1. Introduction of Glucose Metabolism Lecture-4
GLUCONEOGENESIS  

2. GLUCONEOGENESIS  
Gluconeogenesis is the synthesis of glucose from glucogenic precursors
which are not of carbohydrate origin (gluconeogenic precursors)
It occurs during prolonged fasting to synthesize glucose for tissues
requiring continuous supply of glucose as a source of energy:
Brain, RBCs, Kidney medulla, Lens, Cornea, Testes, sk.ms
Gluconeogenesis occurs ONLY in the liver & kidneys

3. Gluconeogenic precursors
1- Intermediates of glycolysis
by reverse of steps of glycolysis (except 4 steps that need 4 different enzymes)
2- Intermediates of citric acid cycle
are converted to oxalacetate then to glucose
3- Lactate
Lactic acid formed of anaerobic glycolysis in cells as RBCs & skeletal muscles
are transported in blood to liver to be converted to pyruvate then to glucose (Cori cycle)
4- Glycerol
Glycerol is derived from the lipid triacylglycerol in adipose tissue.
Glycerol is convered into dihydroxyactone phosphate (intermediate of
glycolysis) then to glucose.
5- Glucogenic amino acids of proteins
Glucogenic amino acids are deaminated to form a-ketoacids
a-keto acids are converted to pyruvate or intermediates of citric acid cycle then to glucose

4. GLUCOSE Triacylglycerol in adipose tissue Precursors of
Gluconeogenesis
Fatty acids
Gluconeogenesis
Glycerol
Lactate
Oxalacetate
Pyruvate
Intermediate of
CITRIC ACID CYCLE
Glucogenic amino acids
in proteins as sk. ms.

5. Glycerol as a gluconeogenic Substrate
Kinase
Glycerol
Glycerol 3-phosphate
ATP
ADP
NAD+
Glycerol 3-phosphate
dehydrogenase
NADH
Glucose
Dihydroxyacetone phosphate
GK: Glycerol kinase only in liver & kidneys

6. Glucogenic Amino Acids
Glycine, Alanine
Amino
acids
Pyruvate
Aspartate
Aspargine
Glutamate Glutamine
Amino
acids
Phenylalanin
Tyrosine
Methionine
Valine

7. Cori Cycle
Lactate
is a gluconeogenic precursor

8. Unique enzymes of gluconeogenesis are catalyzed by enzymes
Reactions 1, 2, 3 & 4
are catalyzed by enzymes
NOT used in glycolysis
GLUCOSE
1- Pyruvate to oxalacatate
by pyruvate carboxylase
2- oxalacetate to phosphoenol pyruvate
by PEP carboxykinase
3- Fructose 1,6 bisphosphate to fructose 6 phosphate
by fructose 1,6 bisphosphatase
4- Glucose 6-phosphate to glucose
by glucose 6-phosphatase
GLUCONEOGENESIS
Other reactions of gluconeogenesis are catalyzed
by same enzymes of glycolysis in the reverse direction