Control of nitrogen homeostasis: intestinal arginine metabolism regulation according to protein supply.

Abstract

Portal arginine (Arg) flow plays a key role in liver ureagenesis. In the intestine, Arg can be converted into citrulline (Cit) via arginase and ornithine carbamyl-transferase (OCT). Cit can also be synthesized from glutamine via glutaminase and ornithine aminotransferase (OAT). The aim of this work was to study the regulation of these enzymes in the intestine in relation to time and level of protein supply. 48 rats were divided in 6 groups to receive a 10% (10P), 17% (17P) or 25% protein (25P) diet for either 16 hours short-term (ST) or 15 days long-term (LT). LT group urines were collected to determine N balance. At sacrifice, blood was collected for plasma amino acid measurement, and the intestinal mucosa was removed for enzyme expression and activity analysis (results are given as means ± SEM, ANOVA + Newman-Keuls test [∗ vs. 17P: p < 0.05]). N balance remained similar in all groups. Cit plasma levels at LT varied with diet (10P: 87 ± 2 ∗; 17P: 69 ± 4; 25P: 88 ± 5 ∗ in mM). There was an increase in ileum at ST in arginase activity under 25P and 10P diets (respectively 46 ± 2 and 46 ± 2 vs. 36 ± 3 (17P) in μmol/g/min) and at LT, in OAT expression in the 10P group (+ 277 %∗). With an hypoproteic diet, Cit synthesis appears to be ensured by either OAT activation at LT or arginase at ST. Surprisingly, both low and high protein diets increased Cit production. Research is needed to gain further insight into the regulation of this complex metabolic network.