To obtain energy, the body uses food or it’s own reserves.
The main sources of energy are sugars and fats.
This Chalk Talk episode looks at how the breakdown of sugar yields energy in the form of ATP.
The process responsible is glycolysis.
Its name already pretty much gives it away: In this metabolic process, glucose, whose
name is derived from the Greek word “glykys” meaning sweet, is gradually “lysed”, that
is, degraded.
Glycolysis occurs in the cytosol of cells and yields pyruvate as the end product.
Pyruvate is converted to acetyl-CoA, and can enter the citric acid cycle.
If we look at glycolysis from a chemical perspective, it’s the cleavage of a C6 unit into two
C3 units.
This process comprises 10 steps.
Now, let’s take a closer look at the reactions involved.
If you’d not only like to see the names of the substances but also the molecular structures,
then click on Dieter’s red molecule.
You can hide these structures at any time by clicking on the molecule again.
So let’s get started:
In the first reaction, glucose is converted into glucose-6-phosphate.
This reaction activates glucose.
In other words, glucose now contains an energy-rich bond, just like ATP, which was shown in the
previous Chalk Talk episode.
The phosphorylated glucose can no longer exit the cell because there are no transporters
available.
This reaction also helps maintain a low amount of intracellular glucose, which facilitates
further glucose uptake by the cell.
The phosphate required for this reaction stems from ATP.
So, in the beginning, glycolysis consumes energy, despite it being a process that provides
energy.
At first, this results in a negative energy balance.
The enzyme catalyzing the first reaction step is hexokinase.
Hexokinase is one of three key enzymes involved in glycolysis, that is, it’s an irreversibly
acting enzyme.
Its activity can decisively regulate the glycolytic pathway.
We’ll take a closer look at the regulation processes in part 3 of our course on energy
metabolism.
In the next step, the six-membered ring is converted to a five-membered ring, that is,
glucose-6-phosphate is converted to fructose-6-phosphate.
The enzyme catalyzing this reaction is glucose-6-phosphate isomerase.
In step 3, sugar is phosphorylated a second time using an additional ATP molecule, resulting
in fructose 1,6-bisphosphate.
This further reduces the energy balance of glycolysis to a total negative balance of
2 ATP molecules.
The enzyme catalyzing this reaction is phosphofructokinase 1.
It’s also an important key enzyme of glycolysis.
Because the conversion reaction to fructose 1,6-bisphosphate is the slowest in the entire
glycolysis process, it’s the rate-limiting step of glycolysis.
In the fourth step of glycolysis, the C6 unit is cleaved into two C3 units by the enzyme
aldolase.
Because the starting material for cleavage, fructose 1,6-bisphosphate, is not symmetrical,
the C3 compounds formed are different.
They are glyceraldehyde-3-phosphate, in short GAP, and dihydroxyacetone phosphate, in short
DHAP.
These two isomers can be readily interconverted and are present in almost equal quantities.
However, only GAP can be further metabolized in glycolysis.
Therefore, the DHAP formed is converted into GAP by the enzyme triose phosphate isomerase.
This way, two molecules of GAP are formed from one molecule of glucose.
Up until this stage, all reactions were important for cleaving glucose.
The following reactions facilitate the transformation of both C3 units to pyruvate.
GAP is initially converted to 1,3-bisphosphoglycerate.
The reaction is catalyzed by GAP dehydrogenase, resulting in one reducing equivalent of NADH
and H+.
This means that each NADH and H+ has the potential to carry out one reduction reaction, like
reducing a ketone to an alcohol.
To do so, it needs to transfer two electrons and protons.
Now, NADH and H+ can be used to create ATP by the electron transport chain, which will
be further discussed in episode 7 of the course.
For now, let’s just add it to our energy balance.
Two molecules of GAP are formed from one molecule of glucose, producing a total of two reducing
equivalents of NADH and H+.
There’s another important aspect for the energy balance: The phosphate group transferred
to GAP does not stem from ATP but from the cell’s phosphate stores.
Therefore, no energy is consumed in this reaction.
In contrast, this phosphate group can be later transferred to ADP during the seventh and
reversible step of glycolysis.
Therefore, the reaction provides energy.
So, from each glucose molecule, two molecules of 1,3-bisphosphoglycerate are formed, with
the reaction, therefore, yielding two molecules of ATP per glucose molecule.
With this, the balance of ATP is leveled.
The energy required for forming ATP is obtained when phosphate is cleaved from the molecule,
breaking an energy-rich bond.
Such a transfer of phosphate from an energy-rich metabolic intermediate to ADP is termed substrate-level
phosphorylation.
Let’s go back to the glycolysis process: In the seventh step, 3-Phosphoglycerate is
formed.
The enzyme catalyzing this reaction is correspondingly termed phosphoglycerate kinase.
In the eighth reaction step, the remaining phosphate group in the molecule is shifted,
forming 2-phosphoglycerate.
The enzyme involved is termed phosphoglycerate mutase.
Subsequently, water is cleaved from 2-phosphoglycerate by the enzyme enolase in the ninth step of
glycolysis.
The resulting phosphoenolpyruvate is an unstable molecule and can transfer its phosphate group
more easily than 2-phosphoglycerate.
This transfer takes place in the tenth and final step of glycolysis, in which phosphoenolpyruvate
is converted into pyruvate.
The enzyme responsible for this reaction is pyruvate kinase.
Again, this reaction transfers the phosphate group to ADP, forming ATP.
So, the final step of glycolysis yields an additional two molecules of ATP per molecule
of glucose.
Now, what does this mean for the overall balance of energy of glycolysis?
Each molecule of glucose yields two ATP and two NADH and H+.
Because the final phosphate group transfer is an irreversible reaction, pyruvate kinase
is also a key enzyme of glycolysis.
Back to pyruvate again.
Following glycolysis, pyruvate dehydrogenase converts pyruvate to acetyl-CoA.
During this irreversible reaction, one molecule of CO2 and one NADH and H+ reducing equivalent
are formed.
For glucose to be completely oxidized to carbon dioxide, acetyl-CoA is passed on to the citric
acid cycle.
Alternatively, it can also be used as a building block in other metabolic processes, such as
fatty acid synthesis.
Now, let’s finish off by summarizing the five most important aspects of the reactions
involved in glycolysis:
Glycolysis occurs in the cytosol of all cells in the body.
A C6 unit of glucose is cleaved into two C3 units of pyruvate.
Glycolysis occurs in 10 reaction steps.
After initially consuming two molecules of ATP, the metabolism produces four molecules
of ATP and two equivalents of NADH and H+.
Overall, glycolysis produces two ATP and two NADH and H+.
The three key enzymes of glycolysis are hexokinase in step 1, phosphofructokinase 1 in step 3,
and pyruvate kinase in step 10.
Would you like to know how these reaction steps are regulated and adjusted to the body’s
energy needs?
Then stay tuned for the next episode in our biochemistry course.
But first, we’ve prepared a quiz for you.