How has PEPCK Cmus mice been 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.
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 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.
Why is phosphoenolpyruvate carboxykinase 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.
How do Pepck Cmus mice help?
They added that this indicates that the PEPCK-Cmus mice relied heavily on fatty acids as a source of energy during exercise, while the control animals rapidly switched from fatty acid metabolism to using muscle glycogen (carbohydrates) as a fuel; this dramatically raised the blood lactate levels.
Where is PEPCK located?
To evaluate published indications that about 25% of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK), is located in mitochondria of adult rat liver, cell fractionations were conducted with hepatocytes isolated from rats that were fed ad libitum or starved for 2 days.
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.
What is the function of phosphoenolpyruvate?
Phosphoenolpyruvate acts as the second source of ATP in glycolysis. The transfer of the phosphate group from PEP to ADP, catalyzed by pyruvate kinase , is also highly exergonic and is thus virtually irreversible under…
What is phosphoenolpyruvate used for?
It has the highest-energy phosphate bond found (−61.9 kJ/mol) in organisms, and is involved in glycolysis and gluconeogenesis. In plants, it is also involved in the biosynthesis of various aromatic compounds, and in carbon fixation; in bacteria, it is also used as the source of energy for the phosphotransferase system.
What are the obvious effects of the Pepck overexpression?
We conclude that overexpression of PEPCK-C repatterns energy metabolism and leads to greater longevity. PEPCK-C2 is involved in gluconeogenesis in the liver and kidney cortex and in glyceroneogenesis in liver and white and brown adipose tissue (see Ref. 1 for a review).
Does PEPCK use ATP?
In bacteria, fungi and plants, PEPCK is involved in the glyoxylate bypass, an alternative to the tricarboxylic acid cycle. This entry represents ATP-utilising phosphoenolpyruvate carboxykinase enzymes.