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Urea synthesis in enterocytes of developing pigs.

ABSTRACT: Urea synthesis from ammonia, glutamine and arginine was determined in enterocytes from newborn (0-day-old), 2-21-day-old suckling, and 29-58-day-old post-weaning pigs. Pigs were weaned at 21 days of age. Cells were incubated for 30 min at 37 degrees C in Krebs-Henseleit bicarbonate buffer (pH 7.4) containing (i) 0.5-2 mM NH4Cl plus 0.05-2 mM ornithine and 2 mM aspartate, (ii) 1-5 mM glutamine, or (iii) 0.5-2 mM arginine. In enterocytes from newborn and suckling pigs, there was no measurable synthesis of urea from ammonia, glutamine or arginine, and analysis of amino acids by a sensitive fluorimetric HPLC method revealed the formation of negligible amounts of ornithine from arginine. In contrast, in cells from post-weaning pigs, relatively large amounts of urea and ornithine were produced from ammonia, glutamine and arginine in a dose-dependent manner. To elucidate the mechanism of the developmental change of urea synthesis in pig enterocytes, the activities of urea-cycle enzymes were determined. The activities of enterocyte carbamoyl phosphate synthase I and ornithine carbamoyltransferase were lower in post-weaning pigs than in suckling ones, whereas there was no difference in arginino-succinate lyase. The activities of argininosuccinate synthase and arginase were increased by 4-fold and 50-100-fold, respectively, in enterocytes from post-weaning pigs compared with suckling pigs. The induction of arginase appears to be sufficient to account for the formation of urea from ammonia, glutamine and arginine in post-weaning pig enterocytes. These results demonstrate for the first time the presence of synthesis of urea from extracellular or intramitochondrially generated ammonia in enterocytes of post-weaning pigs. This hitherto unrecognized urea synthesis in these cells may be a first line of defence against the potential toxicity of ammonia produced by the extensive intestinal degradation of glutamine (a major fuel for enterocytes) and derived from diet and luminal micro-organisms.

SUBMITTER: Wu G

PROVIDER: S-EPMC1136173 | biostudies-other | 1995 Dec

REPOSITORIES: biostudies-other

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Project description:Background and aimData on quantitative metabolic liver functions in the life-threatening disease alcoholic hepatitis are scarce. Urea synthesis is an essential metabolic liver function that plays a key regulatory role in nitrogen homeostasis. The urea synthesis capacity decreases in patients with compromised liver function, whereas it increases in patients with inflammation. Alcoholic hepatitis involves both mechanisms, but how these opposite effects are balanced remains unclear. Our aim was to investigate how alcoholic hepatitis affects the capacity for urea synthesis. We related these findings to another measure of metabolic liver function, the galactose elimination capacity (GEC), as well as to clinical disease severity.MethodsWe included 20 patients with alcoholic hepatitis and 7 healthy controls. The urea synthesis capacity was quantified by the functional hepatic nitrogen clearance (FHNC), i.e., the slope of the linear relationship between the blood α-amino nitrogen concentration and urea nitrogen synthesis rate during alanine infusion. The GEC was determined using blood concentration decay curves after intravenous bolus injection of galactose. Clinical disease severity was assessed by the Glasgow Alcoholic Hepatitis Score and Model for End-Stage Liver Disease (MELD) score.ResultsThe FHNC was markedly decreased in the alcoholic hepatitis patients compared with the healthy controls (7.2±4.9 L/h vs. 37.4±6.8 L/h, P<0.01), and the largest decrease was observed in those with severe alcoholic hepatitis (4.9±3.6 L/h vs. 9.9±4.9 L/h, P<0.05). The GEC was less markedly reduced than the FHNC. A negative correlation was detected between the FHNC and MELD score (rho = -0.49, P<0.05).ConclusionsAlcoholic hepatitis markedly decreases the urea synthesis capacity. This decrease is associated with an increase in clinical disease severity. Thus, the metabolic failure in alcoholic hepatitis prevails such that the liver cannot adequately perform the metabolic up-regulation observed in other stressful states, including extrahepatic inflammation, which may contribute to the patients' poor prognosis.

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Urea synthesis in enterocytes of developing pigs.

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