Quantitative aspects of interorgan relationships among arginine and citrulline metabolism

The quantitative roles of the splanchnic region and the kidneys in whole body (WB) arginine and citrulline metabolism were assessed in postabsorptive mongrel dogs with primed constant intravenous infusions of [15N2-guanidino, 5,5-2H2]arginine and [13C-ureido]citrulline or [13C-guanidino]arginine and [15N]urea tracers. Isotope and metabolite concentration balances of arginine and citrulline were measured across the gut, liver, splanchnic region, and kidneys, together with WB arginine and citrulline fluxes and urea production rate. The WB citrulline flux and rate of citrulline to arginine (C-A) conversion were 16 and 9.4 mumol.kg-1.h-1, respectively. Concentration balance of citrulline across kidneys was +8.2 mumol.kg-1.h-1, and metabolism of citrulline by kidneys was 8.7 mumol.kg-1.h-1, which was derived about equally from intestine and liver. The appearance rate of citrulline-derived arginine in renal vein was 6.8 mumol.kg-1.h-1. These three separate estimates of C-A conversion within the kidneys were in good agreement, indicating 40% of blood C-A conversion occurring outside kidneys. These findings of interorgan metabolism are discussed in reference to the current knowledge derived largely from studies in laboratory rodents.