3. Definition
• Gluconeogenesis is a major regulatory process
in the liver and kidneys by which
noncarbohydrate substrates; namely glycerol,
lactate, propionate, and glucogenic amino
acids; are converted to glucose 6-phosphate
(Glc-6-P), and then to either free glucose or
glycogen
4. Site
• The liver and kidneys are the major organs
containing the full complement of
gluconeogenic enzymes (i.e., pyruvate
carboxylase, PEP carboxykinase, fructose 1,6-
bisphosphatase, and glucose 6-phosphatase)
• It occurs in all animal ,plants ,fungi and micro-
organism.
5.
6. Reaction of Gluconeogenesis
• Gluconeogenesis and glycolysis are not
identical pathways running in opposite
directions,although they do share several
steps .
• 7 out of 10 enzymatic reactions of
gluconeogenesis are reverse of glycolytic
reaction.
• Three reactions of glycolysis are esentially
irreversible .
9. Reaction of Gluconeogenesis
• Three irreversible steps are –
1.Conversion of glucose 6 phosphate catalyzed
by hexokinase.
2.The conversion of fructose 6-phosphate to
fructose 1,6 bis phosphate by PFK-1.
3.The conversion of phosphoenol pyruvate by
pyruvate kinase.
10. Reaction of Gluconeogenesis
• These three reactions are characterized by a
large negative free energy change ,where as
other glycolytic reaction have ΔG near 0.
• In Gluconeogenesis these irreversible steps
are bypassed by a separate set of enzymes.
11. Reaction of Gluconeogenesis
conversion of Pyruvate to PEP
• Pyruvate can not be converted directly to PEP.
The conversion requires two reactions that
serve to bypass irreversible step of glycolysis.
• Pyruvate is first transported from the cytosol
into mitochondria or is generated from
alanine within mitpchondria by
transamination.
12. Reaction of gluconeogenesis
• Then pyruvate carboxylase ,mitochondrial
enzyme that requires the coenzyme
biotin,converts pruvate to oxaloacetate.
•
Pyruvate+Hco3-+ATP
oxaloacetate+ADP+Pi
13. Reaction of gluconeogenesis
• Oxaloacetate cannot directly cross the inner
mitochondrial membrane. Therefore, it is
converted to malate or to aspartate, which can
cross the mitochondrial membrane and be
reconverted to oxaloacetate in the cytosol.
• Oxaloacetate is decarboxylated by
phosphoenolpyruvate carboxykinase to form
phosphoenolpyruvate. This reaction requires
GTP.
14. Reactions of Gluconeogenesis
• Phosphoenolpyruvate is converted to fructose
1,6-bisphosphate by reversal of the glycolytic
reactions.
15. Reactions of Gluconeogenesis
Conversion of 1,6 BP to F-6 P
• Second bypass reaction.
• Fructose-1, 6-bisphosphate is converted to
fructose-6-phosphate in a reaction that
releases inorganic phosphate and is catalyzed
by fructose-1,6-bisphosphatase.
• The highly exergonic irreversible reaction is
catalyzed by Fructose 1,6bisphosphatase.
16. Reactions of Gluconeogenesis
(Conversion of G-6 P to Glucose)
• Third bypass.
• Glucose-6-phosphate releases inorganic
phosphate, which produces free glucose that
enters the blood. The enzyme involved is
glucose 6-phosphatase.
17. Net requirements to make one glucose
molecule
• Thus, the net requirements to make one
glucose molecule are:
• Two pyruvate.
• Four ATP and two GTP.
• Two NADH.
• Six H2O
•
18. Significance
• Gluconeogenesis is needed to meet the
demands for plasma glucose between meals,
which then becomes particularly important as
an energy substrate for nerves, erythrocytes,
and other largely anaerobic cell types. Failure
of this process can lead to brain dysfunction,
coma, and death.
