RECIPROCAL EFFECTS OF PROLINE AND GLUTAMINE ON GLYCOGENESIS FROM GLUCOSE AND UREAGENESIS IN ISOLATED, PERFUSED RAT LIVERS

L-Proline and L-glutamine were used to probe the inverse relationship between glycogenesis and ureagenesis in isolated, perfused livers from 48-h fasted rats. Both amino acids may provide nitrogen in the form o f NH4+ for carbamyl-P synthesis. However, one molecule of glutamine ma y provide additionally for the synthesis of one molecule of the urea c ycle substrate L-aspartate, but proline can provide for the synthesis of a molecule of NH4+ or one molecule of aspartate on an either/or bas is only. In all perfusates, glucose was initially 30 mM (to favor phos photransferase activity of glucose-6-phosphatase) and 0.5 mM 3-mercapt opicolinate was present (to inhibit glyconeogenesis from endogenous su bstrates, from the added amino acids, and via the indirect pathway). G lycogenesis from glucose, perfusate and hepatic urea formation, and le vels of hepatic glucose-6-P, citrulline, PP(i), and carbamyl-P were me asured. The addition of glutamine to the perfusate markedly stimulated the urea cycle, but not glycogenesis. Hepatic urea level, perfusate u rea concentration, and hepatic citrulline and PP(i) increased while ca rbamyl-P content decreased. In contrast, proline stimulated glycogenes is from glucose, but not ureagenesis. In the proline-supplemented comp ared with glutamine group, hepatic glycogenesis and carbamyl-P content increased; hepatic glucose-6-P levels showed a tendency toward increa se; and hepatic urea formation, hepatic citrulline, and PP(i) levels w ere decreased. These observations are interpreted to support an hepati c mechanism whereby the relative availability of carbamyl-P to the ure a cycle and as a substrate for glucose phosphorylation via phosphotran sferase activity of the glucose-6-phosphatase system preliminary to gl ycogenesis from glucose is a major metabolic determinant.