Gluconeogenesis is the production of glucose from non-carbohydrate sources through a complex series of metabolic pathways. It occurs primarily in the liver and kidney cytosol and produces approximately 1 kg of glucose per day, which is essential for brain function and as an energy source for muscles. The major precursors for gluconeogenesis are lactate, pyruvate, amino acids, glycerol, and propionate derived from the breakdown of proteins, fats, and certain metabolites. The pathways involved closely mirror glycolysis except for a few irreversible steps that are bypassed by alternative enzyme-catalyzed reactions in order to synthesize glucose from these precursors.

1. GLUCONEOGENESIS
Mrs.Kalaivani sathish , M.pharm,

2. INTRODUCTION
• The production of glucose from non –
carbohydrate compounds is known as
gluconeogenesis.
• Lactate, pyruvate, glucogenic amino
acids, propionate and glycerol are the
major precursors for gluconeogenesis

3. LOCATION OF
GLUCONEOGENESIS
• Gluconeogenesis occurs mainly in the
cytosol.
• About 1 kg of glucose is produced everyday.

4. IMPORTANCE OF
GLUCONEOGENESIS
• Glucose is a very key substance for the
metabolism and its continuous supply
is essential to the body for a variety of
functions.
• Human brain alone requires about 120
g of glucose per day, out of 160 g
needed by the entire body.

5. • Glucose is the only source that supplies
energy to the skeletal muscles under
anaerobic conditions.
• Gluconeogenesis helps in clearing certain
metabolites produced in the tissues, which
accumulates in the blood. e.g. lactate,
glycerol, propionate etc.

6. • The degradation of glycogen in muscle
results in the formation of lactate.
Breakdown of fat in adipose tissue will
produce free glycerol and propionate.
• Lactate, glycerol, propionate and some
amino acids are good precursors for
glucose synthesis.
• Gluconeogenesis continuously add glucose
to the blood.
• Cori cycle is responsible for the conversion
of muscle lactate to glucose in liver.

7. REACTIONS OF
GLUCONEOGENESIS
• Gluconeogenesis closely resembles the
reversed pathway of glycolysis.
• In glycolysis all the reactions, except three
are reversible. These includes,
• Pyruvate to Phosphoenol Pyruvate
• Fructose – 1,6 bisphosphate to Fructose 6 –
phosphate
• Glucose 6 – phosphate to glucose

9. Conversion of Pyruvate
to
Phosphoenol Pyruvate
• This takes place in two steps
• Step – 1: Pyruvate carboxylase is a
biotin dependent mitochondrial enzymes
that converts pyruvate to
oxaloacetate in presence of ATP and
CO2.
• Oxaloacetate is synthesized in the
mitochondrial matrix. It has to be
transported to the cytosol to be used in the
gluconeogenesis.

10. • Due to the membrane impermeability,
oxaloacetate cannot diffuse out of
mitochondria.
• The oxaloacetate is firstly converted into
malate and then transported to the cytosol.
Within the cytosol, the oxaloacetate is
regenerated.
• Malate dehydrogenase is the enzyme helps
in the reconversion of oxaloacetate.

11. • In the cytosol, the enzyme Phosphoenol
pyruvate carboxykinase converts
oxaloacetate to phosphoenol pyruvate.
• Step – 2: Conversion of fructose 1,6-
bisphosphate to fructose 6-phosphate: the
enzyme fructose 1,6-bisphosphatase
converts fructose 1,6-bisphosphate to
fructose 6-phosphate.

12. • Step 3: Conversion of glucose 6
– phosphate to glucose:
enzyme glucose 6-phosphatase
catalyses the conversion of
glucose 6 – phosphate to glucose

13. GLUCONEOGENESIS FROM
AMINO ACIDS
• Glucose is synthesized from the
Pyruvates and the intermediates of
the citric acid cycle.

14. GLUCONEOGENESIS FROM
GLyCEROL
• On hydrolysis of fats in adipose tissue glycerol is
obtained.
• Glycerol is converted to glycerol 3 – phosphate by
an enzyme glycerokinase.
• Dihydroxy acetone phosphate is formed from
glycerol 3 – phosphate , by an enzyme called
glycerol 3 – phosphate dehydrogenase.
• Dihydroxy acetone phosphate is an intermediates
of Glycolysis which can be used for glucose
production.

15. GLUCONEOGENESIS FROM
PROPIONAtE
• Three carbon propionyl CoA is produced by the
oxidation of fatty acids and breakdown of some
amino acids.
• Propionyl CoA Carboxylase acts in the presence
of ATP and biotin and converts to Methyl Malonu
Co A, which is then converted into Succinyl Co A,
in presence of B 12 coenzyme.
• Succinyl Co A then enters gluconeogenesis via
citric acid cycle.

16. GLUCONEOGENESIS FROM
LACTATE

17. GLUCONEOGENESIS FROM
LACTATE
• Any activity involving the muscles requires
energy, which comes in the form of Adenosine
triphosphate (ATP) once it is converted from
glycogen through the processes of glycogenolysis
and glycolysis.
• When there is a lack of an adequate oxygen
supply, typically the result of any intense muscular
activity such as running; energy is released
through “anaerobic metabolism”.

18. GLUCONEOGENESIS FROM
LACTATE
• Lactate, produced through the “lactic acid
fermentation” is absorbed by liver and converted
back into pyruvate and then into glucose.
• This glucose can then be used to replenish the
levels of glycogen via “glycogenesis” and in turn,
provide ATP via glycolysis once the muscular
activity has ceased.Is called “gluconeogenesis”.

19. GLUCOSE ALANINE CYCLE
• There is a continuous transport of amino acids
from muscle to liver.
• This is occurring during starvation.
• Alanine is the major amino acids.
• pyruvate in skeletal muscle that undergoes
transamination to produce alanine.
• Alanine is transported to liver and used for
gluconeogenesis. This cycle is referred to as
glucose alanine cycle.