Burton M. Pogell

The two major sites for glyconeogenesis in mammals are liver and kidney (2, 3).Both of these organs contain the specific enzyme, fructose 1,6-diphosphatase, which catalyzes the following reaction (4-6).n-Fructose 1,6-diphosphate Mg++ f n-fructose B-phosphateThis enzymatic step is presumed to be obligatory for glyconeogenesis in order to bypass the highly exergonic phosphofructokinase reaction (7).A sensitive mechanism for the regulation of fructose 1,6-diphosphatase activity would be of importance in control of the direction of flow of carbohydrate metabolism in these organs, i.e. catabolism via glycolysis or glycogenolysis ver.sus the anabolic process of glyconeogenesis.We have recently reported three possible mechanisms for the regulation of liver fructose 1,6-diphosphatase activity under physiological conditions (8): (a) the specific and reversible inhibition by adenosine 5'-monophosphate, (b) the reversible inhibition of the enzyme by substrate at concentrations greater than 0.1 mM, and (c) the reversible inactivation of fructose 1,6diphosphatase by reaction with ATP or ADP.This latter process could be clearly distinguished from inhibition by AMP, since the inactivation did not occur in the presence of either substrate, phosphate, or ethylenediaminetetraacetate and was not reversible by either dilution or overnight dialysis at 4".Our detailed studies on the first two of these mechanisms is the subject of the present report.Recent reports from several other laboratories have confirmed the widespread role of both AMP and fructose 1,6-diphosphate as inhibitors of fructose 1,6-diphosphatase from different sources.Weber (9) first reported inhibition of rat liver fructose 1,6-diphosphatase by excess substrate, and Newsholme (10) and Newsholme and Krebsl have obtained results similar to ours with rat liver extracts.Mendicino and Vasarhely (6) and Salas, Vifiuela, and Sols (11) have shown that both rat kidney and frog

Abstract Palmityl coenzyme A was found to inhibit and inactivate both purified yeast and crude rat liver glucose 6-phosphate dehydrogenase. The yeast enzyme was inhibited 50% at a concentration of 0.0031 mm. The inhibition was strictly competitive and reversible with respect to glucose 6-phosphate and of the mixed type with respect to TPN. Bovine serum albumin and hydroxylamine both prevented and reversed the inhibition, but no restoration of activity was possible once the enzyme became inactivated. Of a group of 12 other enzymes of diverse metabolic function which were tested, 7 were inhibited or inactivated, or both, by very low concentrations of the acyl ester. Glutamic dehydrogenase was found to be the most sensitive as 50% inhibition occurred at 3 x 10-4 mm. In view of the widespread inhibition of enzymes by palmityl coenzyme A and other acyl coenzyme A esters, the physiological role of these esters as regulators of certain metabolic pathways must be viewed with reservation.