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.