Biochemistry Citric Acid Cycle I

Hello and welcome back to Educator.com, and welcome back to Biochemistry.0000

We just finished discussing glycolysis, gluconeogenesis and the pentose phosphate pathway.0004

Now, we are going to continue on with our metabolic pathways, and we are going to start discussing the citric acid cycle.0010

Let's just jump right on in.0020

OK, I am going to go ahead and do just a quick overview, again, of the stages of cellular respiration, so that we have an idea of where it is that we are in the big picture; and then, we will actually start to get into the citric acid cycle and the conversion of the pyruvate that was formed during glycolysis into acetyl-CoA, and then, of course, in the next lesson, we will go ahead and start the citric acid cycle.0024

OK, the stages of cellular respiration, let's see, and what we mean by that is just the conversion of glycolysis to pyruvate ultimately to acetyl-CoA , the citric acid cycle all the way down; and we produce the CO₂, and we reduce oxygen via all those electrons that we took away from all of these oxidative steps.0045

Let's see here; we started with glucose.0080

That was our first step; from glucose, the glycolysis, we went to pyruvate.0083

We have already taken care of this first step; that was the glycolysis, the pyruvate, acetyl coenzyme A.0091

Now, from here, the acetyl-CoA actually enters the citric acid cycle.0103

OK, and over here, later on, when we actually discuss fatty acid catabolism and amino acid catabolism, the breakdown of those things, they also end up funneling into acetyl-CoA and entering the citric acid cycle.0115

So, I will just go ahead and draw that this way, OK, something like that.0132

OK, now, let me go ahead and put over here NADH and FADH₂.0141

I will go ahead and put a little rectangle around that, and then, over here, I will go ahead and put the electron transport chain.0151

The final step in cellular respiration, what oxidative phosphorylation...it is going to be our final culminating step of this thing called cellular respiration- the ultimate breakdown of the things that we ingest, whether it is fatty acids, amino acids and carbohydrates, so, amino acids, electron transport chain, and let me go ahead and put a little square around that.0165

Here, in the electron transport chain, what happens is this thing called oxidative phosphorylation, different from what we talked about earlier when we talked about glycolysis...remember we talked about the formation of ATP?0193

That was substrate level phosphorylation; this is where most of the ATP that is produced in the body is produced.0207

It is called oxidative phosphorylation, so ADP + PI is converted into ATP.0214

That is one of the major products; all of this is designed to produce ATP, so that ATP can run the body because ATP is the energy currency.0220

The other thing that happens is that oxygen gas is actually reduced to water, so H₂O, right, oxygen?0230

Normally, it has an oxidation state of 0; H₂O has an oxidation state of -2.0241

All those electrons that we took away from the breakdown of all these things - the carbohydrate, the fatty acid, the amino acids - they end up coming and reducing oxygen.0246

That is what they do, and in the process, of course, during these processes, CO₂ is also released.0254

Now, let's go ahead and just follow the electron path here.0260

I am going to do the electron path in red.0264

We have got some electrons from the citric acid cycle in the form of the NADH and the FADH₂.0268

In these cycles, in the glucose to pyruvate, pyruvate to acetyl-CoA and all the citric acid cycles, reactions that we are going to talk about, NADH is produced.0277

FADH₂ is produced; all those things come here, and they actually release their electrons.0287

Once they collect all of the electrons from the oxidations that they have done, they take their electrons, and they give them over to the electron transport chain; and that is what takes care of this.0292

Let's just follow the flow of electrons; remember, we had some NADH formed here?0303

Some electrons come here, and then, from here, there are going to be some electrons that come over here.0309

From here, there are going to be some electrons that come here; from here, there are going to be electrons that come here.0315

So, that is what these NAD and FAD coenzymes do; they are electron carriers.0320

They hold all of the electrons by oxidizing all of these things, and then, they dump their electrons onto the electron transport chain; so that those high-energy electrons can do work.0324

The work that they do, is they actually produce ATP, and they reduce oxygen to water.0334

That is what the body does; OK, this is the general scheme of what we are doing.0340

What we have done is we have taken care of glycolysis.0346

Today, what I am going to talk about in this lesson is we are going to discuss the conversion of the pyruvate that was formed during glycolysis.0350

We are going to talk about its transformation into acetyl-CoA by an absolutely extraordinary enzyme.0357

Really, it is truly fascinating what this does; it is unbelievable is what it does.0365

We are going to talk about that conversion of pyruvate to acetyl-CoA , and then, in the next lesson, we are going to start discussing the movement of acetyl-CoA into the citric acid cycle; and then, later on, in subsequent lessons, we are going to discuss the breakdown of fatty acids.0371

We are going to discuss the breakdown of the amino acids, and we will have covered this part right here.0387

And then, later, when we get to oxidative phosphorylation after that, we will discuss this part right here - the transfer of the electrons onto the electron transport chain - and then, we will have completed our basic catabolic movement.0394

Again, we did the glucose to pyruvate; today, we are going to do pyruvate to acetyl-CoA, so let's get started.0408

OK, now, from pyruvate to acetyl-CoA, let's go ahead and go to black here.0416

From pyruvate to acetyl-CoA- I will just write it as this for now, and then later, I will add the little S when we talk about the coenzyme A.0423

OK, pyruvate that is formed in glycolysis is oxidized to acetyl-CoA - and do not worry.0441

We will be drawing out all these structures in just a minute - in the mitochondrion.0455

This definitely takes place in the mitochondrion, not in the cytosol, by an amazing - and I do mean amazing - collection of enzymes - it is an aggregation of enzymes - called the pyruvate dehydrogenase complex.0462

I am telling you, when you see what this does, it is extraordinary.0492

And all this means is that it is a collection of enzymes that are aggregated together.0501

They are stuck together; they are not far away from each other to make sure that...because the product of one enzyme becomes the substrate to the next enzyme, and the product of that one becomes the substrate to the next enzyme.0506

They are all collected in one, sort of, huge enzyme complex.0516

It is called the pyruvate dehydrogenase complex, and the overall reaction that it catalyzes is the following.0520

The overall reaction goes as follows.0528

We have a molecule of pyruvate, and let's go ahead and draw the carbonyl vertically.0533

We have that, and we have CH₃; and it is converted to C, O, CH₃ - yes - S, CoA, and this S is a sulfur attached to the enzyme, the coenzyme A.0540

This is the ultimate conversion; pyruvate is converted to CoA, and here is how it happens.0566

Let's have something coming in, so what comes in is the acetyl-CoA; and I will write SH.0572

What also comes in and leaves is NAD⁺.0586

OK, there is going to be a dehydrogenation; there is going to be an oxidation - that is what this is - and it is going to release NADH + H⁺, and another thing that actually ends up leaving is CO₂.0590

Coenzyme A comes in; NAD⁺ comes in.0603

NADH leaves; CO₂ leaves.0607

The enzyme is the pyruvate; yes, I am just going to write PDH, so when we talk about...I am not going to keep writing it out.0614

We will just say PDH- pyruvate dehydrogenase.0621

We should say PDC, but it is PDH- pyruvate dehydrogenase.0626

The PDH or if you want to say PDHC, that is fine too; it does not really matter.0632

Now, in parentheses, I will write E1 + E2 + E3 because this is made up of a collection of 3 enzymes, multiple copies of each, so it is actually pretty extraordinary.0638

I will write multiple copies of each, and I will be talking about it in just a second; and we end up producing this.0651

This is our pyruvate molecule, and it is converted into acetyl-CoA, acetyl-S-CoA.0663

You are going to write acetyl-CoA, acetyl-S-CoA.0673

Some people write the S, some people do not; I am probably going to do both.0677

You will see why in just a minute; OK, the ΔG for this reaction...let's just go ahead and write the ΔG- -33.4kJ/mol.0679

This is irreversible; this is highly exergonic.0693

OK, this is the overall reaction that this pyruvate dehydrogenase complex actually catalyzes- the conversion of pyruvate to acetyl-CoA, so that it can enter the citric acid cycle.0697

Coenzyme A is used, NAD⁺.0711

Now, let's actually get into it; OK, this reaction is called oxidative decarboxylation, and is a decarboxylation - no, better learn how to spell here, wow, they really get into here - because CO₂ is removed.0715

This CO₂ group right here is lost; this CO₂ group is lost.0758

Decarboxylation, I am taking the C because CO₂ is removed or lost.0764

OK, oxidative because carbons' oxidation state actually changes, because carbons' oxidation state goes up.0771

You are normally decarboxylation and taking that something away from this carbon.0788

You are actually oxidating it some more, and here is how that looks.0792

I will describe this oxidation part; decarboxylation part is pretty clear.0798

It is the oxidation part that throws some kids off, so here is what is going on.0802

Let's take a look at pyruvate, so C, C, C.0806

That is that, and we have that; and we have CH₃.0811

The oxidation state of this carbon right here - OK - is...well, you have one carbon attached to it, another carbon attached to it, so that is 0 + 0, and you have a double bond to oxygen, so it is +1, +1, so it carries an oxidation state of +2.0816

Now, when you form the acetyl-CoA, you have that, and you have the S.0833

You have the CoA, and you have the CH₃.0838

Well, now, you have 1 carbon, which is 0; you have 2 oxygens - +1, +1 - to double bond, and then, you have sulfur.0842

Well, sulfur is more electronegative than carbon, so it is also considered...it is oxidizing the carbon.0849

It is taken away because sulfur and oxygen, they are in the same group.0854