GLUCONEOGENESIS

 

GLUCONEOGENESIS

Introduction:

            The production of glucose from non-carbohydrate compound is known as gluconeogenesis. It is the metabolic pathway, our body uses to turn non-glucose sources into glucose for energy a life-saving pathway. Lactate, pyruvate, glycogenic amino acids, propionate and glycerol are the major precursor of gluconeogenesis.


Definition:

            Gluconeogenesis, also called glycogenesis, formation in living cells of glucose and other carbohydrates from other classes of compounds. These compounds include lactate and pyruvate; the compounds of the tricarboxylic acid cycle, the terminal stage in the oxidation of foodstuffs; and several amino acids.

            GNG is an acronym for the term gluconeogenesis, which can define as a metabolic pathway of synthesizing new glucose molecules from the non-glucose substrates like lactate, TCA intermediates etc. Sometimes, it also refers as “Endogenous glucose pathway” as it needs an input of energy. It is an anabolic process, where the small precursor’s molecules combine to produce a high energy product like glucose. Gluconeogenesis is an important cycle, as glucose is a “Key metabolite” to carry out all catabolic processes and to sustain life.








GLUCONEOGENESIS
GLUCONEOGENESIS






Location:

            Gluconeogenesis occur mainly in the cytosol. About 1kg of glucose is produce every day.

Importance of gluconeogenesis:

ü Glucose is very key substance for the metabolism and its continues supply is essential to the body for a variety of functions.

ü Glucose is only source that supplies energy to the Skelton muscles under anaerobic conditions.

ü Gluconeogenesis helps in clearing certain metabolites produced in the tissues, which accumulates in the blod, e.g. Lactate, glycerol propionate etc.

ü The degradation of glycogen in muscles results in the formation of lactate.

ü Breakdown of fats in adipose tissue will produce free glycerol and propionate.

ü Lactate, glycerol, propionate and some amino acids are good precursor for glucose synthesis.

ü Gluconeogenesis continuously add glucose to the blood.

ü Cori cycle is responsible for the conversion of muscles lactate to glucose in liver.

Gluconeogenesis from Glycerol:

ü On hydrolysis of fats in adipose tissue glycerol is obtained.

ü Glycerol is converted to glycerol-3-phosphate by an enzyme glycerokinase.

ü Dihydroxy actetone phosphate is formed from glycerol-3-phosphate, by an enzyme called glycerol-3-phosphate dehydrogenase.

ü Dihydroxy actetone phosphate is an intermediates of glycolysis which can be used for the glucose production.


Importance of gluconeogenesis

Importance of gluconeogenesis

          


  It is a product formed as a result of triglyceride hydrolysis in the adipose tissue and transferred to the liver via blood. Glycerol is an intermediate which can produce glucose solely in the cytosol. It enters the cycle by two sequential step:

Reaction of Gluconeogenesis:

ü Gluconeogenesis closely resembles the reversed pathway of glycolysis.

ü In glycolysis all the reactions, except three are reversible these includes;

§  Pyruvate Carboxylase

§  Fructose-1,6-bisphosphate to Fructose-6-phosphate

§  Glucose-6-phosphate to Glucose

Step-1:       Pyruvate Carboxylase:

ü   Pyruvate carboxylase is a biotin dependent mitochondrial enzymes that converts pyruvate to oxaloacetate in presence of ATP and CO2.

ü  Oxaloacetate is synthesized in the mitochondrial matrix. It has to be transported to the cytosol to be used in the gluconeogenesis.

ü  Due to membrane impermeability, oxaloacetate cannot diffuse out of mitochondria.

ü  The oxaloacetate is firstly converted into malate and then transported to the cytosol. Within the cytosol, the oxaloacetate is regenerated.

ü  Malate dehydrogenase is the enzyme helps in the reconversion of oxaloacetate.

Pyruvate Carboxylase

Pyruvate Carboxylase  



    In the cytosol, the enzyme oxaloacetate carboxykinase converts oxaloacetate to oxaloacetate.

Step-2:       Conversion of Fructose 1,6-bisphosphate to Fructose                          6-bisphosphate:

ü  Enzyme Fructose 1,6-bisphosphatase converts Fructose 1,6-bisphosphate to Fructose 6-phosphat.





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