Effect of glutamine on glutathione kinetics in vivo in dogs

To determine whether glutamine affects glutathione (GSH, γ-glutamyl-cysteinyl-glycine) metabolism, seven healthy beagle dogs received 6-h infusions of [15N]glutamate and [13C]leucine after a 3-day fast. Isotope infusions were performed during oral feeding with an elemental regimen, supplemented with either l-glutamine or an isonitrogenous amino acid mixture, on two separate days and in randomized order. Timed blood samples were obtained, and a surgical duodenal biopsy was performed after 6 h of isotope infusion. GSH fractional synthesis rate (FSR) was assessed from [15N]glutamate incorporation into blood and gut GSH, and duodenal protein synthesis from [13C]leucine incorporation into gut protein. Glutamine supplementation failed to alter erythrocyte GSH concentration (2189±86 vs. 1994±102 μmol L−1 for glutamine vs. control; ns) or FSR (64±17% vs. 74±20% day−1; ns). In the duodenum, glutamine supplementation was associated with a 92% rise in reduced/oxidized GSH ratio (P=.024) and with a 44% decline in GSH FSR (96±15% day−1 vs. 170±18% day−1; P=.005), whereas total GSH concentration remained unchanged (808±154 vs. 740±127 μmol kg−1; P=.779). We conclude that, in dogs receiving enteral nutrition after a 3-day fast: (1) glutamine availability does not affect blood GSH, and, (2) in contrast, in the duodenum, the preserved GSH pool, along with a decreased synthesis rate, suggests that glutamine may maintain GSH pool and intestinal redox status by acutely decreasing GSH utilization.