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Gluconeogenesis: The Synthesis of Glucose from Non-Carbohydrate Compounds, Study notes of Biochemistry

Explained about the What is gluconeogenesis (Definition), Location, Conversion reactions, with cycle diagrams, Importance of gluconeogenesis.

Typology: Study notes

2020/2021

Available from 01/23/2024

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Roll No: 37
GLUCONEOGENESIS
Gluconeogenesis: -
Definition:-
The Synthesis of glucose from non -carbohydrate compounds is known as
“Gluconeogenesis”.
The major su bstrate/precursor for gluconeogenesis are lactate, pyruvate, glycogenic
amino acids, propionate and glycol.
Location:-
Gluconeogenesis occurs mainly in the cytosol, although some precursors are produced
in the mitochondria.
It mostly takes place in liver (about 1kg glucose/day) and to some extent in kidney matrix
(about one-tenth of liver capacity)
Reaction of Gluconeogenesis:-
Gluconeogenesis closely resembles the reversed pathway of glycolysis, althou gh it is
not the complete reversal of glycolysis.
Essentially, 3 (out of 10) reaction of glycolysis are irreversible.
The seven reactions are common for both glycolysis and gluconeogenesis.
The Three irreversible steps of glycolysis are catalysed by the enzymes namely
hexokinase, phosphofructokinase and pyruvate kinase.
Conversion of Pyruvate to Phosphoenol pyruvate:-
This takes place in two steps. Pyruvate carboxylase is a biotin -dependent
mitochondrial en zyme that converts pyruvate to oxaloacetate in the presence of ATP
and CO2. This enzyme regulates gluconeogenesis.
Oxaloacetate is synthesized in the mitochondrial matrix. It has to be transported to the
cytosol to be used in gluconeogenesis, where the rest of the pathway occurs. Due to
membrane impermeability, oxaloacetate cannot diffuse out of the mitochondria. It is
converted to malate and then transported to the cytosol. Within the cytosol,
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Roll No: 37

GLUCONEOGENESIS

Gluconeogenesis: - Definition:- ➢ The Synthesis of glucose from non-carbohydrate compounds is known as “Gluconeogenesis”. ➢ The major substrate/precursor for gluconeogenesis are lactate, pyruvate, glycogenic amino acids, propionate and glycol. Location:- ➢ Gluconeogenesis occurs mainly in the cytosol, although some precursors are produced in the mitochondria. ➢ It mostly takes place in liver (about 1kg glucose/day) and to some extent in kidney matrix (about one-tenth of liver capacity) Reaction of Gluconeogenesis:- ➢ Gluconeogenesis closely resembles the reversed pathway of glycolysis, although it is not the complete reversal of glycolysis. ➢ Essentially, 3 (out of 10) reaction of glycolysis are irreversible. ➢ The seven reactions are common for both glycolysis and gluconeogenesis. ➢ The Three irreversible steps of glycolysis are catalysed by the enzymes namely hexokinase, phosphofructokinase and pyruvate kinase. Conversion of Pyruvate to Phosphoenol pyruvate:- ➢ This takes place in two steps. Pyruvate carboxylase is a biotin-dependent mitochondrial enzyme that converts pyruvate to oxaloacetate in the presence of ATP and CO 2. This enzyme regulates gluconeogenesis. ➢ Oxaloacetate is synthesized in the mitochondrial matrix. It has to be transported to the cytosol to be used in gluconeogenesis, where the rest of the pathway occurs. Due to membrane impermeability, oxaloacetate cannot diffuse out of the mitochondria. It is converted to malate and then transported to the cytosol. Within the cytosol,

oxaloacetate is regenerated. The reversible conversion of oxaloacetate and malate is catalysed by malate dehydrogenase, an enzyme present in both mitochondrial and cytosol. ➢ In the cytosol Phosphoenolpyruvate carboxy kinase converts oxaloacetate to phosphoenolpyruvate. Conversion of fructose 1,6-bisphosphate to fructose 6-phosphate:- ➢ Phosphoenolpyruvate undergoes the reversal of glycolysis until fructose 1,6- bisphosphate is produces. The enzyme fructose 1,6-bisphosphate converts fructose 1,6-bisphosphate to fructose 6-phosphate. Conversion of glucose 6-phosphate to glucose:- ➢ Glucose 6-phosphate catalyses the conversion of glucose 6-phosphate to glucose. The presence or absence of this enzyme in a tissue determines whether the tissue is capable of contributing glucose to the blood or not. It is mostly present in liver and kidney but absent in muscle, brain and adipose tissue.The overall summary of gluconeogenesis for the conversion of pyruvate to glucose shown: 2 Pyruvate + 4ATP + 2GTP + 2NADH + 2H++6H 2 O Glucose + 2NAD+^ + 4ADP + 2GDP

  • 6Pi + 6H+

➢ In fasting – gluconeogenesis must occur to the basal requirement of the body for glucose. ➢ Metabolites produced in tissues, accumulate in blood, eg:- lactate, glycerol, propionate etc. Gluconeogenesis clears them from blood.