The effect of 4 days methionine sulfoximine administration on net muscle protein breakdown in rats

It has been suggested that the amino acid glutamine is essential for the regulation of protein turnover in muscle, but in vivo data are lacking. Therefore, administration of methionine sulfoximine (MSO) was used to inhibit glutamine synthetase activity and to induce in vivo muscle glutamine depletion. Glutamine metabolism of the hindquarter was measured by determining fluxes and intracellular concentrations after an overnight fast in ether anaesthetized normal rats, MSO treated rats and their pairfed controls. Fluxes and intracellular concentrations of several other amino-acids including 3-methylhistidine and ammonia were also determined. MSO treatment resulted in a 50% decrease in arterial glutamine concentration, a 55% reduction in intracellular muscle glutamine and a 50% increase in muscle ammonia. Four day MSO treatment significantly increased hindquarter muscle plasma flow. Precursors of muscle glutamine synthesis seem to be preferentially used for increased production of alanine. Ammonia was found to be released in increased amounts. The increased efflux of amino-acids including phenylalanine and tyrosine indicate that MSO treatment induces net muscle protein catabolism. These results suggest that, in vivo, reduced intramuscular glutamine concentrations correlate with increased net muscle protein breakdown.