Ornithine aminotransferase (OAT) and the response to endotoxemia in mice.

Abstract

OAT catalyzes the only reversible step in the of Arginine (Arg) to Glutamine (Gln) metabolism. Since both these amino acids are strongly involved in the metabolic response to stress, we hypothesized that OAT could act as a limiting enzyme in Gln-Arg interconversion during hypercatabolic stress. The aim of this study was to evaluate the role of OAT using a model of endotoxemia in transgenic mice overexpressing human OAT (liver, kidney, and intestine). Methods Thirty wild-type mice (WT) and 30 transgenic mice (OAT) received an i.p. injection of either lipopolysaccharide (LPS; 10 mg/kg) or NaCl. The animals were sacrificed 5 hours after injection: plasma and tissue (muscle, liver, jejunum) amino acid concentrations and OAT tissue (liver, jejunum) expression and activity. OAT expression and activity in the jejunum and plasma, and tissue Gln and Arg concentrations were similar in all groups. Conclusion Endotoxemia led to a decrease in OAT expression and activity, regardless of whether OAT was overexpressed. OAT overexpression did not affect Gln and Arg homeostasis in endotoxemic mice. Hence, OAT does not appear to be the limiting step in Gln-Arg homeostasis during endotoxemic stress.