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Gluconeogenesis I

Lecture Slides are screen-captured images of important points in the lecture. Students can download and print out these lecture slide images to do practice problems as well as take notes while watching the lecture.

  • Intro 0:00
  • Gluconeogenesis, Part 1 1:02
    • Gluconeogenesis Overview
    • 3 Glycolytic Reactions That Are Irreversible Under Physiological Conditions
    • Gluconeogenesis Reactions Overview
    • Reaction: Pyruvate to Oxaloacetate
    • Reaction: Oxaloacetate to Phosphoenolpyruvate (PEP)
    • First Pathway That Pyruvate Can Take to Become Phosphoenolpyruvate
    • Second Pathway That Pyruvate Can Take to Become Phosphoenolpyruvate
    • Transportation of Pyruvate From The Cytosol to The Mitochondria
    • Transportation Mechanism, Part 1
    • Transportation Mechanism, Part 2
    • Transportation Mechanism, Part 3
    • Transportation Mechanism, Part 4

Transcription: Gluconeogenesis I

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

In the last several lessons, we discussed glycolysis, and we finished discussing glycolysis.0004

Today, we are going to start talking about gluconeogenesis, which is instead of the breakdown of glucose, this is how the body actually makes glucose when it needs to do so.0011

Now, you are going to see in a minute that a lot of the reactions of gluconeogenesis are the same.0020

They are just run in reverse, however, it is not just glycolysis run in reverse.0026

If you remember in the glycolysis reactions, there are 3 reactions in particular that were highly exergonic, very, very high negative free energy.0030

They are virtually irreversible under physiological conditions.0038

Well, because they are irreversible; there is no way for the enzymes to actually go backward, just reverse glycolysis.0042

Those particular reactions, gluconeogenesis actually bypasses and uses its own set of enzymes for its metabolic pathway.0049

Let’s go ahead and write all these down formally and see what is going on.0057

OK, so let’s see; we will stick with black today.0063

Often times, the body needs to synthesize glucose instead of breaking it down.0071

OK, so we will concentrate on the gluconeogenesis that takes place in the mammalian liver.0099

We will concentrate on how the mammalian liver does this.0110

OK, so gluconeo - I will just call it that for short - gluconeogenesis is not the reverse of glycolysis, not just the reverse of glycolysis.0125

OK, now, we can start; recall, there are 3 glycolytic reactions that are irreversible under physio conditions.0151

OK, let’s go ahead and list what they are.0182

The first one, we have glucose going to glucose 6-phosphate.0187

We had a ΔG, and in parentheses, I will just write physio ΔG; and notice, there is no standard, no degree sign noted.0193

These are actually under physiological conditions, not biochemical standard conditions, so negative, somewhere in the range of -33kJ/mol; and then, the second reaction is going to be the fructose 6-phosphate to the fructose 1,6-biphosphate.0201

That one carries a ΔG of about -22kJ/mol, and the last is the phosphoenolpyruvate to pyruvate.0230

That is the final reaction in the glycolytic sequence, and this one carries a ΔG of, under physio conditions of about -16, -17kJ/mol- all of them irreversible.0245

Gluconeogenesis has to bypass these reactions.0257

It cannot just use these reactions; excuse me.0261

Gluconeogenesis bypasses these steps with its own set of enzymes, and these reactions are, themselves, sufficiently exergonic to make sure that gluconeogenesis is irreversible.0267

Well, are sufficiently exergonic to make sure that gluconeogenesis - well, let me go ahead - to make sure that they are irreversible in themselves.0329

They are irreversible; it is the reactions that are irreversible.0340

Essentially, it is going to commit to gluconeogenesis; it is not going to back down somewhere in the middle.0343

These particular reactions, themselves, are highly exergonic to push gluconeogenesis forward.0350

Sure that they are irreversible, themselves- let’s just go ahead and say it that way.0356

OK, so let’s go ahead and take a…we are going to look back at a schematic - well, I am going to draw it out - of glycolysis, and I will show you where the bypass reactions take place.0362

Let’s go ahead and do this one in…let me go ahead…well, you know what, I will just stick with black for the time being.0371

Here are the steps of glycolysis; I am hoping I can get this all in one page.0378

Let me see; I have got glucose to glucose 6-phosphate.0383

I am going to use just some short-hand notation here, glucose 6-phosphate to fructose 6-phosphate, and then, to fructose 1,6-biphosphate; and at that point, we go to glyceraldehyde-3-phosphate.0390

I will write glyceraldehyde-3-phosphate, and we also produced a - I will do it over here, that is OK, I will do it over here -dihydroxyacetone phosphate, which, itself, is converted to the glyceraldehyde-3-phosphate.0405

We produced 2 molecules - right - out of the glyceraldehyde-3-phosphate from the 1 molecule of glucose, and then, we start the second phase.0420

We go to 1,3-biphosphoglycerate, and then, we go to 3-phosphoglycerate, then we go to 2-phosphoglycerate, then we go to phosphoenolpyruvate; and, of course, our final step is 2 molecules of pyruvate.0427

OK, these are going to be the bypass steps; let me go and do these in red.0448

The glycolysis is this way; gluconeogenesis, we are going to run this way, and here is what happens.0452

The conversion from pyruvate to phosphoenolpyruvate, as we go back, it takes place in a 2-step process.0457

The first step is actually going to form oxaloacetate, and then from oxaloacetate, that one is going to go to phosphoenolpyruvate.0463

Now, let me go ahead and I will write the enzymes in blue.0479

The conversion of pyruvate to oxaloacetate takes place under the guidance of an enzyme called pyruvate carboxylase, and the conversion from oxaloacetate to phosphoenolpyruvate takes place under an enzyme called PEP carboxykinase or carboxykinase.0483

Again, it depends on how you want to pronounce it; it does not really matter.0505

OK, now, let’s go back to red.0511

Now, the second bypass step is going to be from the fructose 1,6-biphosphate to the fructose 6-pospahate.0515

This one goes like that, and its enzyme is fructose 1,6-biphosphatase.0520

It takes away a phosphoryl group, and the last bypass step is the one from glucose 6-phosphate to glucose; and that one - exactly what you think - it is glucose 6-phosphatase- there you go.0540

Glycolysis runs this way; gluconeogenesis runs this way.0563

All of the enzymes, all of these other reactions, are the reverse of glycolysis because these reactions under physiological conditions, the ΔG is very, very close to 0.0567

If it is not 0 itself, it is very close to 0; it is irreversible.0577

Remember we had double arrows for most of them, but for this one, this one and this one- irreversible.0581

It needs another set of enzymes to make sure they run this way.0586

And again, these reactions running in this direction up towards glucose, each of these is efficiently exergonic to make sure that gluconeogenesis pushes forward.0590

It is fantastic that it actually does this; OK, now, let’s go ahead and take a look at the individual reactions.0599

We are going to go ahead and start with this bottom one- the pyruvate carboxylase and the PEP carboxykinase.0605

Let’s write out the reactions, and then, we will talk about the mechanism.0612

I am not sure about the extent to which your teachers are going to actually have you learn mechanisms.0617

I think there are going to be certain set of reactions; you are limited in time, whether you are taking a quarter system class or whether you are taking a semester system class.0622

So, I am guessing only a handful of mechanisms are the ones that you are going to be needing.0630

In this particular course in biochemistry here at Educator, I am going to tend to place a lot of the mechanisms.0635

I am going to show them simply for the sake of…I think it is really, really important that you understand and become comfortable with mechanistic biochemistry, with the mechanism of organic chemistry.0642

Those of you that go on particularly into research and or pharmacy school or things like that, mechanisms are going to be a big part of what you do, at least academically.0653

It is important to become comfortable with those things; I want you to see as many of them as possible.0663

OK, having said that, let’s go ahead and write the reactions down.0667

Let me go ahead and write the reactions in blue here.0673

The first one is going to be…so again, a 2-step from pyruvate to phosphoenolpyruvate.0677

The first one is going to be like this.0689

That is fine; OK, we will go C, C, C.0699

This is there; I will go ahead and put the double bond up here, the CH3 there.0706

OK, this is going to be plus; it is going to be H, O, C, O, O-.0712

This is going to be bicarbonate; well, let me go ahead and write the reaction first and then I will…OK, ATP is going to come in.0719

ADP and PI are going to leave; the coenzyme biotin is going to be very, very necessary in this particular reaction, and then, of course, the enzyme itself is, as we said, pyruvate carboxylase.0732

OK, now, it is going to form the oxaloacetate, which is going to be C, C, C, C.0751

We have this; we have that, and we have, of course, this carboxy group that we put on there, and let me…well, that is fine.0761

I will go ahead and put the Hs on also; it is not all together that big a deal.0774

In red, let me write, this is oxaloacetate.0779

This is bicarbonate - bicarbonate or bicarbonate - and this is our pyruvate.0785

OK, and again, this enzyme biotin, this is going to be the next to the coenzymes of vitamins that we are going to be discussing in just a little bit - very, very important - and the enzyme for this is pyruvic carboxylase.0793

OK, let me go ahead and write the second reaction, and then, we will jump into the mechanism.0809

The second reaction is, now, we are going to take this oxaloacetate, so C, C, C, C.0813

I am going to leave off the hydrogens in this one; I hope you guys do not mind.0820

Again, anytime you see a carbon that has nothing attached to it or seems to be missing some things, just attach a hydrogen to it.0824

This is there, and this is there.0830

This is our oxaloacetate, and we are going to add to this not adenosine triphosphate but a guanosine triphosphate.0834

Interestingly enough, this goes that way.0841

GDP - guanosine diphosphate - actually ends up leaving; in this particular step, CO2 is lost.0847

The CO2 that we added is now, lost, and the enzyme for this is PEP carboxykinase; and our final molecule is the phosphoenolpyruvate.0853

We have our C; we have our C.0868

We have our C; this is, of course, a double bond there.0872

We have our group there; we have our oxygen, and we have our phosphate.0875

I will just go ahead and put PO32-.0881

This is our oxaloacetate.0885

This is our GDP; I will just go ahead and leave that there, and this is our phosphoenolpyruvate- our PEP.0889

Pyruvate to oxaloacetate, oxaloacetate to phosphoenolpyruvate- 2 bypass steps, OK?0895

Alright, let me go ahead and just circle this.0902

Notice that CO2 comes in in the form of bicarbonate.0906

CO2 leaves in the form of CO2; now, let’s talk about the mechanism.0910

Actually, you know what, before I talk about the mechanism, I am going to…well, here, I will just go ahead and talk about it.0916

OK, so let’s do this one in red.0924

Now, there are 2 pathways for pyruvate, 2 pathways that pyruvate can take to become phosphoenolpyruvate in the gluconeogenesis.0928

OK, there are 2 paths that it can actually take.0960

A pyruvate is not the only precursor to gluconeogenesis.0964

Pyruvate is the first molecule that enters the cycle, but there are several other molecules that can actually act as precursors to pyruvate depending on, if it is directly pyruvate that goes into gluconeogenesis, it is going to take a particular pathway.0968

If it is not pyruvate in this thing that I am going to draw, if it happens to be lactate that is converted to pyruvate, it actually takes a different pathway.0985

It is almost similar; it takes place in the same place physically, but it is a different pathway.0992

Let me go ahead and talk about those, and I will discuss both.1000

Let me see if I can…OK, I will try to make it as big as possible.1005

This is going to be our mitochondrion, and this is where it actually is going to take place.1011

Now, actually, you know what, I am going to need a little bit more room here.1019

OK, let me go ahead and go a little bit lower here.1034

I hope I can squeeze it all in; I am sure I can.1040

Alright, let me just take a couple of minutes to draw this here; we have pyruvate over here.1045

This is going to be one pathway, and I will go ahead and put a pyruvate over here too.1049

This is going to be another pathway; this one, what is going to happen here is, I will go ahead and write pyruvate again.1053

I will go ahead and write oxaloacetate there, and then, I will bring it back down here.1065

I will write malate, and I will do this.1078

I will do malate; I will do oxaloacetate, and then, I will go to our phosphoenolpyruvate.1084

And over here, I am going to come from lactate, and again, I will come to pyruvate.1095

OK, and I will go to this one; I will go to oxaloacetate.1105

And from oxaloacetate, I will go to phosphoenolpyruvate and phosphoenolpyruvate to there.1118

OK, the first one, I am going to discuss when I discuss the mechanism is going to be this one right here.1125

It is going to be the one on the left when pyruvate is directly the precursor to gluconeogenesis.1129

Now, let me go ahead and finish some of these by actually drawing in some things that come in and some things that leave.1135

CO2 comes in; this is going to be step 1.1145

And then, over here, we have NADH + H+ comes in, and NAD+ leaves.1151

And then, from malate to oxaloacetate, we have NAD+ coming in and NADH + H+ goes there.1167

And over here, this is where the CO2 - OK - leaves.1180

Now, let me go ahead and write some enzymes here.1186

In step 1, we have the pyruvate oxaloacetate.1190

That is going to be our pyruvate carboxylase, and over here, this is going to be mitochondrial malate dehydrogenase.1194

OK, over here, this is going to be cytosolic.1223

I will write malate - D-E-H - dehydrogenase.1230

This is the same reaction, except one of the enzymes actually does it in the mitochondria.1234

The other one does it in the cytosol, so these are different.1238

OK, and, of course, the last enzyme, this was the cytosolic phosphoenolpyruvate carboxykinase.1243

That is the second step of our particular reaction.1255

OK, now, over here, this is what is, kind of, important.1260

Let me go ahead and go back to red.1264

NAD+ comes in, and NADH + H+ leaves.1268

This is step 1; this is step 2.1278

Here, this is lactate dehydrogenase.1284

And again, I will be talking about all of this in just a little bit, but I want you to have...I am just going to go through a quick rundown of what it is that is going on, and then, we will discuss it in detail.1289

Here, it is going to be the same; it is going to be the pyruvate carboxylase.1300

Here, it is going to be...this enzyme right over here that catalyzes that step, this is called mitochondrial PEP carboxykinase.1304

OK, let's stop and take a look at what is going on here.1325

Basically, in the pathway that we are going to follow, the pyruvate is actually transported into the mitochondrion.1329

The pyruvate is converted into oxaloacetate, the normal reaction, but because the mitochondrion does not have an active transporter, it does not have a way of actually bringing in or taking out the oxaloacetate molecule.1336

What it has to do is it actually converts it into malate, and then, it sends the malate out of the mitochondrion; and then, it reconverts it back to oxaloacetate.1350

Once it gets to oxaloacetate, then, it is back in the cytosol.1362

Now, the cytosolic PEP carboxykinase converts it to PEP.1365

However, if lactate is the actual precursor molecule, and lactate is, first of all, converted to pyruvate and the same thing, pyruvate is brought into the mitochondrion, now, in this case, pyruvate is converted to oxaloacetate via the pyruvate carboxylase reaction.1370

While it is in the mitochondrion - OK - it actually just goes ahead and directly converts it to the phosphoenolpyruvate.1388

This time, this reaction is mitochondrial PEP carboxykinase versus this one that actually takes place in the cytosol.1395

In this pathway, the second part of that bypass reaction from pyruvate to phosphoenolpyruvate, the first step takes place in the mitochondrion.1404

The second step takes place in the cytosol; in this other pathway, both steps takes place in the mitochondrion, and then, of course, it just sends out the PEP into the cytosol to continue on with the gluconeogenesis.1412

The first one we are going to talk about is this one; the mechanisms are essentially the same.1425

I mean, these are just isozymes; they are the same enzyme.1430

They are not the same enzyme; they are the enzymes that actually catalyze the same reaction, but they are encoded by different genes of the DNA.1435

That is all that is going on here; I just wanted you to see that there are 2 different pathways depending on the precursor molecule- pyruvate directly or something that is not pyruvate directly if the pyruvate happens to come from lactate.1441

OK, now, let's go ahead and talk about the mechanism.1456

OK, let me go back to black here.1461

Again, let's see.1465

Pyruvate is transported from the cytosol to the mitochondrion.1470

OK, let me write the reaction one more time; what we have is - oops, that is OK, I will go ahead and leave it in blue - C, C, C.1495

We have this; we have that.1508

We have our pyruvate molecule, and we are going to add to this H, O, C.1511

Bicarbonate is going to be the other reactant in this, and we are going to end up with our C, C, C, C.1519

That is there; that is there, and let me see.1528

What am I missing?1532

I have my...that, and, of course, I will go ahead and just leave off the hydrogens.1536

That is going to be our oxaloacetate, and what is going to come in is ATP.1540

What is going to leave is ADP + PI.1545

When you see ATP come in and ADP and PI leaves, that means the phosphoryl group does not stay on the molecule.1549

That means that the energy on ATP is being used to drive this reaction- that is what is going on here.1557

ATP comes in, both products of ATP, which is ADP and PI, both of them end up leaving.1564

What is really coming into this reaction is the energy of ATP.1571

And again, we have biotin, is the coenzyme that is necessary; and we have the pyruvate carboxylase.1575

OK, now, let's go ahead and run through the mechanism.1586

There is going to be little bit of, well, a fair amount of drawing here; the mechanism is not necessarily complicated, but it is a little involved.1589

Let me go ahead and do the mechanism know what, I will just keep it in blue- not a problem.1596

I will try to do the electron movements in red, if I remember.1604

OK, let's go ahead and start drawing what we have got here.1609

Let's go ahead and do…we have: a D-ribose phosphate, phosphate.1613

And this last one, I will actually draw in because it is necessary to draw it in.1624

And over here, I am going to draw out my bicarbonate.1631

OK, now, I will draw this.1640

OK, this is going to be catalytic site 1.1648

There are 2 catalytic sites on this particular enzyme, the pyruvate carboxylase.1652

Part of the reaction takes place in one part, and then, the other part takes place in the second site.1657

This is catalytic site 2, and you will see how this biotin does this extraordinary, extraordinary thing.1662

It is absolutely fantastic.1671

OK, let me go ahead and I am probably going to need a little bit more room here, but that is OK.1675

I will do lysine, and then, we have our N, COO, then 1, 2, 3, 4, 5...let's see.1680

We are going to have a 1, 2, 3, 4, 5, 1, 2, 3, 4, there is a sulfur.1695

There is a nitrogen; there is a nitrogen.1705

There is a carbonyl; we have an H.1707

We have an H, and OK.1711

This is how it begins; you have the enzyme, which is this thing right here.1715

OK, and attached to a lysine residue is this biotin molecule, this biotin coenzyme.1722

So, it is going to be involved, and what it is actually going to end up doing is, whatever ends up happening over here, it is going to take this molecule.1730

See this long arm?1737

It actually acts as a tether; it actually moves things from one place to another place on the enzyme.1740

It is going to end up swinging and bringing whatever is formed over here over to this side, so that a particular reaction can take place over there.1744

This is absolutely fantastic, and this is not the only time we will see this.1752

We will see this another time later on with a different coenzyme.1756

Before we begin, this is how it starts; now, let's go ahead and do some electron movements here.1761

Let me do these in red; this is going to be just a standard SN 2.1766

This comes over here and does that and does that, and in the process, what it ends up doing is...I am going to go ahead and write it this way.1771

ADP actually leaves in this reaction, and what you end up getting is, you get H, O, C, O, and then, P, O, O, O.1788

This is what we have; this phosphate, right here, this phosphoryl group, is now attached here.1804

That is this one, right here, OK?1810

That happens there; now, I will go ahead and do - since I have written this in red - the electron movements in black.1814

There are electrons on here; what happens is these electrons and oxygen, CO2 is a molecule that very, very, very badly wants to be formed.1823

It goes like that, and it kicks away the actual full phosphate molecule; and then, this hydrogen breaks off.1832

It just leaves, and what you are left with is CO2; what you are left with, at this point, is the following.1841

Now, let's go ahead and draw our site again.1852

Yes, that is fine; I guess I have got enough room here.1857

We have that; we have our lysine.1861

We have our nitrogen, 1, 2, 3, 4, 5.1865

We have our carbonyl; we have that, that, that, that, that.1871

There is an S there; we have another 5-membered ring.1875

There is a nitrogen; there is a nitrogen.1878

There is an H; there is an H, and there is our carbonyl.1880

And now, what we have is this carbon dioxide molecule, right?1885

We ended up forming a carbon dioxide molecule over here in site 1.1890

That is that; now, what is going to happen is these electrons - oops, let me do this in red - on nitrogen - they are nucleophilic - they are going to actually attack the electrophilic carbonyl - happens all the time - and you are going to end up with that.1895

Let me actually go back to black; this is the enzyme just to make sure we know what is happening, and this is site 2.1912

OK, now, what happens is it attacks here; now, this COO is attached to the nitrogen.1921

This H ends up leaving.1928

OK, it releases an H+; now, what you have is the following.1932

Now, what you have is...let me draw it down here, so we have some room.1938

This is site 1; this is site 2.1942

We have our lysine.1947

We have our nitrogen, and we have 1, 2, 3, 4, 1, 2, 3, 4, 5.1953

That is going to be there; we have this.1964

We have a sulfur; we have N.1970

We have N; we have a carbonyl, and now, what we have is this COO- that is covalently attached to the biotin molecule, and all of this is happening over here at site 1.1974

Now, what happens is this long arm tether, it takes it from site 1.1986

It moves it over to site 2; it flips around, so we can now, expose this CO2 to what is happening over here in site 2.1994

I will draw it like this; this swings over to site 2.2001

It is absolutely fantastic, this biological tether.2011

Just a simple carbon chain- that is all it is, and it can do this; and it is amazing.2015

It is a huge distance that can actually cover these biological tethers.2021

OK, now, when it swings over to this side, now, it is going to turn over and expose this carbon dioxide that is attached here over to site 2.2025

Now, let's see what it looks like; let me go back to black.2036

This is our enzyme just to make sure we remember.2039

OK, now, we are looking like this.2045

Let me draw it down here; now, reactions are taking place in site 2.2055

We have our lysine; we have our N, 1, 2, 3, 4, 5.2062

Now, notice, the carbonyl is on this side, and I have got my 5-membered rings here, my carbonyl.2070

I have my nitrogen; I have my nitrogen.2080

I have my COO- attached there; I have my sulfur.2082

Hopefully, I have not forgotten anything; again, like I said, there are so many atoms floating around that it is very, very possible that I forgot, and I hope that you are actually confirming many of these structures for me.2086

Now, at this point, what happens is the following.2098

This actually breaks off from the biotin.2102

This goes like that, and what we end up getting, what happens, when that happens, now, CO2 is free over here at site 2.2107

It is free to react, and this is where pyruvate comes in.2120

C, C, C, O-, O, and I am going to actually draw out all of the Hs here this time.2126

So, that comes in, and now, what happens is the following.2137

When that comes in, then we get...let me go back to black.2151

OK, we have lysine, N, 1, 2, 3, 4, 5.2159

That is there, and we have 1, boom, boom, boom, boom, boom, boom.2169

That is there; this is a nitrogen.2176

This is a nitrogen; this is a sulfur.2179

Oops, sorry; what did I do?2183

Oh, sorry about that; I need to actually form…I am in black, right?2189

Yes, I am in black; this is a carbonyl here.2195

What happens is it does not actually go on to the nitrogen; well, it can.2199

It does not really matter how you do this; I mean, you can put the electrons on the nitrogen, or it is more conventional to put them in terms of a double bond; so you end up with something like that.2204

Now, what you actually end up here is this thing.2215

The electrons are on the oxygen, negative charge.2220

The electrons here- double bond, and then, of course, you have your CO2 molecule, which broke off; and then, of course, you have your pyruvate molecule, which is now, in the catalytic site 2.2223

OK, and this is site 1; now, what ends up happening is the following.2245

These electrons move back down to form the carbonyl; these electrons over here grab one of the Hs on the pyruvate.2250

They push this bond over to here, and they push these up to here.2258

Again, boom, boom, takes a hydrogen, sorry, I should attach a hydrogen here.2265

There we go; this takes that hydrogen because it wants it, pushes the electrons this way to form the enol.2274

This goes up that way; that is what is happening here.2282

OK, now, once this happens, what you end up with is the following.2286

Let me go back to black; now, let me go to my next page.2293

OK, let me go to my next page, alright.2299

Alright, now, I have my lysine.2306

I have this 1, 2, 3, 4, 5.2312

Let me just go ahead and draw this in, boom, boom, boom, nitrogen, nitrogen.2317

Carbonyl is reformed; this is sulfur.2324

There is my carbonyl; now, I have my CO2.2327

I lost my - change of color, so forgive me - COO there, and now, I have a C.2332

I have H2; there is a double bond here.2344

There is a negative charge there; there is a C there.2347

This is my pyruvate; OK, now, what happens is the following.2352

Again, this is site 2; this comes back down here.2357

This will attack that one; this will push something there like that, and then, of course, what you end up with is the release by the enzyme at this point.2363

And now, notice what you have got; now, this comes down, pushes these electrons from the double bond to attack the carbon of the carbon dioxide, which is electrophilic.2379

It pushes these over here, so now, the negative charge ends up over here; and what you end up with is C, C, C, C.2390

You end up with that.2400

Oops, and I will go ahead and put the Hs here.2405

You end up with your oxaloacetate.2411

There you go; this CO2 right here, that is what was brought in as bicarbonate.2417

The bicarbonate reacted with the ATP, and got itself a phosphate group to activate it; and then, it went ahead and lost its phosphate group.2427

Now, it is free in site 1; it reacted with the biotin.2440

The biotin moved it over to site 2; it released the CO2.2445

It roamed around freely in site 2; it took in the pyruvate molecule.2450

Well, a pyruvate gave up one of its hydrogens to the biotin, to recover the biotin, and then, at that point, it has been activated in this form to actually react with the CO2 to add this carboxyl group to the other end of the pyruvate to form oxaloacetate- an absolutely extraordinary mechanism.2460

There you have it; this is the first half of the bypass reaction for the first step of gluconeogenesis.2479

I am going to stop this lesson here; in the next lesson, we will continue on with the rest of it.2485

Thank you so much for joining us here at; we will see you next time, bye-bye.2491