Abstract
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 alpha-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.
Highlights
In the study with dihydroxyacetone (Study I in Table I), netglucose production was decreased in livers where proline was included in the perfusate, and net glycogen formation was increased
In study 11 (Table I), net glucose uptake with 30 mM glucose as added substrate was increased in livers perfused with a medium containing proline, as was net glycogenesis from glucose
As described in detail under “Experimental Procedures,” proline-containing medium was first perfused through livers of fasted rats for 34 min, and glycogen-rich livers from fed rats were attached glycogen from glucose is unlikely [25]
Summary
We used an isolated liver perfusion system [6] with rats fasted 48 h to study the production of glycogen and glucose with added L-proline and L-glutamine. Hepatic glycogenic rates were calculated based on liver biopsy values under basal conditions, and after 34 and 90 min of perfusion.
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