Post on 07-May-2015
GLUCONEOGENESIS
Gluconeogenesis
the synthesis of glucose from noncarbohydrate molecules
Noncarbohydrate:lactate, pyruvate, glycerol, and certain α-keto acids (molecules derived from amino acids).
Where occur in ?
primarily in the liver. In certain situations (i.e., metabolic acidosis or
starvation) the kidney can make new glucose. Very little in brain or muscle
The pathway
The reaction sequence in gluconeogenesis is largely the reverse of glycolysis.
three glycolytic reactions (the reactions catalyzed by hexokinase, PFK-1, and pyruvate kinase) are irreversible.
In gluconeogenesis, alternate reactions catalyzed by different enzymes are used to bypass these obstacles.
1. Synthesis of PEP( in mitochondrial matrix)
2. Conversion of fructose-l,6-bisphosphate to fructose-6-phosphate.
(in cytosol)
3. Formation of glucose from glucose-6-phosphate. (in smooth endoplasmic reticulum)
Glucose-6-phosphatase, found only in liver and kidney, catalyzes the irreversible hydrolysis of glucoses-phosphate to form glucose and Pi. Glucose is subsequently released in to the blood.
Precursors for Gluconeogenesis
pyruvate Lactate Glycogenic amino acid Glycerol Citric acid cycle intermediates
pyruvate
lactate dehydrogenase(LDH)
NADH + H+ NAD+
lactate
Lactate
Glycerol
Glycerol 3-phosphate can be oxidized in reactions catalyzed by either of two dehydrogenases; both reactions yield reduced coenzymes.
The liver contains both dehydrogenases, so both reactions can occur there.
Energy used Two pyruvate molecules are required to
synthesize one molecule of glucose.
Energy is required at the following steps.
Pyruvate carboxylase 1ATP(×2)=2ATP
PEP carboxykinase 1GTP(×2)=2ATP
Phospholglycerate kinase 1ATP(×2)=2ATP
ATP ADP
Phospholglycerate kinase
total=2+2+2=6ATP
Transport of oxaloacetata
Exit the mitochondrion
malic acid
malic acid Oxaloacetate
Oxaloacetate
Pyruvate
Pyruvate
Oxaloacetate
pyruvate carboxylase
ATP + CO2
ADP + Pi
malic acid
NADH + H+
NAD+
malic acidOxaloacetate
PEP
Phosphoenol pyruvate carboxkinase
GTP
GDP + CO2
Mt
Cytosol
malate dehydrogenase
Reciprocal regulation of glycolysis and gluconeogenesis Substrate cycle (Futile cycle)
A pair of opposing, metabolically irreversible reactions that catalyzes a cycle between two pathway intermediates. Substrate cycles provide sensitive regulatory sites.
The Cori cycle
An interorgan metabolic loop that recycles
carbon and transports energy from the liver to
the peripheral tissues. Glucose is released from
the liver and metabolized to produce ATP in
other tissues. The resulting lactate is then
returned to the liver for conversion back to
glucose by gluconeogenesis.
The Cori cycle
The significance of gluconeogenesis
1.To keep blood sugar level stable Gluconeogenesis meets the demands of the body for glucosewhen carbohydrate is not available in sufficient amount from the diet. More than 25% of glucose is supplied by gluconeogenesis.
2.To replenish liver glycogen
3.To regulate acid-base balance