Abstract
The effects of free fatty acids on rat liver phosphoenolpyruvate carboxykinase (EC 4.1.1.32), pyruvate carboxylase (EC 6.4.1.1), and glucose 6-phosphatase (EC 3.1.3.9) were determined to evaluate the suggestion that free fatty acid inhibition of key glycolytic enzymes constitutes a specific inhibitory effect. Activities of all of these gluconeogenic enzymes were found to be markedly inhibited by long chain free fatty acids as well as by palmitoyl coenzyme A. The manner of the inhibition of gluconeogenic enzymes was indistinguishable from that reported for the glycolytic enzymes. It is therefore concluded that such effects in vitro of free fatty acids or long chain acyl-CoA esters on glycolytic and gluconeogenic enzymes may not be relevent for the regulation of metabolism in vivo.
Highlights
Evaluate the suggestion that inhibition of key glycolytic enzymes by free fatty acids could regulate gluconeogenesisby suppressing glycolysis, we have investigated the specificity of free fatty acid inhibition by determining the effects of free fatty acids on key gluconeogenic enzymes
It was to be expected that these enzymes would not be subject to inhibition by free fatty acids if the contention [6,7,8,9, 11] that free fatty acids selectively inhibited key glycolytic enzymes without affecting gluconeogenic enzymes were to be valid
Similar to the free fatty acid inhibition of glycolytic enzymes, which is increased by increasing the time of preliminary incubation of enzymes with free fatty acids [6, 7], the inhibition of pyruvate carboxylase by oleate was a timedependent effect
Summary
LMuteriuZs--Phosphoenolpyruvate, NADH, pyruvic acid (potassium salt), ATP, palmitoyl-CoA, oxalacetic acid, ADP, dithiothreitol, lactate dehydrogenase, Tris (Sigma-121), malate dehydrogenase, bovine serum albumin, and glucose g-phosphate were obtained from Sigma Chemical Company. Acetyl-CoA and ITP were P-L Biochemical products. Pyruvate kinase was obtained from Boehringer (Germany), NaH14C08 from New. England Nuclear Corporation, and oleate from Serdary Research Laboratories (Canada). ( -)-Palmitoylcarnitine was a gift from Dr S. Enzyme Prepurutions-Supernatant and microsomes from rat liver were prepared as described before [12] and kept frozen when not in use. The supernatant and the microsomal fractions were used, respectively, as sources of phosphoenolpyruvate carboxykinase and glucose 6phosphatase. Mitochondrial fraction from rat liver was prepared as described by Johnson and Lardy [13]
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