Control of hepatic utilization of glutamine by transport processes or cellular metabolism in rats fed a high protein diet.

The hepatic metabolism of glutamine in rats adapted to a 15% casein high carbohydrate (HC) diet was compared to that in rats adapted to a 70% casein high protein (HP) diet. Portal glutamine concentrations in rats fed the HP diet were twice as high as those in rats fed the HC diet and glutamine was very efficiently extracted (40%) by the liver of rats fed the HP diet. From experiments of intraportal infusion of glutamine, it appeared that higher capacities of glutamine uptake develop in vivo in rats adapted to an HP diet. Hepatocytes isolated from such animals displayed higher capacities to metabolize glutamine to urea, even at physiological concentrations. This resulted from an increase of mitochondrial glutamine hydrolysis (observed in both intact and disrupted mitochondria) and from enhanced Na+-dependent glutamine transport (+50%, as measured by plasma membrane vesicles). In hepatocytes from rats fed the HC diet, glutamine breakdown was more efficiently stimulated by glucagon (and cAMP) than by vasopressin or epinephrine. In hepatocytes from rats fed the HP diet, this process was very responsive to both cAMP and Ca-dependent hormones. Metabolic adaptation to an HP diet results in the liver becoming a major site of glutamine utilization caused by adaptations of membrane transport, cell metabolism and tissue responsiveness to hormones.