Gluconeogenesis: Glucose Synthesis

1. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
22.7 Gluconeogenesis: Glucose Synthesis
Learning Goal Describe how glucose is synthesized from
noncarbohydrate molecules.
Glucose is
synthesized in the
tissues of the liver
and kidneys.
Tissues that use
glucose as their main
energy source are
the brain, skeletal
muscles, and red
blood cells.

2. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Utilization of Glucose
Glucose is the primary energy source for the brain,
skeletal muscle, and red blood cells. Glucose
deficiency can impair the brain and nervous system.
If our glycogen stores are depleted,
• liver cells synthesize glucose by gluconeogenesis.
• glucose is synthesized in the cytosol of the liver
cells, and some is synthesized in the kidneys.

3. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Glycogen
Glycogen
• can supply us with about one day’s requirement of
glucose.
• is made from glucose, most of which is synthesized
in the cytosol of liver cells.
To begin gluconeogenesis, carbon atoms from
noncarbohydrate food sources are converted to
pyruvate.

4. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Pyruvate to Phosphoenolpyruvate
To start the synthesis of glucose from pyruvate,
• two catalyzed reactions are needed to replace reaction
10 in glycolysis.
• pyruvate carboxylase uses the energy of ATP
hydrolysis to catalyze the addition of CO2 to pyruvate
and produce oxaloacetate.
• phosphoenolpyruvate carboxykinase converts
oxaloacetate to phosphoenolpyruvate.
• phosphoenolpyruvate molecules now use enzymes to
form fructose-1,6-bisphosphate.

5. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Pyruvate to Phosphoenolpyruvate

6. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Fructose-1,6-Bisphosphate to Fructose-6-
Phosphate
The second irreversible reaction in glycolysis is bypassed when
fructose-1,6-bisphosphatase cleaves a phosphate group from
fructose-1,6-bisphosphate.
The product fructose-6-phosphate undergoes the reversible
reaction 2 of glycolysis to yield glucose-6-phosphate.

7. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Glucose-6-Phosphate to Glucose
In the final irreversible reaction, the phosphate group of
glucose-6-phosphate is hydrolyzed by a different enzyme,
glucose-6-phosphatase, to form glucose.

8. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Glycolysis and Gluconeogenesis

9. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Energy Cost of Gluconeogenesis
• The pathway consists of seven reversible reactions
of glycolysis and four new reactions that replace
the three irreversible reactions.
• Overall, glucose synthesis requires 4 ATPs,
2 GTPs, and 2 NADHs.

10. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Lactate and the Cori Cycle
The Cori cycle
• is the flow of lactate and glucose between the
muscles and the liver.
• occurs when anaerobic conditions occur in active
muscle, and glycolysis produces lactate.
• operates when lactate moves through the blood
stream to the liver, where it is oxidized back to
pyruvate.
• converts pyruvate to glucose, which is carried back
to the muscles.

11. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Lactate and the Cori Cycle

12. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Regulation of Gluconeogenesis
Gluconeogenesis is
• not utilized when the diet is high in carbohydrates.
• very active when the diet is low in carbohydrates.
When conditions in a cell favor glycolysis, there is no
synthesis of glucose.
When the cell requires the synthesis of glucose,
glycolysis is turned off.

13. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Regulation, Glycolysis, and
Gluconeogenesis

14. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Metabolic Reactions of Glucose
Glycolysis involves the breakdown of glucose, and gluconeogenesis involves the synthesis of
glucose from noncarbohydrates. The pentose phosphate pathway converts glucose to ribose
and provides NADPH. Glycogenolysis degrades glycogen to glucose whereas glycogenesis
produces glycogen from glucose.

15. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Study Check
Identify each process.
1) glycolysis 2) glycogenesis
3) glycogenolysis 4) gluconeogenesis
A. the synthesis of glucose from
noncarbohydrates
B. the breakdown of glycogen
into glucose
C. the oxidation of glucose to
two pyruvate
D. the synthesis of glycogen
from glucose

16. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Solution
Identify each process.
1) glycolysis 2) glycogenesis
3) glycogenolysis 4) gluconeogenesis
A. the synthesis of glucose from
noncarbohydrates 4) gluconeogenesis
B. the breakdown of glycogen
into glucose 3) glycogenolysis
C. the oxidation of glucose to
two pyruvate 1) glycolysis
D. the synthesis of glycogen
from glucose 2) glycogenesis

17. General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Concept Map