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Transcript of GLUCONEOGENESIS
It is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, pyruvate, glycerol, and glucogenic amino acids.
In animals, gluconeogenesis takes place
mainly in the liver and, to a lesser extent,
in the cortex of kidneys.
This process occurs during periods of
fasting, starvation, low-carbohydrate diets,
or intense exercise and is highly endergonic.
The process of gluconeogenesis helps keep blood glucose levels within critical limits.
It is stimulated by cortisol and other glucocorticoids and by the thyroid hormone thyroxine. Formerly called glyconeogenesis.
The reverse anabolic process of Gluconeogenesis is equally important as the breakdown and extraction of energy from glucose that happens during the catabolic process of Glycolysis.
The major inputs come from the breakdown of amino acids and from lactate produced by the muscle tissue and transported to the liver by the bloodstream.
It is important to note that the formation of Acetyl CoA from pyruvate, catalyzed by the pyruvate dehydrogenase complex, is not reversible. The energy required for the reverse reaction is too great.
The seemingly simple process of converting pyruvate to
phosphoenolpyruvate involves several steps, some in the
matrix of the mitochondria and others in the cytoplasm.
The first step in the gluconeogenesis pathway involves the
conversion of the 3-carbon pyruvate to the 4-carbon intermediate
oxaloacetate. This energy-requiring step is catalyzed by pyruvate
carboxylase, an enzyme that requires biotin as a cofactor.
Oxaloacetate cannot get out of the
mitochondria directly but first has to
be converted to MALATE by the same
malate dehydrogenase used in the TCA
Once in the cytoplasm, the malate is reconverted
to oxaloacetate, this time by a cytoplasmic form
of malate dehydrogenase.
The second unique enzyme of gluconeogenesis, phosphoenolpyruvate (PEP) carboxynase, catalyses the conversion of oxaloacetate to phosphoenolpyruvate.
Note that this is another energy requiring step.
The conversion of pyruvate to PEP requires energy input (GTP+ATP) and carboxylation and decarboxylation steps.
Gluconeogenesis proceeds by simple reversal of the
steps of glycolysis (using the same enzymes) up to
At this point, reversal of the highly exergonic
phosphofructokinase step of glycolysis is avoided
by a simple phosphate cleavage.
Fructose-6-biphosphate is then converted to
glucose-6-phosphate by the phosphoglucose
isomerase ( a glycolysis enzyme working in reverse).
Then all that remains is to remove one phosphate
group to generate glucose.
The overall process of Gluconeogenesis is energy intensive:
2 Pyruvate + 4 ATP + 2 GTP + 2 NADH + 2H + 6 H2O
Glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD
Compare this with Glycolysis:
Glucose + 2 ADP + 2 Pi + 2 NAD
2 Pyruvate + 2 ATP + 2 NADH + 2H + 2 H2O