Effect of glutamine on glutathione kinetics in vivo in dogs.
To determine whether glutamine affects glutathione (GSH, gamma-glutamyl-cysteinyl-glycine) metabolism, seven healthy beagle dogs received 6-h infusions of [(15)N]glutamate and [(13)C]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 [(15)N]glutamate incorporation into blood and gut GSH, and duodenal protein synthesis from [(13)C]leucine incorporation into gut protein. Glutamine supplementation failed to alter erythrocyte GSH concentration (2189+/-86 vs. 1994+/-102 micromol 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 micromol 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.
INSERM U.539, Centre de Recherche en Nutrition Humaine, Nantes, 44093 Cedex 1, France.
Bernard
B
Humbert
Patrick
P
Nguyen
Lucile
L
Martin
Henri
H
Dumon
Geneviève
G
Vallette
Pascale
P
Maugère
Dominique
D
Darmaun
D000818:Animals; D004285:Dogs; D004386:Duodenum / Q000378:metabolism; D004750:Enteral Nutrition; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D018698:Glutamic Acid / Q000097:blood; D005973:Glutamine / Q000097:blood / Q000494:pharmacology*; D005978:Glutathione / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D008297:Male; D023421:Models, Animal; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis
D005973:Glutamine; D018698:Glutamic Acid; D005978:Glutathione