The present study was designed to investigate the metabolism of
glycylglutamine and its effects on organ balances of
amino acids during
intravenous infusion of this
dipeptide (100 mumol.h-1.kg-1) in postabsorptive and briefly starved (84-86 h) human subjects. Arterial concentrations of
glycylglutamine were not significantly different in postabsorptive (265 +/- 18 microM) and starved (241 +/- 13 microM) subjects. Among the organs examined, kidney predominated in clearance of
glycylglutamine from plasma. Moreover, renal clearance of
glycylglutamine was reduced by
starvation (87 +/- 7 vs. 52 +/- 5 mumol/min, P less than 0.01), whereas neither splanchnic nor muscle clearance was significantly affected. Infusion of
glycylglutamine raised plasma concentrations of
glycine and
glutamine by increasing renal release of these
amino acids. In postabsorptive subjects the infusion significantly increased splanchnic balances of
glycine and
glutamine with little or no effect on the muscle balances; the opposite was found in starved subjects. As far as other
amino acids are concerned, the infusion decreased the muscle release of
alanine and increased renal release of
serine. We conclude that the
amino acid residues of
glycylglutamine are largely metabolized by the splanchnic organs in postabsorptive subjects and by peripheral organs in starved subjects. The latter results in selective inhibition of muscle release of
amino acids.