title: Dietary arginine requirements for growth are dependent on the rate of citrulline production in mice.
abstract: BACKGROUND
  In many species, including humans, arginine is considered a semiessential amino acid because under certain conditions endogenous synthesis cannot meet its demand. The requirements of arginine for growth in mice are ill defined and seem to vary depending on the genetic background of the mice.
  
  
  OBJECTIVE
  The objective of this study was to determine the metabolic and molecular basis for the requirement of arginine in 2 mouse strains.
  
  
  METHODS
  Institute of Cancer Research (ICR) and C57BL/6 (BL6) male mice were fed arginine-free or arginine-sufficient diets (Expt. 1) or 1 of 7 diets with increasing arginine concentration (from 0- to 8-g/kg diet, Expt. 2) between day 24 and 42 of life to determine the arginine requirements for growth. Citrulline production and "de novo" arginine synthesis were measured with use of stable isotopes, and arginine requirements were determined by breakpoint analysis and enzyme expression by reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  In Expt. 1, ICR mice grew at the same rate regardless of the arginine concentration of the diet (mean ± SE: 0.66 ± 0.04 g/d, P = 0.80), but BL6 mice had a reduced growth rate when fed the arginine-free diet (0.25 ± 0.02 g/d, P < 0.001) compared to the 8-g arginine/kg diet (0.46 ± 0.03 g/d). ICR mice showed at least a 2-fold greater expression (P < 0.001) of ornithine transcarbamylase (OTC) than BL6 mice, which translated into a greater rate of citrulline (25%) and arginine synthesis (49%, P < 0.002). In Expt. 2, breakpoint analysis showed that the requirement for growth of BL6 mice was met with 2.32 ± 0.39 g arginine/kg diet; for ICR mice, however, no breakpoint was found.
  
  
  CONCLUSIONS
  Our data indicate that a reduced expression of OTC in BL6 mice translates into a reduced production of citrulline and arginine compared with ICR mice, which results in a dietary arginine requirement for growth in BL6 mice, but not in ICR mice.
authors: Pediatric Critical Care Medicine and USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX marini@bcm.edu.
authors: Juan C
authors: JC
authors: Marini
authors: USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors: Umang
authors: U
authors: Agarwal
authors: USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors: Inka C
authors: IC
authors: Didelija
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage* / Q000096:biosynthesis; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000235:genetics / Q000378:metabolism; D002956:Citrulline / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009751:Nutritional Requirements; D009954:Ornithine Carbamoyltransferase / Q000235:genetics / Q000378:metabolism; D014886:Weaning
chemical_list: D002956:Citrulline; D001120:Arginine; D009954:Ornithine Carbamoyltransferase; D002222:Carbamoyl-Phosphate Synthase (Ammonia)
keywords: amino acid; arginine; citrulline; growth; requirements