THE PLASMA FLUX AND OXIDATION RATE OF ORNITHINE ADAPTIVELY DECLINE WITH RESTRICTED ARGININE INTAKE

We hypothesized recently that arginine homeostasis is achieved in huma ns largely by modulating the rate of arginine degradation. We have tes ted this hypothesis further by measuring in vivo the whole body rate o f conversion of arginine to ornithine and ornithine oxidation in six h ealthy young adults. Subjects received for 6 days an L-amino acid-base d diet supplying an arginine-rich or arginine-free intake and on day 7 , following an overnight fast, an 8-h tracer protocol (first 3 h, fast state; next 5 h, fed state) was conducted; L-[guanidino-N-15(2); 5,5- H-2]arginine and L-[5-C-13]ornithine were given as primed, constant in travenous tracers; measurements of the abundances of various isotopolo gs of arginine, ornithine, and citrulline in plasma were made, and fro m these the various kinetic parameters of the metabolism of these amin o acids were derived. Arginine and ornithine fluxes were significantly (P < 0.001) reduced in the fed state with arginine-free feeding. The rates of conversion (mu mol.kg(-1).h(-1); mean +/- SD) of plasma argin ine to ornithine for arginine rich were 12.9 +/- 2.6 and 24.7 +/- 4.8 for fast and fed states. These values were 11.1 +/- 3.5 and 9.6 +/- 1. 2 (P > 0.05 and P < 0.001), respectively, with an arginine-free diet. [C-13]Ornithine oxidation was reduced (P < 0.001) by 46% during the fe d state when the arginine-free diet was given. The findings strengthen our hypothesis that homeostasis of arginine metabolism in the human h ost depends importantly upon a regulation in the rate of arginine degr adation with, perhaps, little involvement in the de novo net rate of a rginine synthesis.