RAPID ACTIVATION OF HEPATIC GLUTAMINASE IN RATS FED ON A SINGLE HIGH-PROTEIN MEAL

We report that hepatic glutaminase is rapidly activated in rats fed on a single high-protein (60 % casein) meal. Rats previously fed on a no rmal-protein (15% casein) diet for 3-4 days were given a high-protein meal for 2 h. The high-protein meal increased the rate of flux through glutaminase in intact liver mitochondria nearly 3-fold (20.6 +/- 1.7 nmol/min per mg of protein versus 7.5 +/- 2.9 nmol/min per mg of prote in) at a P(i) concentration of 10 mM. The activation of flux through g lutaminase by a high-protein meal involved an increased sensitivity of glutaminase to P(i), an activator of the enzyme. The K(a) for P(i) wa s 1.0 mM and 24.1 mM in mitochondria from rats fed on the high-protein and normal-protein meals respectively. We measured the concentration of P(i) in the mitochondrial matrix and found that it did not differ i n mitochondria from rats fed on the high-protein and normal-protein me als, suggesting that the effect of the high-protein meal on the P(i)-s ensitivity of glutaminase was not due to a change in the distribution of P(i) across the mitochondrial inner membrane. Glutaminase activity was measured by using mitochondrial membranes from frozen-thawed mitoc hondria. Glutaminase activity and its dependence on P(i) were similar for preparations from rats fed on high-protein and normal-protein meal s. These findings show that hepatic glutaminase is stimulated rapidly by a high-protein meal. This is part of the physiological hepatic resp onse to increased protein intake which permits the liver to cope with the influx of glutamine occurring at this time.