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L03v01
[00:00:00.00]
[00:00:01.78] PROFESSOR: Hi. In this set of lectures we'll talk about cell energetics and
enzyme catalysis. We'll show that basic thermodynamic considerations apply equally well to life
as it does to all phenomenon. We'll talk about chemical reactions, and how free energy controls
their direction, and the relative amounts of products at equilibrium. We'll talk about activation
energies controlling reaction kinetics. We'll talk about how the cell manages to perform
energetically unfavorable reactions by coupling them to energetic equally favorable ones, such as
ATP hydrolysis.
[00:00:38.53] The simplest view of energetics of cells is this, we consume food and we produce
two things, energy and building block materials. Then we can combine these building blocks into
some of the desired molecular products using some of the energy we captured. The exception to
this would be plants or bacteria that instead of ingesting food, photosynthesize, and produce
sugars using sunlight and carbon dioxide.
[00:01:08.42] Cells do not violate the second law of thermodynamics, which states that the
entropy of the system always increases. At one point, historically, there was some confusion
about this because cells are so obviously highly ordered. And this was originally seen as a
contradiction. However, the answer to this situation is that you have to consider the entire
system. Living cells create order within their membrane confines, but the process creates more
than sufficient disorder in the environment by the bacteria giving up heat, thus the entropy of the
total system increases. So there's no contradiction between life and the second law.
[00:01:51.08] The property that determines whether reactions occur spontaneously is the change
in the Gibbs free energy. On this slide, we see that the free energy of this reaction would be the
difference between B and C. Because of the law of microscopic reversibility, most of the Y
reactant will convert to the X product, while a smaller amount of the X product will convert back
to the Y reactant. Because there's always an equilibrium between the two species, the ratio of the
reactants and products are determined by the change in free energy, and also by the ratio of the
forward and reverse reaction rates.
[00:02:29.12] The forward reaction rate is much faster because the activation energy for the
forward reaction is the difference between A and B. Whereas the action activation energy for the
reverse reaction, is the difference between A and C, a much larger number. Since this is such a
large activation energy, not many molecules make it over the barrier within a given time period.
[00:02:54.66] When enzymes or other catalysts speed reactions, they do so by reducing the
activation energy from A to B to a smaller value, which is shown here as D to B. Now this
activation energy is smaller, and Y can go even faster to the product X. The reverse reaction also
speeds up, but again, the relative ratios have a relationship governed by their free energy
differences.
[00:03:20.83] Notice that in both the uncatalyzed case and the catalyzed case, the energy of the
reactants and the energy of the products does not change. You've not changed the direction of the
reaction. You've not changed the relative amounts of the products and reactants when you're in
equilibrium. All that you've changed is the rate at which you approach equilibrium.
[00:03:45.83] And here I've put in some numbers just for the purpose of discussing that the free
energy of the reaction is -15 kilocals per mole, starting with the reactant Y at energy b, and
proceeding down to product X at energy c. And that's the direction of a spontaneous reaction. It
will always be specified by a negative Gibbs free energy change.
[00:04:09.03] And here we schematize the amounts at equilibrium, smaller amounts of Y, larger
amounts of X. Faster rates of conversion from Y to X, and slower rates of conversion from X to
Y.
[00:04:24.83] When considering energy changes for two reactions, you can simply add the delta
G values of the individual steps to determine the overall change, and how the overall reaction
will proceed. In this case, we have X turning to Y. This is an unfavorable reaction because it has
a positive delta G difference of 5 kilocalories per mole. But when Y gets converted to Z, this is a
very energetically favorable reaction with a negative delta G of 13 kilocalories per mole. The
combined conversion of X to Z is energetically favorable at minus 8 kilocalories per mole. So
even though the initial step is unfavorable, we're still allowed to have this overall reaction
sequence go because it is energetically favorable in some. We'll see these two processes draw out
in terms of molecules in the next slide.
[00:05:20.03] So now we see that X going to Y is unfavorable, so there's more of X, and less of
Y. But going from Y to Z is very favorable. So there's much more of Z. But over time, we've got
net conversion of X to Z, because this is the most thermodynamically stable molecule. You can
think of Y as a branching point. Every time an X molecule goes to Y, the molecule at Y can go
either to X or Z, with Zs being sort of a sink, so that the unfavorable equilibrium between X and
Y over time will get siphoned off into molecule Z.
[00:05:59.11] In general, we'll see that unfavorable reactions, even if they're not sequential, can
be coupled to other reactions like the hydrolysis of ATP. Because ATP hydrolysis is so
energetically favorable, then you can actually make molecules like Y, which are less stable, less
thermodynamically stable than molecule X. But you're paying for it by the hydrolysis of ATP.
And we'll see some examples of that.
[00:06:26.57] Now the catalysis-- the lowering of activation energy-- does not change the
equilibrium. So that is made painfully obvious in this slide here, by showing you that the
uncatalyzed, or the enzyme catalyzed reaction, of the same amount of X molecules and the same
amount of Y molecules. The thing that's different is the rates of achieving it. Here's one arrow in
each direction, which means slow. Many arrows symbolizes that the reaction proceeds more
rapidly.
[00:06:56.70] This slide recapitulates what we saw on the original slide, but highlights the role of
the activated carrier molecule. We consume food and break it down capturing energy in the
forms of activated carrier molecules, the most important of which is a ATP. And we use then the
ATP energy to do energetically unfavorable reactions, building up the parts of the cell that we
need for growth.
[00:07:23.24] Here's a molecule of ATP which we've seen before. And just to reiterate why it's
such a high energy molecule, we know that from our electrostatic rule that like charges repel.
And we've got four negative charges confined to a small molecular space here. If we're able to
cleave that from ATP, adenosine triphosphate, to ATP, adenosine diphosphate, plus an inorganic
phosphate, then we've relieved some of the electrostatic repulsion. And so this configuration is a
much lower energy state.
[00:08:00.82] In addition to ATP, NADH and NADPH, are important high energy, intermediate
molecules. They participate in the synthesis of ATP in itself. And also in the synthesis of many
molecules, by providing high energy electrons to reduce a molecule to a higher state. We'll talk
about these molecules a lot more in the second part of the course. For this portion of the course,
it's going to be primarily ATP that we're concerned about.
[00:08:31.98] I'd like to leave with two examples of how ATP is used to drive the synthesis of
bio-polymers. In this case, we have two amino acids being joined to elongate a protein. We have
an amino acid here, an amino acid here. And here is the new peptide bond. That is driven by the
coupling of the MIO end of one new amino acid to the carboxyl end of the existing polypeptide
chain. You lose a water molecule in a condensation reaction, and you're creating a new peptide
that's one amino acid longer. On its own, this reaction is energetically unfavorable. But it is paid
for by the concurrent utilization of a molecule of ATP.
[00:09:19.07] Similarly, we have nucleic acid synthesis. In this case, RNA is growing in the five
prime to three prime direction. Once again, you have a loss of water in a condensation reaction
of the next nucleotide, driven by the hydrolysis of phosphate groups.
[00:09:37.36] OK, thank you very much for listening. In this video, the important points we
covered were that thermodynamics applies to life as it does to all physical phenomena, that free
energy changes determine the direction of spontaneous reactions, that activation energies
influence reaction kinetics, but not equilibrium ratios, and that energetically unfavorable
reactions are powered by coupling them to energetically favorable ones. Thanks for listening.