Gluconeogenesis is the process by which glucose is synthesized from non-carbohydrate precursors like lactate, glycerol, and certain amino acids. It occurs primarily in the liver and involves bypassing the three irreversible steps of glycolysis through different enzymes. Key enzymes in gluconeogenesis include pyruvate carboxylase and PEP carboxykinase which catalyze reactions to bypass pyruvate kinase. Gluconeogenesis and glycolysis share certain intermediate compounds but are not simple reversals of each other due to different enzymatic pathways. Regulation of these two processes helps determine whether glucose or glycogen will be synthesized or broken down depending on the body's energy needs.

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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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