Gluconeogenesis Biochemistry - Dr G Bhanu Prakash

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Gluconeogenesis from Pyruvate : Medical Biochemistry - Dr G Bhanu Prakash

Gluconeogenesis is the process of synthesizing glucose from noncarbohydrate precursors.
The major substrates are the glucogenic amino acids, lactate, glycerol, and propionate.
The liver and kidneys are the major gluconeogenic tissues.
Glucocorticoids and glucagon-stimulated cAMP induce synthesis of key enzymes of gluconeogenesis.
Hexokinase, phosphofructokinase, and pyruvate kinase are the steps in glycolysis differing from gluconeogenesis. These steps are replaced by glucose-6-phosphatase; fructose-1,6-bisphosphatase; and a combination of pyruvate carboxylase and PEP carboxykinase, respectively.
No cell in the human body can have both glycolysis and gluconeogenesis working alongside each other because of the opposing hormonal and allosteric regulators of these cycles.
PFK-1 is allosterically activated by a high concentration of AMP and ADP, but the most potent activator is fructose-2,6-bisphosphate.
PFK-1 is inhibited by glucagon through repression of synthesis and by citrate and ATP.
Glucagon-stimulated cAMP-dependent protein kinase inactivates phosphofructokinase-2 and activates fructose-2,6-bisphosphatase by phosphorylation.
Insulin-mediated increase in fructose-2,6-bisphosphate activates phosphofructokinase-1 and inhibits fructose 1,6-bisphosphatase.
Glucokinase-regulatory protein (GKRP) maintains an inactive reserve of glucokinase. This glucokinase reserve is used in response to increasing levels of portal vein glucose, favoring glycolysis.

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