergoes neither intestinal nor hepatic metabolism, is not a substrate for arginase, and does not induce the expression or activity of the enzyme (Orozco-Gutiérrez et al, 2010). Using L-citrulline to combat sarcopenia has been assessed in clinical trials with promising results (Bahri et al, 2013;Moinard and Cynober, 2007) and plays a key role in the immune system (Yu et al, 1995).…”

Improvement of ventricular function in systolic heart failure patients with oral L-citrulline supplementation

“…Glutamine supplements have been studied, but only 27% is converted into citrulline [10]. Van de Poll et al [5] demonstrated that the generation of citrulline through glutamine represented only 13% of the intestinal metabolism [5][6][7][8][9].…”

“…Van de Poll et al [5] demonstrated that the generation of citrulline through glutamine represented only 13% of the intestinal metabolism [5][6][7][8][9]. The characteristic of citrulline is that it is absorbed completely without any hepatic consumption [10], suggesting that it could be a better supplementation choice [6,10].…”