Skip to main content
ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #344165

Title: Ablation of arginase II spares arginine and abolishes the arginine requirement for growth in male mice

item DIDELIJA, INKA - Children'S Nutrition Research Center (CNRC)
item MOHAMMAD, MAHMOUD - Children'S Nutrition Research Center (CNRC)
item MARINI, JUAN - Children'S Nutrition Research Center (CNRC)

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/12/2017
Publication Date: 7/5/2017
Citation: Didelija, I.C., Mohammad, M.A., Marini, J.C. 2017. Ablation of arginase II spares arginine and abolishes the arginine requirement for growth in male mice. Journal of Nutrition. 147(8):1510-1516.

Interpretive Summary: Arginine is a semi-essential amino acid that is required in the diet when its demand (e.g., growth, pregnancy) exceeds endogenous production. Arginine is utilized not only for protein synthesis, but also to produce many important compounds such as creatine, nitric oxide, polyamines and other amino acids. The requirement for arginine can be met by increasing the supply of arginine by the diet or by decreasing arginine utilization by certain pathways. One of the main routes of arginine utilization is catabolism by arginase. Wild type male mice fed an arginine free diet grow slower than when they are fed a conventional diet. Here, we studied growing arginase II knockout male mice fed an arginine free diet. These mice grew at the same rate than the wild type mice fed the control diet and faster than the wild type mice fed the arginine free diet. We have showed that manipulating a catabolic pathway of arginine, spares and increases the availability of this amino acid. This may be useful in certain diseases in which arginase activity is increased (trauma, sepsis, sickle cell anemia), because in these conditions increasing arginine supply may not be enough to restore arginine availability.

Technical Abstract: Arginine is considered a semi-essential amino acid in many species, including humans, because under certain conditions its demand exceeds endogenous production. Arginine availability, however, is not only determined by its production, but also by its disposal. Manipulation of disposal pathways has the potential to increase availability and thus abolish the requirement for arginine. The objective of the study was to test the hypothesis that arginase II ablation increases arginine availability for growth. In a completely randomized design with a factorial arrangement of treatments post-weaning growth was determined for three weeks in male and female wild type (WT) and arginase II ko (ARGII) mice on a C57BL/6J background fed arginine sufficient (8 g/kg diet) or arginine-free diets Tracers were used to determine citrulline and arginine kinetics. A sex dimorphism in arginine metabolism was detected; female mice had a greater citrulline flux (~30%; P < 0.001), which translated in greater de novo synthesis of arginine (~31%, P<0.001). Female mice also had greater arginine flux (P<0.015), plasma arginine concentration (P <0.01), but a reduced arginine clearance rate (P<0.001). Ablation of arginase II increased plasma arginine concentrations in both sexes (~27%, P<0.01), but increased arginine flux only in males (P<0.01). The absence of arginine in the diet limited the growth of male WT mice (P<0.01), but had no effect on male ARGII mice (P = 0.12). In contrast, WT females on the arginine free diet grew at the same rate and achieved similar final weight to female WT mice fed the arginine sufficient diet (P = 0.47). The ablation of arginase II in male mice spares arginine that can then be utilized for growth and to meet other metabolic functions thus abolishing arginine requirements.