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Introduction of Glucose Metabolism
Lecture-4
GLUCONEOGENESIS
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
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
Precursors
of
Gluconeogenesis
Oxalacetate
Intermediate of
CITRIC ACID CYCLE
GLUCOSE
Triacylglycerol
in adipose tissue
Fatty acids
Gluconeogenesis
Glycerol
Pyruvate
Lactate
Glucogenic amino acids
in proteins as sk. ms.
Glycerol as a
gluconeogenic Substrate
Glycerol
Glycerol
Kinase
ATP
Glycerol 3-phosphate
ADP
NAD+
Glycerol 3-phosphate
dehydrogenase
Glucose
NADH
Dihydroxyacetone phosphate
GK: Glycerol kinase only in liver & kidneys
Glucogenic
Amino Acids
Pyruvate
Aspartate
Aspargine
Phenylalanin
Tyrosine
Amino
acids
Amino
acids
Glycine,
Alanine
Glutamate
Glutamine
Methionine
Valine
Cori Cycle
Lactate
is a gluconeogenic precursor
Unique enzymes of gluconeogenesis
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
Other reactions of gluconeogenesis are catalyzed
by same enzymes of glycolysis in the reverse direction
GLUCONEOGENESIS