Erythrocytes By-Products of l-Arginine Catabolism

l-Arginine is not only used as a precursor for protein synthesis, but it also functions as building stone for the synthesis of nitric oxide (NO), urea, ornithine, citrulline, creatinine, agmatine, glutamate, proline, and polyamines (Wu and Morris. Biochem J 336(Pt 1):1–17, 1998). Arginine is relatively abundant in the blood in its “free” form, and its blood concentration is mainly affected by food intake, by protein turnover, as well as by arginine supply via the kidney (Wu and Morris. Biochem J 336(Pt 1):1–17, 1998). This dibasic amino acid is conditionally essential during growth and is included in many pharmacological and nutritional formulations (Saitoh et al. J Toxicol Sci 39:41–50, 2014). In the urea cycle, arginine is derived from arginosuccinate and is further metabolized to produce urea and the amino acid ornithine (Wu and Morris. Biochem J 336(Pt 1):1–17, 1998). De novo biosynthesis of arginine uses citrulline as a precursor which, in turn, can be supplied from intestinal glutamine metabolism (Saitoh et al. J Toxicol Sci 39:41–50, 2014). Besides dietary intake, several factors affect the bioavailability of dietary arginine, such as the levels of lysine, manganese, n-3 fatty acids in the diet, and circulating hormones including cortisol, growth hormone, leptin, cytokines, endotoxins, as well as other biomolecules, such as creatine, lactate, ornithine, and methylarginine (Wu et al. Amino Acids 37:153–168, 2009). Here, citrulline is converted to arginine in the body, and pharmacokinetic studies indicate that citrulline is better absorbed and, hence, has a greater systemic bioavailability than arginine (Cynober. J Nutr, 6th Amino acid assessment workshop 1646S–1649S, 2007). Dietary citrulline is also capable of increasing blood levels of arginine and NO without affecting urea output (Virarkar et al. Crit Rev Food Sci Nutr 53(11):1157–1167, 2013).