Learning objectives for video 2.3.

1:

Define reaction equilibrium.

Determine if a reaction is spontaneous based on the free energy of the
reaction coordinates.
Explain how a catalyst reduces the activation energy to speed the rate of a
reaction.
Understand that an enzyme stabilizes a transition state to decrease the
activation energy of a reaction.

ALAIN VIEL: Biochemical reaction, like any chemical reaction, always

proceed toward equilibrium, that is to a state where there is no net change
in the concentration of the reactants.
Now, if we look at the reaction coordinate diagram, we can easily
determine whether or not a reaction is spontaneous.
In our case, the free energy of the product is lower than the free energy of
the substrate, which means that the reaction is spontaneous, or in other
words, the change of free energy between the product and the substrate,
delta g prime naught, is negative.
And that is determined by thermodynamics parameters.
Now, external factors can also affect the equilibrium.
For example, the rate of consumption of the product in a subsequent
reaction will change the equilibrium.
Both these external factors and the thermodynamic parameters can tell us
something about the spontaneity or the directionality of the reaction but
cannot tell us anything about the speed at which the reaction proceed.
The speed of the reaction is the determined by the catalyst of the reaction.
Biological catalysts will increase the rate of the reaction by five to seven
orders of magnitude.
In most of the cases, biological catalysts that are called an enzymes are
proteins.
However, there are some cases where the enzyme is made of RNA,
ribonucleic acid.
For example, the reaction that stitch together amino acid during the
synthesis of a protein on the ribosome is catalyzed by ribosomal RNA and
not by proteins.
If we take an example of a reaction, for example, the first step of a
glycolysis, where glucose react with ATP to form glucose-6-phosphate
and ADP.
This reaction is catalyzed by an enzyme called hexokinase.
Based on the change of free energy, which is minus 16.7 kilojoules per
mole, this reaction is known to be spontaneous.
Now, imagine that we have, in a test tube, a specific concentration of
glucose and a specific concentration of ATP.
And if this reaction relies solely on the random collision between glucose
and ATP molecules, we can estimate that the rate of the reaction in this
case will be 10 to the minus 13 mole per liter per minute.
If we add to the mix, not changing the concentration of glucose and ATP, if
we add to this mix the hexokinase, then the rate of the reaction becomes
1.3 times 10 to the minus 3 moles per liter per minute.
The reaction will be 10 billion time faster in the presence of the enzyme
than in its absence.
Now, if we look again at the reaction coordinate graph, we have a
spontaneous reaction, because the free energy for the product is lower
than the free energy for the substrate.
HEATHER: Why do we need an enzyme if the reaction is spontaneous?
ALAIN VIEL: Don't be fooled by the term spontaneous.
It just mean that you have a favorable reaction that proceed from a high
free energy state to a low free energy state.
If you look at the reaction coordinate diagram, you can see that, to go from
substrate to product, you need to reach an intermediate state that has a
high free energy.
So you have an energy barrier that needs to be overcome for the reaction
to proceed, for the substrate to be converted into a product.
This activation energy is needed because there is bonds that are we are
rearranged, there are transient charge that are formed on the enzyme.
You have a distortion or change of the position of chemical groups and so
on.
So in fact, it's the amplitude of the activation energy that determine the
rate of the reaction.
The higher the activation energy is, the slower the reaction will be.
What an enzyme does, it first react with the substrate to form an enzyme-
substrate complex.
Then the substrate is converted into a product, and you have formation of
an enzyme-product complex. And finally, the product is released.
You have formation of an enzyme substrate-complex and an enzyme-
product complex as well as other intermediate of the reaction.
You have, for example, the transition state.
All of these complex, all these intermediate of the reaction, are stabilized
by the enzyme, so they have a low free energy.
And as a consequence, the activation energy in the presence of enzyme is
reduced. And when the activation energy is reduced, then the reaction will
proceed faster.
So that's how an enzyme can accelerate the reaction.