Biochemistry
Lec. 6
Monosaccharides Metabolism
and Gluconeogensis
Dr. Mohammed Ayad
M.B.Ch.B.
C₆H₁₂O₆
Fructose catabolism
• The 1st step of
catabolism involves
phosphorylation of the
sugar at the 1-carbon by
fructokinase to product
fructose-1-phosphate.
Fructose catabolism
• The resulting fructose1-phosphate is then
split to form
dihydroxyacetone
phosphate and
glyceraldehyde.
• Glyceraldehyde is
convert to
glyceraldehyde-3phosphate by
triokinase.
Fructose catabolism
• Both halves of
fructose
(dihydroxyacetone
phosphate and
glyceraldehyde-3
phosphate) enter
the glycolytic
pathway as triose
phosphates.
Galactose catabolism
• The 1st step of
catabolism involves
phosphorylation of the
sugar at the 1-carbon by
Galactokinase to
product: galactose-1phosphate.
Galactose catabolism
• Galactose-1-phosphate regenerates a
nucleotide derivative of glucose: uridine
diphosphate glucose (UDP-glucose) to
product: UDP-galactose by: galactose-1phosphate uridyltransferase to transfer
of the uridine nucleotide group.
• UDP-glucose serve as a substrate for
glycogen synthesis, or, be converted to
glucose-1-phosphate. The latter may be
isomerized to glucose 6-phosphate and
thus enter glycolysis.
Galactose catabolism
UDP- galactose is then
convert to UDP- glucose
through the action of an
epimerase.
Gluconeogenesis
• Some tissues, such as the brain, red blood cells, kidney medulla, lens and
cornea of the eye, testes, and exercising muscle, require a continuous
supply of glucose as a metabolic fuel.
• Liver glycogen, an essential postprandial source of glucose, can meet
these needs for only ten to eighteen hours in the absence of dietary
intake of carbohydrate.
• During a prolonged fast, however, hepatic glycogen stores are depleted,
and glucose is by a reversal of glycolysis, it was not simply, because the
overall equilibrium of glycolysis strongly favors pyruvate formation.
• Instead, glucose is synthesized by a special pathway, gluconeogenesis,
that requires both mitochondrial and cytosolic enzymes.
• Definition: It is the process by which glucose
molecules are produced from non
carbohydrate precursors like Lactate,
glucogenic amino acids, or glycerol.
• Gluconeogenesis occurs mainly in the liver,
and to a lesser extent in the renal cortex.
• The pathway is partly mitochondrial and partly
cytoplasmic.
Three Irreversible reactions in
glycolysis catalyzed by:
①- Hexokinase.
②- Phosphofructokinase.
③- Pyruvate kinase.
•
Pyruvate & Phosphoenolpyruvate: ❶Reversal of the reaction catalyzed by
pyruvate kinase in glycolysis involves two
endothermic reactions.
•
Mitochondrial pyruvate carboxylase
catalyzes the carboxylation of pyruvate to
oxaloacetate, an ATP-requiring reaction in
which the vitamine biotin is the coenzyme.
Biotin binds CO2 from bicarbonate as
carboxybiotin prior to the addition of the
CO2 to pyruvate.
•
A second enzyme, in cytosol -❷
phosphoenolpyruvate carboxykinase,
catalyzed the decarboxylation and
phosphorylation of oxaloacetate to
phosphoenolpyruvate using GTP as the
phosphate donor.
Fructose 1,6-Bisphosphate & Fructose 6-Phosphate:
• The conversion of fructose 1,6-bisphosphate to
fructose -6-phosphate ❸, for the reversal of
glycolysis, is catalyzed by fructose 1,6-bisphosphatase.
• It is present in the liver, kidney, and skeletal muscle,
but is probably absent from heart and smooth muscle.
Glucose 6-phosphate & Glucose:
• ❹ - The conversation of glucose 6-phosphate to
glucose is catalyzed by glucose 6-phosphatase.
• It is present in the liver and kidney, but absent
from muscle and adipose tissue.
Key Gluconeogenic Enzymes
1.
2.
3.
4.
Pyruvate carboxylase
Phosphoenol pyruvate carboxy kinase
Fructose 1 6 bisphosphatase
Glucose 6 phosphatase
Lactate to Pyruvate
Glycerol to DHAP
Regulation of
Gluconeogenesis and
Glycolysis in the Liver