Gluconeogenesis is the formation of glucose from non-carbohydrate sources like amino acids, lactate, glycerol, and propionate. It occurs primarily in the liver and some tissues during periods of fasting or low carbohydrate intake to ensure glucose availability. Key reactions include the conversion of pyruvate to phosphoenolpyruvate and fructose-1,6-bisphosphate to fructose-6-phosphate to ultimately form new glucose molecules from these precursors.

1. GLUCONEOGENESIS
BY:
SATHISH RAJAMANI
ASSOCIATE PROFESSOR

2.  Also known as “Neoglucogenesis”.
 It is the formation of glucose from various non – carbohydrate
sources.
 Non Carbohydrate sources includes: glucogenic amino acids,
lactate, glycerol or propionate.
DEFINITION

3.  Gluconeogenesis takes place in the fasting state or on
a low carbohydrate diet.
 Site of gluconeogenesis is “ Liver and Some Tissues”.
 Gluconeogenesis ensures the availability of glucose to
our body when all the dietary glucose has been
absorbed and oxidized.

4.  Conversion of Pyruvate to Phosphophenol
Pyruvate.
 Conversion of Fructose 1,6-Bisphosphate to
Fructose 6 – Phosphate.
 Conversion of Glucose 6 – Phosphate to Glucose.
GLUCONEOGENESIS
REACTIONS

5.  Step -1: Pyruvate is first converted to oxaloacetate by the enzyme
Pyruvate carboxylase, in mitochondria.
 Step – 2: Malate dehydrogenase converts oxaloacetate to malate.
 Malate thus formed inside mitochondria is now freely transported
across the mitochondrial membrane and comes into cytosol, here it
is again converted into oxaloacetate by the same enzyme.
PYRUVATE
To
PHOSPHOENOL PYRUVATE

6.  Step – 3: In the cytosol the enzyme phosphoenolpyruvate
carboxykinase coverts oxaloacetate to phosphoenol pyruvate.
 Pyruvate Oxaloacetate
 Pyruvate Carboxylase PEP - Carboxykinase
Oxaloacetate Phosphoenol Pyruvate
PYRUVATE
To
PHOSPHOENOL PYRUVATE

7. Fructose- 1,6-bisphosphate
H2O
Pi Fructose – 1,6 biphosphatase
Fructose – 6 – Phosphate
Fructose-1,6-bisphosphate is converted to fructose-6-
phosphate by the enzyme fructose-1, 6-bisphosphatase.
CONVERSION OF
Fructose-1,6-Biphosphate
to
Fructose- 6- phosphate

8. Glucose-6-phosphate
H2O
Glucose-6- phosphatase
Pi
Glucose
Glucose-6-phosphate is converted to glucose by the
enzyme glucose-6-phosphatase.
CONVERSION
OF
GLUCOSE-6-PHOSPHATE TO GLUCOSE

9.  LACTATE
 GLYCOGENIC AMINO ACID
 GLYCEROL
 PROPIONATE
SUBSTRATES FOR
GLUCONEOGENESIS

10.  Lactate is produced during the process of anaerobic
glycolysis.
 This is converted into glucose in two steps.
 Firstly lactate is oxidized to pyruvate. This reaction is
catalysed by an enzyme lactate dehydrogenase.
 Subsequently the lactate is converted into glucose by the
reversal of glycolytic reactions.
LACTATE

11. Lactate
NAD+
NADH + H+ Lactate dehydrogenase
Pyruvate
Glucose
LACTATE

12.  In the liver, various glucogenic amino acids transfer their α –
amino group by transamination and release carbon skeleton,
which forms intermediates of the citric acid cycle.
 These citric acid cycle intermediates in turn can form glucose
by reversal of the glycolytic reactions via pyruvate.
GLYCOGENIC AMINO ACID

13.  Glycolysis is produced as a result of lipolysis in
adipose tissue.
 Glyceral kinase converts it to α – glycerolphosphate
in the liver which is later reduced by a
dehydrogenase to dihydroxy – acetone phosphate
and can enter glycolysis at this point.
GLYCEROL

14.  Propionyl CoA is obtained from Ile, Val and Thr.
 It is converted to D – methylmalonyl CoA by Propionyl CoA
carboxylase.
 D – Methylmalonyl CoA is then converted to L-Methylmalonyl CoA
and finally, by an isomerase to Succinyl CoA, which is an
intermediate of the citric acid cycle.
 Succinyl CoA in turn can be converted to glucose Via Pyruvate.
PROPIONATE

15. Propionyl CoA Carboxylase
Propionyl CoA D – Methylmalonyl CoA
Isomerase
L – Methymalonyl CoA Succinyl CoA
B12
Glucose

16.  The glucose is thus produced from various non –
carbohydrate sources such as lactate, glycogenic
amino acid, glycerol and propionate.
SUMMARY