Student: Do it.

Ahern: Do it.

[laughing]

I'm guessing if I gave everybody who came to class

an A today then they'd never come to class again.

That's just my hunch.

Which would kind of be a self-defeating thing, right?

So...

Student: Not necessarily.

Ahern: Maybe we would, right?

What she should say is, "Ahern, you're a scientist,

"let's do the experiment and fight out," right?

Student: Exactly.

Ahern: Well, we can't do that.

Student: You can give us extra credit.

Ahern: I could give you extra credit.

There's a lot of things I could do.

I could give you money.

[class laughing]

We could go have beer.

We could have pizza.

Student: How many of us would not get in

trouble for you buying beer.

Some of us are still under age, so...

Student: Yeah, you could get in a lot of trouble.

Ahern: No, actually the way I do that is I go to a place

where they can serve people underage

and you have to show an ID so it's not my responsibility.

A lot of energy.

I hope everybody's got a big Thanksgiving planned.

Wild plans?

Student: Family.

Ahern: Oh.

Family, huh?

Like I said, if any of you are in town

and would like to come over, give us a holler

and I'll let you know where we're going to live and everything,

but if you'd like to come over,

we've got plenty of turkey and other things.

And no, I won't get you drunk.

But we'll have a good time.

Today we're going to have a good time

because we're going to be thinking of the making of glucose.

I know that for many of you,

that's been something you've dreamed of doing

and you're going to get that dream today.

Happy days are here again.

Glucose synthesis is an interesting process.

The phenomena of course is known as gluconeogenesis

and it is a pathway that is very similar,

very similar to glycolysis.

Very similar.

It's very similar to the reverse of glycolysis.

However, there are important differences and specifically,

there are two reactions.

I'm sorry, specifically that there are 3 reactions.

There are 3 reactions in gluconeogenesis,

in glycolysis that are replaced

by 4 reactions in gluconeogenesis.

So gluconeogenesis has 11 steps, glycolysis had 10.

One of the steps takes two steps to get around.

So it's 2 step.

If you learned glycolysis, gluconeogenesis for 8 of the steps,

Let's get that right for 7 of the steps.

I can't get my head right today.

for 7 of the steps is identical to glycolysis

except for in the reverse.

Same enzymes, same intermediates going to the opposite direction.

Three of the steps that are in glycolysis

as I said are replaced by 4 steps.

So let's take a quick look at that.

Before I take a look at that, I'll show you something

your book is distracted by and that is this process here,

which is the making of glucose from glycerol.

Why do we care about the making of glucose from glycerol.

One of the reasons we care about the making of glucose

from glycerol is glycerol is a byproduct

of fat metabolism and so it turns out

that the only portion of the fat molecule

that can be converted directly into glucose is the glycerol.

We don't convert fat into glucose for the most part,

with the exception of the glycerol.

I just show you this, I'm not going to go through

and expect you to memorize these are anything,

but just show you that glycerol is a 3-carbon molecule.

It gets made in a couple of reactions

into an intermediate in glycolysis,

dihydroxyacetone phosphate.

And of course, once it's dihydroxyacetone phosphate,

we can now do the upwards pathway,

going into making glucose via gluconeogenesis.

And we see this, this is a phenomena you've seen before.

We saw how other sugars entered glycolysis

and gotten broken down by being converted

into glycolysis intermediates.

We saw, for example, fructose got converted

into fructose-6-phosphate and then got metabolized

as an intermediate in glycolysis.

In this case, we see glycerol being converted

into an intermediate in glycolysis or gluconeogenesis,

it can actually go either way,

and be made into either glucose or ultimately into pyruvate.

Let's focus on gluconeogenesis

since that's our main topic of the day.

You'll notice in looking at the screen

that we oriented very much like we oriented glycolysis

except that we're going upwards in gluconeogenesis

where as we were going downwards in glycolysis.

So we start at the bottom and the place where we will

start gluconeogenesis is actually pyruvate.

But again, we remember that all these designations

about where something starts and stops is really arbitrary.

We could just as easily start it at lactate

for some types of metabolism.

We can start at amino acids as well,

but we're going to start right here at pyruvate.

So starting at pyruvate, and that's a good place to start

because that's where we finished glycolysis,

starting with pyruvate, cells can convert pyruvate into glucose.

Well, not surprisingly, if pyruvate is a 3-carbon molecule

and we want to make a 6-carbon glucose,

we need to have two pyruvates to start everything.

We're going to start with 2 of everything

and eventually they're going to combine

into 1 as we get higher up in the pathway.

What we discover in gluconeogenesis is the first

instance that we see of a phenomenon I call

sequestration meaning we're sequestering something.

All of glycolysis occurs in the cytoplasm of the cell.

All of the enzymes of glycolysis are found

in the cytoplasm of the cell.

In the case of gluconeogenesis, we see 2 enzymes

that are not found in the cytoplasm of the cell.

These are sequestered into other organelles

in the cell and I'll show you those.

They actually end up being the first

and the last enzyme in the pathway.

All the other enzymes between the first and the last

are all found in the cytoplasm.

Let's look at what's happening in making glucose from pyruvate.

If we recall in glycolysis, in going from PEP to pyruvate,

I said that was the big bang.

I said that was a reaction that was extraordinarily energetic.

It had a large delta-G-zero prime.

And as a consequence, that,

you might imagine going in the reverse direction,

would be an enormous energy barrier to overcome.

And in fact, that's exactly what it is.

It's because of this enormous energy barrier

that cells can't go directly back from making

pyruvate to PEP in one step.

They have to do a two step around it.

And the two steps around it are these two enzymes here.

Pyruvate carboxylase and phosphoenolpyruvate carboxykinase,

which you are more than welcome to abbreviate as PEPCK.

Let's talk about the first one first,

pyruvate carboxylase is an enzyme that is found

in the mitochondrion of cells.

It's not found in the cytoplasm.

The very first reaction of gluconeogenesis

occurs in the mitochondrion, not the cytoplasm.

In this reaction, as you can see on the screen,

carbon dioxide in the form of bicarbonate and ATP

are used to convert pyruvate into oxaloacetate.

You can see the structure here.

Here's a 3-carbon, here's a 4-carbon over here.

We've put an additional carboxyl group onto the end of pyruvate.

The carboxyl group going right here.

We can see the new carboxyl group on the right side.

Here it was what pyruvate looked like over here.

So what we did is we took this methyl group

and we added a carboxyl group to it.