1. CHAPTER 17
Gluconeogenesis

2. Gluconeogenesis The Liver and kidney can synthesize glucose from
noncarbohydrate precursors such as lactate, alanine and glycerol
Under fasting conditions, and when glycogen reserves are low,
gluconeogenesis supplies almost all of the body’s glucose
2 Pyruvate NADH ATP GTP H2O H+
Glucose NAD ADP GDP Pi
Biosynthesis of glucose requires energy in the form of ATP equivalents and NADH

3. The placement of glycerol (from triglyceride breakdown)
into glycolysis or gluconeogenesis.
Triose phosphate isomerase
DHAP can be used
for glycolysis or
gluconeogenesis

4. Figure 17.1: Comparison of
Gluconeogenesis and Glycolysis
- NOT a complete reversal of
glycolysis.
Irreversible reactions in glycolysis
cannot be utilized for
gluconeogenesis
- Unique enzymatic reactions are
needed for the three irreversible
reactions of glycolysis:
hexokinase
PFK-1
pyruvate kinase
All seven near equilibrium
reactions of glycolysis proceed
in reverse.

5. Figure 17.2: Carboxylation of pyruvate requires the coenzyme biotin
Bicarbonate (HOCO2-) is first phosphorylated using ATP
to make HOCO2-PO32-
Biotin-enzyme + HOCO2-PO32- makes
CO2-biotin-enzyme + Pi
CO2-biotin-enzyme + pyruvate makes biotin-enzyme
+ oxaloacetate
biotin

6. Figure 17.1: Comparison of
Gluconeogenesis and glycolysis
- NOT a complete reversal of
glycolysis.
Irreversible reactions in glycolysis
cannot be utilized for
gluconeogenesis
- Unique enzymatic reactions are
needed for the three irreversible
reactions of glycolysis:
hexokinase
PFK-1
pyruvate kinase
All seven near equilibrium
reactions of glycolysis proceed
in reverse.

7. Fructose 1,6-bisphosphatase (F1,6BPase)
Catalyzes a metabolically irreversible reaction
F1,6BPase is allosterically inhibited by AMP and
fructose 2,6-bisphosphate (strong activator of PFK-1)

8. Glucose 6-phosphatase
Catalyzes a metabolically irreversible hydrolysis reaction
In most cases, the biosynthesis ends with glucose
6-phosphate where it becomes the active substrate
for pathways leading to glycogen, starch, and pentose sugar
synthesis
Glucose is an important end product when other tissue need
an energy source for glycolysis. This takes place largely in the liver.

9. Figure 17.3: The conversion of pyruvate To oxaloacetate.
Pyruvate translocase
Pyruvate
Glucose
Figure 17.3: The conversion of pyruvate
To oxaloacetate.
The conversion takes place in the
mitochondrial matrix.
Oxaloacetate is reduced to malate
before transport into the cytoplasm.
- malate is then oxidized back to oxaloacetate.

10. Figure 17.5 Reciprocal regulation in the liver Allosteric activators
When glucose is abundant, glycolysis dominates
When glucose is scarce,
gluconeogenesis will take over
Allosteric
activators
Allosteric
inhibitors
Allosteric
inhibitors
Allosteric
activators
Allosteric
inhibitors
Allosteric
activators
Allosteric
inhibitors
Allosteric
activators
Figure 17.5

11. Fructose 2,6-bisphosphate is produced by PFK-2
Recall that F-2,6-BP is a powerful activator of PFK (or PFK-1) in glycolysis
Phosphofructokinase 2 (PFK-2) synthesizes F-2,6,BP, BUT it also breaks down F-2,6-BP
when glycolysis must be slowed. PFK-2 and FBPase2 (fructose 2,6-bisphophatase)
are different enzyme activities found on the SAME protein molecule.
FBPase2
domain
PFK2
domain

12. Figure 17.7: synthesis and breakdown of fructose 2,6-bisphosphate
After times of Feasting
Insulin is secreted by the pancreas
Production of F-2,6-BP
increases

13. Figure 17.7: synthesis and breakdown of fructose 2,6-bisphosphate
After times of Fasting
Glucagon is secreted by the pancreas
Conc. of F-2,6-BP
must decreases

14. The interaction of glycolysis and gluconeogenesis
Lactate metabolism during high anaerobic activity
Glycolysis generates large amounts of lactate in active muscle
Liver lactate dehydrogenase converts lactate to pyruvate
(a substrate for gluconeogenesis)
Glucose produced by the liver is delivered back to muscles
via the bloodstream
Figure 12.2
Cori cycle: glucose catabolism to L-lactate in peripheral tissues, delivery of lactate to the liver, formation of glucose from lactate in the liver, and delivery of glucose back to peripheral tissues.
Figure 17.10
The Cori Cycle
The interaction of glycolysis and gluconeogenesis

15. Assignment
Read Chapter 17
Read Chapter 18