What does PEPCK do in gluconeogenesis?

Phosphoenolpyruvate carboxykinase (PEPCK) is an enzyme in the lyase family used in the metabolic pathway of gluconeogenesis. It converts oxaloacetate into phosphoenolpyruvate and carbon dioxide. It is found in two forms, cytosolic and mitochondrial.

How was the PEPCK Cmus mice genetically modified?

1.32) (PEPCK-C) in skeletal muscle, PEPCK-Cmus mice were created by introducing the cDNA for the enzyme, linked to the human α-skeletal actin gene promoter, into their germ line. These mice live longer than controls and the females remain reproductively active for as long as 35 months.

Where in the cell does PEPCK perform phosphorylation?

PEPCK is phosphorylated in the cotyledons of all germinating seedlings and leaves of PEPCK-type CAM plants studied (Walker and Leegood, 1995; Walker et al., 1997).

How is PEPCK regulation?

Acute regulation of PEPCK is achieved by modulating transcription of the gene, which is tightly regulated by cAMP (the mediator of glucagon and catecholamines), glucocorticoids and insulin.

What is the role of PEPCK?

PEPCK is a gluconeogenic enzyme that allows hepatic parenchymal cells to produce glucose from pyruvate derived from amino acid metabolism.

What are two pathways in which PEPCK is an important enzyme?

The role of PEPCK-C in hepatic and renal gluconeogenesis has been extensively reviewed (6), as have the factors that control transcription of its gene in these tissues (7).

Which hormone is responsible for direct activation of PEPCK by phosphorylation?

Under fasting conditions, the increased secretion of pancreatic glucagon activates PKA, which in turn phosphorylates CREB, leading to an increased association of CREB with its co-activators CRTC2 and CBP/p300 onto the chromatin.

Does insulin inhibit PEPCK?

Insulin can also potently and rapidly (within minutes) inhibit the transcription of phosphoenolpyruvate carboxykinase (PEPCK), an enzyme that has long been thought of as the rate-determining enzyme controlling GNG flux to G6P.

Is PEPCK sensitive to temperature?

Temperature curves of the three PEPCK reactions indicate optimum activities between 38 and 45 C. Below 30 C the energy of activation was 8.2 kcal/mol for the decarboxylation reaction.

Why is PEPCK important?

PEPCK should be viewed as a cataplerotic enzyme because it plays the important role of removing citric acid cycle anions for either the biosynthetic process or the subsequent complete oxidation of the these compounds to carbon dioxide in the citric acid cycle.

What is the role of Pepck?

Why does insulin inhibit gluconeogenesis?

A significant mechanism through which insulin is able to modulate STAT3 activity is its hypothalamic action. Insulin action in the hypothalamus stimulates IL-6 production in the liver, and IL-6 in turn suppresses gluconeogenesis by activating STAT3.