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Gluconeogenesis
Mainly occurs in cytosol
Some precursors are produced in mitochondria
Takes place in liver and kidney
Synthesis of glucose or glycogen from non
carbohydrates like pyruvate, lactate glucogenic
amino acids, glycerol and propionic acid
Pathway involves steps of TCA cycle and reversal of
glycolysis
The irreversible steps of glycolysis are catalysed by
 Hexokinase
 Phosphofructokinase and
 Pyruvate kinase
These three stages bypassed by alternate enzyme
specific to gluconeogenesis
They are called as key enzymes of gluconeogenesis
1. Pyruvate carboxylase
2. Phosphoenolpyruvate carboxykinase (PEPCK)
3. Fructose 1,6- Bis phosphatase
4. Glucose 6-phosphatase
The pathway meet the needs of the body for
glucose
Continuos supply of glucose required as a source
of energy for the CNS, Brain, RBC and skeletal
muscle during starvation
Substrates for Gluconeogenesis
Gly, Ala, Ser, Thr, Cys, Trp  pyruvate oxaloacetate
Phe, Tyr, fumarate
Asp, Asn
Arg, His,Glu, gln, proKGoxaloacetateGlucose
Val, isoleucine, Met  succinyl CoA
Propionyl CoA  succinyl CoA  oxaloacetate
Cori’s Cycle
Glucose/Glycogen converted to lactate in
the muscle and this lactate is converted
back to glucose in liver
During active muscle contraction glycogen
breaks down to generate glucose
Regulation of gluconeogenesis
The glucagon and the availability of substrates mainly
regulate gluconeogenesis
Glucagon & glucocorticoid  gluconeogenesis.
Insulin inhibit gluconeogenesis
Glucogenic amino acids have stimulating effect on key
gluconeogenic enzymes
* Acetyl CoA promotes gluconeogenesis
Starvationexcessive lipolysis in adipose
tissues acetyl CoA accumulates in the liver, acetyl CoA stimulate
gluconeogenic enzymes.