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L11v01a_oxy_phos_part_1
[00:00:00.00]
[00:00:00.86] Hi. In this video, we'll talk about oxidative phosphorylation, which is the main
method that cells use to make the majority of their ATP. We'll talk about the mechanism that
ATP is made, which involves the coupled vectorial processes of electron transport, establishment
of a proton gradient, and the use of that proton gradient to drive ATP synthesis.
[00:00:27.20] And finally in this video, we'll look in detail at the structure of the mitochondrial
inner membrane, which is the location for most of these processes, as it is the essential barrier
between the inner mitochondrial matrix and the mitochondrial inter-membrance space.
[00:00:46.41] Now, in our prior lectures, we saw the process of glycolysis, where cells took
glucose and other carbohydrates and managed to obtain a small amount of ATP using substratelevel phosphorylation in an oxygen-independent manner. Today, we're going to talk about the
much more efficient mechanism of generating ATP which utilizes oxygen, and that involves
capturing high-energy electrons in the carrier molecules of NADH and FADH2, which then
shuttles the electrons to the electron transport chain.
[00:01:26.47] Just to review, in glycolysis, we took glucose, converted it to pyruvate. In the
process, we generated a net of two ATP and two NADH molecules. In the citric acid cycle, for
each rotation we generate three NADH molecules, a molecule of FADH2, and a molecule of
GTP. And we do that twice because glucose produces two molecules of pyruvate. We'll see a
more detailed accounting in future slides.
[00:01:57.49] And this is just a reminder that both glycolysis and sugars will create pyruvate,
which will funnel into Acetyl CoA. And fatty acids that are imported into the cell get transported
to the mitochondrial matrix, undergo beta-oxidation, and produce two carbon units of Acetyl
CoA as well, allowing both Acetyl CoA types of molecules to enter into the citric acid cycle.
[00:02:27.23] Today's lecture will focus specifically on the process of NADH, donating highenergy electrons to an electron transport chain, which will drive the formation of a proton
gradient, which is then used to drive the synthesis of ATP, and the electrons will eventually get
dumped onto oxygen, forming water as a byproduct.
[00:02:53.46] In addition to talking about oxidative phosphorylation, or the process of respiration
that animals employ, we'll also, in later lectures, look at photosynthesis, which is the mechanism
whereby plants and photosynthetic bacteria and algae produce ATP. The two processes share a
lot of features, which are highlighted in this slide.
[00:03:20.69] Both utilize high-energy electrons. In photosynthesis, the electrons get their high
energy from the absorption of a photon, the energy that's present in sunlight. And in foodstuffs,
it's from energy-rich molecules such as carbohydrates.
[00:03:39.55] In both cases, the high-energy electrons are used to pump protons across an inner
membrane, creating an electrochemical gradient of protons, which can then be used primarily to
drive ATP synthesis, but can be used for other processes in some organisms as well.
[00:04:00.47] The term chemiosmotic-coupled processes denotes the fact that electrochemical
gradients across a membrane are going to be used to drive a particular chemical event, which, in
this case, is the synthesis of ATP. And here, we start to see some details of chemiosmotic
coupling.
[00:04:23.85] High-energy electrons will be donated to a protein. The fact that the protein now
has an additional negative charge will change the conformation of the protein. This
conformational change will result in pumping protons from the inner mitochondrial matrix to the
inner membrane space. This creates an excess of protons here, relative to the inside of the
membrane.
[00:04:51.68] And then after the proton pumping has occurred, that will again change the
conformation of the protein. Now the affinity for that electron is decreased, and this electron will
be passed on to another electron acceptor, whether it be protein or small molecule.
[00:05:08.94] Now, in the second stage, we use the excess protons that are available in the inner
membrane space. They will diffuse down their electrochemical gradient in an energetically
favorable direction, and that energy will be captured partially by the synthesis or the coupling of
inorganic phosphate in ADP into the energy currency of the cell, which is the molecule ATP.
This process of osmosis and chemistry forms the fundamental basics of chemiosmotic coupling.
[00:05:47.36] Now on this slide, we start to schematize some of the events of oxidative
phosphorylation. As we know, acetyl CoA that's produced from fats and other high-energy
molecules enters into the citric acid cycle. The carbon atoms of acetyl CoA will finally get
excreted as carbon dioxide, which is as oxidized as a carbon can get in life forms, and there's no
more extractable energy from that.
[00:06:16.86] As it's being oxidized, high-energy electrons are being captured on NADH, which
then will diffuse over to the inner mitochondrial membrane and donate those two high-energy
electrons to a series of one, two, three different protein complexes that all reside within the inner
mitochondrial membrane.
[00:06:40.16] Now, these are schematized here to suggest that these are the highest-energy
electrons, these are medium-energy electrons, and these are lower-energy electrons. Each time an
electron is placed on this protein complex, it will pump hydrogen ions, or protons, that's
synonymous, from the inner mitochondrial matrix to the inter-membranous space out here. After
doing that, the electrons will get transferred from this protein complex to this protein complex,
which will again pump protons, and again at a third protein complex.
[00:07:21.33] At this point, the electrons are of low enough energy that they can no longer
sufficiently drive a proton that's being pumped, and so they are dumped onto molecular oxygen
that we breathe. And it's going to pick up some protons from the internal milieu, and the
electrons plus oxygen plus protons will form water as a byproduct. And again, this is exactly
what happens when you burn hydrocarbons. You produce carbon dioxide and water.
[00:07:55.59] On this slide, it's just a reminder of how NADH carries these high-energy
electrons as part of a hydride ion, which then, when it approaches the protein complex, will
donate two electrons to the electron transport chain, a proton to the internal milieu, and this will
reform NAD+, which is the acceptor molecule for the electrons in the citric acid cycle.
[00:08:28.43] This is, once again, the electron micrograph of the mitochondria, which we saw in
the first class. Just as a reminder, there are two membranes to this organelle. There's the outer
membrane and the inner membrane, which folds in here.
[00:08:43.89] And so there's two spaces. There's the inner mitochondrial matrix, which is the
bulk of the volume here. And then there's a small space between the outer and inner membrane
called the inner membrane space, and this is the location to which protons will get pumped and
will achieve high concentrations in this small space.
[00:09:06.29] The proteins in the inner mitochondrial membrane will now be pumping protons
from the inner mitochondrial matrix into this inner membranous space, the small space. And so
even a small number of protons will greatly increase the concentration. And then the protons, the
excess protons in this space, will then be transported back out into the mitochondrial matrix,
driving the synthesis of ATP.
[00:09:34.15] So one of the key advantages of having these two membranes is the creation of
two separate compartments, the inner mitochondrial matrix and the inner membranous space in
which different chemistries can occur, different concentrations of molecules can be maintained,
and the differences can be used to drive important processes.
[00:09:54.00] And this is a good place to stop. We'll resume this video with a discussion on the
events happening at the inner mitochondrial membrane. Thanks for listening.