GLUCONEOGENESIS
o It is the process by which new glucose is synthesized from noncarbohydrate
precursors like lactate and glucogenic amino acids.
o It occurs mainly in the liver.
o Gluconeogenesis involves several enzymes of glycolysis, but it is not a
reversal of glycolysis. The irreversible steps in glycolysis are circumvented by
four enzymes which are designated as the key enzymes of gluconeo-genesis
Pyruvate Carboxylase Reaction
In the first reaction, carboxylation of pyruvate to oxaloacetate is catalyzed by the
enzyme, pyruvate carboxylase .It contains biotin which acts as a carrier of active
CO,. The reaction requires ATP. This enzyme is activated by acetyl-CoA
.
Phosphoenolpyruvate Carboxykinase
This enzyme converts oxaloacetate to phosphoenol pyruvate by losing a molecule of
CO, and adding a high energy phosphate. GTP or ITP donates the phosphate The
net effect of these two reactions is the conversion of pyruvate to
phosphoenolpyruvate, thus, circumventing the irreversible step in glycolysis
catalyzed by pyruvate kinase .
Table: Key enzymes
Irreversible steps in Corresponding key gluconeogenic
glycolysis enzymes
Pyruvate kinase Pyruvate carboxylase;
Phosphoenolpyruvate carboxykinase
Phosphofructokinase Fructose-1,6 bisphosphatase
Hexokinase Glucose-6-phosphatase
, Reversal of Glycolysis
The phosphoenol pyruvate undergoes further reactions catalyzed by the glycolytic
enzymes which are all freely reversible to form fructose-1,6 bisphosphate (glycolysis
steps 8,7,6,5 and 4).
Fructose-1,6-bisphosphatase
Fructose 1,6-bisphosphate is then acted upon by fructose 1,6-bisphosphatase to
form fructose-6 phosphate. This will bypass the step of PFK reaction (step 3 of
glycolysis).
Fructose-1,6 bisphosphate Fructose-1,6-bisphosphatase Fructose-6 phosphate + Pi
Then fructose-6-phosphate is isomerized to glucose-6-phosphate by the freely
reversible reaction catalyzed by hexosephosphate isomerase (second step in
glycolysis).
Glucose-6-phosphatase
The glucose 6-phosphate is hydrolyzed to free glucose by glucose-6-phosphatase.
Glucose-6 phosphate Glucose
Glucose-6-phosphatase is active in liver. It is absent in muscle. Therefore, only
liver can replenish blood sugar through gluconeogenesis.
ENERGY REQUIREMENT FOR GLUCONEOGENESIS
The reactions catalyzed by pyruvate carboxylase, phosphoenolpyruvate
carboxykinase and phosphor
glycerate kinase require one ATP each; so 3 ATPS are used by 1 pyruvate residue
to produce one-half molecule of glucose; or 6 ATPs are required to generate one
glucose molecule.
Glycolysis (generates 2 ATP)
Glucose Lactate
Gluconeogenesis (utilizes 6ATP)
o It is the process by which new glucose is synthesized from noncarbohydrate
precursors like lactate and glucogenic amino acids.
o It occurs mainly in the liver.
o Gluconeogenesis involves several enzymes of glycolysis, but it is not a
reversal of glycolysis. The irreversible steps in glycolysis are circumvented by
four enzymes which are designated as the key enzymes of gluconeo-genesis
Pyruvate Carboxylase Reaction
In the first reaction, carboxylation of pyruvate to oxaloacetate is catalyzed by the
enzyme, pyruvate carboxylase .It contains biotin which acts as a carrier of active
CO,. The reaction requires ATP. This enzyme is activated by acetyl-CoA
.
Phosphoenolpyruvate Carboxykinase
This enzyme converts oxaloacetate to phosphoenol pyruvate by losing a molecule of
CO, and adding a high energy phosphate. GTP or ITP donates the phosphate The
net effect of these two reactions is the conversion of pyruvate to
phosphoenolpyruvate, thus, circumventing the irreversible step in glycolysis
catalyzed by pyruvate kinase .
Table: Key enzymes
Irreversible steps in Corresponding key gluconeogenic
glycolysis enzymes
Pyruvate kinase Pyruvate carboxylase;
Phosphoenolpyruvate carboxykinase
Phosphofructokinase Fructose-1,6 bisphosphatase
Hexokinase Glucose-6-phosphatase
, Reversal of Glycolysis
The phosphoenol pyruvate undergoes further reactions catalyzed by the glycolytic
enzymes which are all freely reversible to form fructose-1,6 bisphosphate (glycolysis
steps 8,7,6,5 and 4).
Fructose-1,6-bisphosphatase
Fructose 1,6-bisphosphate is then acted upon by fructose 1,6-bisphosphatase to
form fructose-6 phosphate. This will bypass the step of PFK reaction (step 3 of
glycolysis).
Fructose-1,6 bisphosphate Fructose-1,6-bisphosphatase Fructose-6 phosphate + Pi
Then fructose-6-phosphate is isomerized to glucose-6-phosphate by the freely
reversible reaction catalyzed by hexosephosphate isomerase (second step in
glycolysis).
Glucose-6-phosphatase
The glucose 6-phosphate is hydrolyzed to free glucose by glucose-6-phosphatase.
Glucose-6 phosphate Glucose
Glucose-6-phosphatase is active in liver. It is absent in muscle. Therefore, only
liver can replenish blood sugar through gluconeogenesis.
ENERGY REQUIREMENT FOR GLUCONEOGENESIS
The reactions catalyzed by pyruvate carboxylase, phosphoenolpyruvate
carboxykinase and phosphor
glycerate kinase require one ATP each; so 3 ATPS are used by 1 pyruvate residue
to produce one-half molecule of glucose; or 6 ATPs are required to generate one
glucose molecule.
Glycolysis (generates 2 ATP)
Glucose Lactate
Gluconeogenesis (utilizes 6ATP)
