BIOL2171 Lecture Notes - Lecture 4: Dihydroxyacetone Phosphate, Phosphoenolpyruvic Acid, Citric Acid Cycle

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15 Jun 2018
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Topic 4: Glycolysis Overview
Glycolysis is one of the principal pathways generating ATP in cells and is present in all cell
types in the human body.
The central role of glycolysis is related to the availability of glucose as a fuel in blood and to its
ability to generate ATP in the presence and absence of oxygen.
Glycolysis can lead to the generation of pyruvate, which is subsequently oxidized in the TCA-
cycle or to the generation of lactate, which is released from the cell.
The principle energy containing products of glycolysis are ATP and NADH
NADH can only be used to generate energy in the presence of oxygen
As a result, NADH is only produced under aerobic conditions, but not in the absence of oxygen,
where it is used to reduce pyruvate to lactate.
Glycolysis is not the only pathway to use glucose in the body. Glucose can be oxidized in
the pentose-phosphate pathway, which is important for the generation of NADPH or it can be
stored by forming glycogen. After a meal glucose is the main fuel for many cells in the body.
Glycolysis can be divided in two phases: preparation phase and the ATP-generating phase
o In the first reaction of the glycolytic pathway, glucose is phosphorylated to glucose-6-
phosphate
This is done by a phosphate group being transferred from ATP to glucose, making
glucose-6-phosphate
Glucose-6-phosphate is more reactive than glucose, and the addition of the
phosphate also traps glucose inside the cell since glucose with a phosphate can't
really cross the membrane
o Glucose is also isomerized to fructose-6-phoshate
Glucose-6-phosphate is converted into its isomer, fructose-6-phosphate
o Fructose-6-phosphate is phosphorylated again to form Fructose-1,6-biphospahte
A phosphate group is transferred from ATP to fructose-6-phosphate, producing
fructose-1,6-biphosphate
This step is catalysed by the enzyme phosphofructokinase, which can be regulated
to speed up or slow down the glycolysis pathway
o This molecule is then split by aldolase into glceraldehyde-3-
phosphate and dihydroxyacetone phosphate
Fructose-1,6-biphosphate splits to form 2 three-carbon sugars, dihydroxyactone
phosphate (DHAP) and glyceraldehyde-3-phosphate
They are isomers of each other, but only one - glyceraldhyde-3-phosphate- can
directly continue in glycolysis
DHAP is converted into glyceraldehyde-3- phosphate
These two molecules are interconvertible
o Glyceraldehyde-3-phosphate is then oxidised and phosphorylated to form 1,3-bis-
phospho-glycerate.
Two half reaction occur together
Glyceraldehyde-3-phosphate is oxidised
NAD+ is reduced to NADH and H+
The overall reaction is exergonic, releasing energy that is then used to
phosphorylate the molecule, forming 1,3-bis-glycerate
o ATP is produced in the next step, when it is converted to 3-phosphoglycerate
1,3-bis-phosphoglycerate donates one of its phosphate groups to ADP, making a
molecule of ATP and turning into 3-phosphoglycerate in the process
o This molecule is isomerized into 2-phosphoglycerate
3-phosphoglycerate is converted into its isomer, 2-phosphoglycerate
o Removal of water generates phosphoenolpyruvate
It loses water and becomes phosphoenolpyruvate (PEP)
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