Phosphoenolpyruvate Cycling via Mitochondrial Phosphoenolpyruvate Carboxykinase Links Anaplerosis and Mitochondrial GTP with Insulin Secretion

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Phosphoenolpyruvate Cycling via Mitochondrial Phosphoenolpyruvate Carboxykinase Links Anaplerosis and Mitochondrial GTP with Insulin Secretion*

Pancreatic beta-cells couple the oxidation of glucose to the secretion of insulin. Apart from the canonical K(ATP)-dependent glucose-stimulated insulin secretion (GSIS), there are important K(ATP)-independent mechanisms involving both anaplerosis and mitochondrial GTP (mtGTP). How mtGTP that is trapped within the mitochondrial matrix regulates the cytosolic calcium increases that drive GSIS rem...

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Kinetic and functional properties of human mitochondrial phosphoenolpyruvate carboxykinase

The cytosolic form of phosphoenolpyruvate carboxykinase (PCK1) plays a regulatory role in gluconeogenesis and glyceroneogenesis. The role of the mitochondrial isoform (PCK2) remains unclear. We report the partial purification and kinetic and functional characterization of human PCK2. Kinetic properties of the enzyme are very similar to those of the cytosolic enzyme. PCK2 has an absolute require...

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Mitochondrial phosphoenolpyruvate carboxykinase (GTP) and the regulation of gluconeogenesis and ketogenesis in avian liver.

Chicken liver synthesizes glucose from lactate and dihydroxyacetone at high rates but pyruvate, glycerol, alanine, and other amino acids are poor glucose precursors. Despite its limited conversion to glucose, 1 m~ pyruvate completely suppressed ketone body synthesis from octanoate by perfused chicken liver, whereas lactate at this concentration had no effect on ketogenesis. Also, increasing the...

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The mitochondrial and cytosolic forms of avian phosphoenolpyruvate carboxykinase (GTP) are encoded by different messenger RNAs.

Previous work from our laboratory (Watford, M., Hod, Y., Chiao, Y. B., Utter M. F., and Hanson R. W. (1981) J. Biol. Chem. 256, 10023-10027) indicated that in the chicken, hepatic phosphoenolpyruvate carboxykinase is in the mitochondria, whereas kidney contains both a mitochondrial and cytosolic form of the enzyme. In the present study the two forms of phosphoenolpyruvate carboxykinase were pur...

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Inactivation of chicken mitochondrial phosphoenolpyruvate carboxykinase by o-phthalaldehyde.

Chicken liver mitochondrial phosphoenolpyruvate carboxykinase is inactivated by o-phthalaldehyde. The inactivation followed pseudo first-order kinetics, and the second-order rate constant for the inactivation process was 29 M-1 s-1 at pH 7.5 and 25 degrees C. The modified enzyme showed maximal fluorescence at 427 nm upon excitation at 337 nm, consistent with the formation of isoindole derivativ...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2009

ISSN: 0021-9258

DOI: 10.1074/jbc.m109.011775