Gluconeogenesis

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2.  Gluconeogenesis makes glucose from
non-carbohydrate starting materials
◦ Lactate
◦ Glycerol
◦ Most amino acids (not leucine, lysine)
◦ Glycerol and amino acids are used only in
starvation conditions
 Process occurs primarily in the liver
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3. The gluconeogenic pathway converts pyruvate
into glucose.
pyruvate glucose→→ → → →
gluconeogenesis
glycolysis
Gluconeogenesis is not a reversal of
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4.  While basically opposite processes
glycolysis and gluconeogenesis are not a
simple reversal of each other
 The three nonreversible steps of
glycolysis must be bypassed with new
routes
◦ Pyruvate  Phosphoenolpyruvate
◦ Fructose-1,6-bisphosphate  Fructose-6-
phosphate
◦ Glucose-6-phosphate  Glucose
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6. •The two enzymes that catalyze the reactions for
bypass of the Pyruvate Kinase reaction are the
following:
•Pyruvate Carboxylase (Gluconeogenesis) catalyzes:
pyruvate + HCO3
- + ATP  oxaloacetate + ADP + Pi
•PEP Carboxykinase (Gluconeogenesis) catalyzes:
oxaloacetate + GTP  PEP + GDP + CO2
C
C
CH2
O O-
OPO3
2-
C
C
CH3
O O-
O
ATP ADP + Pi C
CH2
C
C
O
O O-
O-
O
HCO3
-
GTP GDP
CO2
pyruvate oxaloacetate PEP
Pyruvate Carboxylase PEP Carboxykinase
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7.  Fructose 6-phosphate is formed from
1,6-bisphosphate by hydrolysis of the
phosphate ester at carbon1.
 Fructose 1,6-bisphosphatase catalyzes
this exergonic hydrolysis
Fructose 1,6-bisphosphate + H2O 
fructose 6-phosphate + Pi
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8.  Glucose is formed by the hydrolysis of
gulcose 6-phosphate in a reaction
catalyzed by gulcose 6-phosphatase
Gulose 6-phosphate + H2O 
gulcose + Pi
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9. Glyceraldehyde-3-phosphate
Dehydrogenase
Phosphoglycerate Kinase
Enolase
PEP Carboxykinase
glyceraldehyde-3-phosphate
NAD+
+ Pi
NADH + H+
1,3-bisphosphoglycerate
ADP
ATP
3-phosphoglycerate
Phosphoglycerate Mutase
2-phosphoglycerate
H2O
phosphoenolpyruvate
CO2 + GDP
GTP
oxaloacetate
Pi + ADP
HCO3
-
+ ATP
pyruvate
Pyruvate Carboxylase
Gluconeogenesis
Summary of
Gluconeogenesis
Pathway:
Gluconeogenesis
enzyme names in
red.
Glycolysis enzyme
names in blue.
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10. Glucose-6-phosphatase
Fructose-1,6-bisphosphatase
glucose Gluconeogenesis
Pi
H2O
glucose-6-phosphate
Phosphoglucose Isomerase
fructose-6-phosphate
Pi
H2O
fructose-1,6-bisphosphate
Aldolase
glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate
Triosephosphate
Isomerase
(continued)
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11.  Step 3 of glycolysis:
◦ Catalyzed by phosphofructokinase
◦ Stimulated by: high AMP, ADP, Pi
◦ Inhibited by: high ATP
 Reverse occurs in gluconeogenesis:
◦ Fructose-1,6-bisphosphatase stimulated by
high ATP
◦ At times of excess energy (high ATP)
gluconeogenesis is favored
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12. Reciprocal regulation of
gluconeogenesis and glycolysis in
the liver.
The interconversion of
fructose 6-phosphate
and fructose 1,6-
bisphosphate
is stringently controlled
The interconversion of
phosphoenolpyruvate
and pyruvate also is
precisely
regulated.
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13.  In the Cori cycle,
◦ Lactate from skeletal muscle is transferred
to the liver
◦ Converted to pyruvate then glucose
◦ This glucose can be returned to the muscle

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