Figure: gluconeogenesis
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Function
- anabolic pathway, formation of glucose from pyruvate
Biochemistry
- in gluconeogenesis, pyruvate is converted to glucose.
- however, gluconeogenesis is not the reversal of glycolysis
- several different reactions are required because the thermodynamic equilibrium of glycolysis lies far on the side of pyruvate formation
- the actual delta G (free energy) for the formation of pyruvate from glucose is about -20 kcal/mol of glucose under typical cellular conditions
- most of the decrease in free energy takes place in 3 essentially irreversible steps catalyzed by hexokinase, phosphofructokinase & pyruvate kinase.
- in gluconeogenesis, the irreversible reactions of glycolysis are bypassed by reactions catalyzed by glucose-6-phosphatase, fructose 1,6-bisphosphatase, & a two step process bypassing pyruvate kinase catalyzed by pyruvate carboxylase & phosphoenolpyruvate carboxykinase.
- gluconeogenesis 1
- enzyme: pyruvate carboxylase
- substrate: pyruvate + CO2 + ATP + H2O
- product: oxaloacetate + ADP + H2PO4-
- gluconeogenesis 2
- enzyme: phosphoenolpyruvate carboxykinase
- substrate: oxaloacetate + GTP
- product: phosphoenolpyruvate + GDP + CO2
- gluconeogenesis 3
- enzyme: enolase
- substrate: phosphoenolpyruvate
- product: 2-phosphoglycerate
- gluconeogenesis 4
- enzyme: phosphoglycerate mutase
- substrate: 2-phosphoglycerate
- product: 3-phosphoglycerate
- gluconeogenesis 5
- enzyme: phosphoglycerate kinase
- substrate: 3-phosphoglycerate + ATP
- product: 1,3-diphosphoglycerate + ADP
- gluconeogenesis 6
- enzyme: glyceraldehyde-3-phosphate dehydrogenase
- substrate: 1,3-diphosphoglycerate + NADH
- product: glyceraldehyde-3-phosphate + NAD+ + H2PO4-
- gluconeogenesis 7
- enzyme: triosephosphate isomerase
- substrate: glyceraldehyde-3-phosphate
- product: dihydroxyacetone phosphate)
- gluconeogenesis 8
- gluconeogenesis 9
- enzyme: fructose-1,6-bisphosphatase
- substrate: fructose-1,6-diphosphate + H2O
- product: fructose-6-phosphate + H2PO4-
- gluconeogenesis 10
- enzyme: phosphohexose isomerase
- substrate: fructose-6-phosphate
- product: glucose-6-phosphate
- gluconeogenesis 11
- enzyme: glucose-6-phosphatase
- substrate: glucose-6-phosphate + H2O
- product: glucose + H2PO4-