TY - JOUR
T1 - Glyconeogenesis from L-proline involves metabolite inhibition of the glucose-6-phosphatase system
AU - Bode, Ann M.
AU - Foster, James D.
AU - Nordlie, Robert C.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1992/2/15
Y1 - 1992/2/15
N2 - L-Proline's glycogenic action is unlike that of other amino acids in that it produces effects beyond those explainable by a simple increase in osmolarity (Baquet, A., Hue, L., Meijer, A. J., van Woerkom, G. M., and Plomp, P. J. A. M. (1990) J. Biol. Chem. 265, 955-959). We postulate that this effect may relate to inhibition of hepatic glucose-6-P hydrolysis by a proline-derived metabolite. We tested this hypothesis with isolated livers from rats fasted 48 h which were perfused with L-proline or L-glutamine. Net glucose and net glycogen production and levels of glucose-6-P and certain other hepatic metabolites were measured. The data obtained support our hypothesis by demonstrating fundamental differences in the metabolic fates of proline and glutamine in the liver. Both pass through α-ketoglutarate in the initial stage of gluconeogenesis, but proline supports hepatic glycogen formation while glutamine does not. The concomitant increase in hepatic glucose-6-P and proline-associated glyconeogenesis suggests that inhibition of glucose-6-P hydrolysis by a proline-derived metabolite may divert glucose-6-P produced from proline from glucose production and to glycogen synthesis. This conclusion is supported by the effects of perfusions with and without proline (3-mercaptopicolinate present) on (a) glyconeogenesis and glucose formation from dihydroxyacetone, (b) net glucose uptake and glycogen formation with 30 mM glucose as substrate, and (c) glucose production from endogenous glycogen in perfused livers from fed rats.
AB - L-Proline's glycogenic action is unlike that of other amino acids in that it produces effects beyond those explainable by a simple increase in osmolarity (Baquet, A., Hue, L., Meijer, A. J., van Woerkom, G. M., and Plomp, P. J. A. M. (1990) J. Biol. Chem. 265, 955-959). We postulate that this effect may relate to inhibition of hepatic glucose-6-P hydrolysis by a proline-derived metabolite. We tested this hypothesis with isolated livers from rats fasted 48 h which were perfused with L-proline or L-glutamine. Net glucose and net glycogen production and levels of glucose-6-P and certain other hepatic metabolites were measured. The data obtained support our hypothesis by demonstrating fundamental differences in the metabolic fates of proline and glutamine in the liver. Both pass through α-ketoglutarate in the initial stage of gluconeogenesis, but proline supports hepatic glycogen formation while glutamine does not. The concomitant increase in hepatic glucose-6-P and proline-associated glyconeogenesis suggests that inhibition of glucose-6-P hydrolysis by a proline-derived metabolite may divert glucose-6-P produced from proline from glucose production and to glycogen synthesis. This conclusion is supported by the effects of perfusions with and without proline (3-mercaptopicolinate present) on (a) glyconeogenesis and glucose formation from dihydroxyacetone, (b) net glucose uptake and glycogen formation with 30 mM glucose as substrate, and (c) glucose production from endogenous glycogen in perfused livers from fed rats.
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M3 - Article
C2 - 1310675
AN - SCOPUS:0026775120
SN - 0021-9258
VL - 267
SP - 2860
EP - 2863
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -