Hepatic glutamine metabolism and acid-base regulation.
Switching of hepatic nitrogen disposal from urea synthesis to glutamine production has been proposed as a mechanism for countering acidosis, with glutamine synthesis providing a route for the detoxification of ammonium not incorporated into urea. Isolated livers from starved rats were perfused with ammonium (0.8 mM); increasing perfusate lactate concentration 0-2 mM raised glutamine synthesis threefold whilst increasing perfusate glucose concentration 0-20 mM did not. This was true under normal and acidotic conditions. In the presence of both substrates plus either 14C-glucose or 14C-lactate, the mean specific activity of glutamine synthesised was greater for 14C-lactate. Thus, the preferred substrate for hepatic glutamine synthesis is lactate, a proton neutral reaction. Perfusion with lactate and glutamine over the pH range 6.9-7.5 with or without the glutamine synthase inhibitor L-methionine-s-sulphoxime showed that the switch in acidosis to net glutamine production is entirely due to inhibition of glutamine removal by periportal hepatocytes.
Almond
M K
MK
Medical Unit, London Hospital Medical College, UK.
Iles
R A
RA
Cohen
R D
RD
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D002244:Carbon / Q000737:chemistry*; D005973:Glutamine / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D005973:Glutamine; D002244:Carbon