Krebs / Citric Acid Cycle

So we already know that if we
start off with a glucose

molecule, which is a 6-carbon
molecule, that this

essentially gets split in half
by glycolysis and we end up 2

pyruvic acids or two
pyruvate molecules.

So glycolysis literally
splits this in half.

It lyses the glucose.

We end up with two pyruvates
or pyruvic acids.

ruby And these are 3-carbon
molecules.

There's obviously a
lot of other stuff

going on in the carbons.

You saw it in the past. And
you could look up their

chemical structures on the
internet or on Wikipedia and

see them in detail.

But this is kind of the
important thing.

Is that it was lysed,
it was cut in half.

And this is what happened
in glycolysis.

And this happened in the
absence of oxygen.

Or not necessarily.

It can happen in the presence
or in the absence of oxygen.

It doesn't need oxygen.

And we got a net payoff
of two ATPs.

And I always say the net there,
because remember, it

used two ATPs in that investment
stage, and then it

generated four.

So on a net basis, it generated
four, used two, it

gave us two ATPs.

And it also produced
two NADHs.

That's what we got out
of glycolysis.

And just so you can visualize
this a little bit better, let

me draw a cell right here.

Maybe I'll draw it down here.

Let's say I have a cell.

That's its outer membrane.

Maybe its nucleus, we're
dealing with

a eukaryotic cell.

That doesn't have
to be the case.

It has its DNA and its chromatin
form all spread

around like that.

And then you have
mitochondria.

And there's a reason why people
call it the power

centers of the cell.

We'll look at that
in a second.

So there's a mitochondria.

It has an outer membrane
and an inner

membrane just like that.

I'll do more detail on the
structure of a mitochondria,

maybe later in this video
or maybe I'll do a

whole video on them.

That's another mitochondria
right there.

And then all of this fluid,
this space out here that's

between the organelles-- and
the organelles, you kind of

view them as parts of the cell
that do specific things.

Kind of like organs
do specific things

within our own bodies.

So this-- so between all of the
organelles you have this

fluidic space.

This is just fluid
of the cell.

And that's called
the cytoplasm.

And that's where glycolysis
occurs.

So glycolysis occurs
in the cytoplasm.

Now we all know-- in the
overview video-- we know what

the next step is.

The Krebs cycle, or the
citric acid cycle.

And that actually takes place
in the inner membrane, or I

should say the inner space
of these mitochondria.

Let me draw it a little
bit bigger.

Let me draw a mitochondria
here.

So this is a mitochondria.

It has an outer membrane.

It has an inner membrane.

If I have just one inner
membrane we call it a crista.

If we have many, we
call them cristae.

This little convoluted
inner membrane, let

me give it a label.

So they are cristae, plural.

And then it has two
compartments.

Because it's divided by
these two membranes.

This compartment right here is
called the outer compartment.

This whole thing right there,
that's the outer compartment.

And then this inner compartment
in here, is called

the matrix.

Now you have these pyruvates,
they're not quite just ready

for the Krebs cycle, but I
guess-- well that's a good

intro into how do you
make them ready

for the Krebs cycle?

They actually get oxidized.

And I'll just focus on one
of these pyruvates.

We just have to remember that
the pyruvate, that this

happens twice for every
molecule of glucose.

So we have this kind
of preparation step

for the Krebs Cycle.

We call that pyruvate
oxidation.

And essentially what it does
is it cleaves one of these

carbons off of the pyruvate.

And so you end up with
a 2-carbon compound.

You don't have just two carbons,
but its backbone of

carbons is just two carbons.

Called acetyl-CoA.

And if these names are
confusing, because what is

acetyl coenzyme A?

These are very bizarre.

You could do a web search on
them But I'm just going to use

the words right now, because it
will keep things simple and

we'llget the big picture.

So it generates acetyl-CoA,
which is

this 2-carbon compound.

And it also reduces some
NAD plus to NADH.

And this process right here is
often given credit-- or the

Krebs cycle or the citric
acid cycle gets

credit for this step.

But it's really a preparation
step for the Krebs cycle.

Now once you have this 2-carbon
chain, acetyl-Co-A

right here.

you are ready to jump into
the Krebs cycle.

This long talked-about
Krebs cycle.

And you'll see in a second
why it's called a cycle.

Acetyl-CoA, and all of this
is catalyzed by enzymes.

And enzymes are just proteins
that bring together the

constituent things that need to
react in the right way so

that they do react.

So catalyzed by enzymes.

This acetyl-CoA merges with
some oxaloacetic acid.

A very fancy word.

But this is a 4-carbon
molecule.

These two guys are kind of
reacted together, or merged

together, depending on how
you want to view it.

I'll draw it like that.

It's all catalyzed by enzymes.

And this is important.

Some texts will say, is this an
enzyme catalyzed reaction?

Yes.

Everything in the Krebs
cycle is an

enzyme catalyzed reaction.

And they form citrate,
or citric acid.

Which is the same stuff
in your lemonade

or your orange juice.

And this is a 6-carbon
molecule.

Which makes sense.

You have a 2-carbon
and a 4-carbon.

You get a 6-carbon molecule.

And then the citric acid
is then oxidized

over a bunch of steps.

And this is a huge
simplification here.

But it's just oxidized over
a bunch of steps.

Again, the carbons
are cleaved off.

Both 2-carbons are cleaved
off of it to get back to

oxaloacetic acid.

And you might be saying, when
these carbons are cleaved off,

like when this carbon
is cleaved off,

what happens to it?

It becomes CO2.

It gets put onto some oxygen
and leaves the system.

So this is where the oxygen or
the carbons, or the carbon

dioxide actually gets formed.

And similarly, when these
carbons get cleaved

off, it forms CO2.

And actually, for every molecule
of glucose you have

six carbons.

When you do this whole process
once, you are generating three

molecules of carbon dioxide.

But you're going
to do it twice.

You're going to have six carbon
dioxides produced.

Which accounts for all
of the carbons.

You get rid of three carbons
for every turn of this.

Well, two for every turn.

But really, for the steps after
glycolysis you get rid

of three carbons.

But you're going to do it for
each of the pyruvates.

You're going to get rid of all
six carbons, which will have

to exhale eventually.

But this cycle, it doesn't
just generate carbons.

The whole idea is to generate
NADHs and FADH2s and ATPs.

So we'll write that here.

And this is a huge
simplification.

I'll show you the detailed
picture in a second.

We'll reduce some NAD
plus into NADH.

We'll do it again.

And of course, these are
in separate steps.

There's intermediate
compounds.

I'll show you those
in a second.

Another NAD plus molecule
will be reduced to NADH.

It will produce some ATP.

Some ADP will turn into ATP.

Maybe we have some-- and not
maybe, this is what happens--

some FAD gets-- let me write
it this way-- some FAD gets

oxidized into FADH2.

And the whole reason why we even
pay attention to these,

you might think, hey cellular
respiration is all about ATP.

Why do we even pay attention
to these NADHs and these

FADH2s that get produced
as part of the process?

The reason why we care is that
these are the inputs into the

electron transport chain.

These get oxidized, or they lose
their hydrogens in the

electron transport chain, and
that's where the bulk of the

ATP is actually produced.

And then maybe we'll have
another NAD get reduced, or

gain in hydrogen.

Reduction is gaining
an electron.

Or gaining a hydrogen whose
electron you can hog.

NADH.

And then we end up back
at oxaloacetic acid.

And we can perform the whole
citric acid cycle over again.

So now that we've written it
all out, let's account for

what we have. So depending on--
let me draw some dividing

lines so we know what's what.

So this right here, everything
to the left of that line right

there is glycolysis.

We learned that already.

And then most-- especially
introductory-- textbooks will

give the Krebs cycle credit for
this pyruvate oxidation,

but that's really a
preparatory stage.

The Krebs cycle is really
formally this part where you

start with acetyl-CoA,
you merge it

with oxaloacetic acid.

And then you go and you form
citric acid, which essentially

gets oxidized and produces all
of these things that will need

to either directly produce ATP
or will do it indirectly in

the electron transport chain.

But let's account for everything
that we have. Let's

account for everything
that we have so far.

We already accounted for the
glycolysis right there.

Two net ATPs, two NADHs.

Now, in the citric acid cycle,
or in the Krebs cycle, well

first we have our pyruvate
oxidation.

That produced one NADH.

But remember, if we want to say,
what are we producing for

every glucose?

This is what we produced for
each of the pyruvates.

This NADH was from just
this pyruvate.

But glycolysis produced
two pyruvates.

So everything after this, we're
going to multiply by two

for every molecule of glucose.

So I'll say, for the pyruvate
oxidation times two means that

we got two NADHs.

And then when we look at this
side, the formal Krebs cycle,

what do we get?

We have, how many NADHs?

One, two, three NADHs.

So three NADHs times two,
because we're going to perform

this cycle for each of the
pyruvates produced from

glycolysis.

So that gives us six NADHs.

We have one ATP per
turn of the cycle.

That's going to happen twice.

Once for each pyruvic acid.

So we get two ATPs.

And then we have one FADH2.

But it's good, we're going
to do this cycle twice.

This is per cycle.

So times two.

We have two FADHs.

Now, sometimes in a lot of books
these two NADHs, or per

turn of the Krebs cycle, or per
pyruvate this one NADH,

they'll give credit to the
Krebs cycle for that.

So sometimes instead of having
this intermediate step,

they'll just write four
NADHs right here.

And you'll do it twice.

Once for each puruvate.

So they'll say eight NADHs get
produced from the Krebs cycle.

But the reality is, six from the
Krebs cycle two from the

preparatory stage.

Now the interesting thing is we
can account whether we get

to the 38 ATPs promised by
cellular respiration.

We've directly already produced,
for every molecule

of glucose, two ATPs and
then two more ATPs.

So we have four ATPs.

Four ATPs.

How many NADHs do we have?

2, 4, and then 4 plus 6 10.

We have 10 NADHs.

And then we have 2 FADH2s.

I think in the first
video on cellular

respiration I said FADH.

It should be FADH2, just to be
particular about things.

And these, so you might say,
hey, where are our 38 ATPs?

We only have four
ATPs right now.

But these are actually the
inputs in the electron

transport chain.

These molecules right here get
oxidized in the electron

transport chain.

Every NADH in the electron
transport chain

produces three ATPs.

So these 10 NADHs are going
to produce 30 ATPs in the

electron transport chain.

And each FADH2, when it gets
oxidized and gets turned back

into FAD in the electron
transport chain,

will produce two ATPs.

So two of them are going to
produce four ATPs in the

electron transport chain.

So we now see, we get
four from just what

we've done so far.

Glycolysis, the preparatory
stage and the Krebs or citric

acid cycle.

And then eventually, these
outputs from glycolysis and

the citric acid cycle, when
they get into the electron

transport chain, are going
to produce another 34.

So 34 plus 4, it does get us
to the promised 38 ATP that

you would expect in a
super-efficient cell.

This is kind of your theoretical
maximum.

In most cells they really
don't get quite there.

But this is a good number to
know if you're going to take

the AP bio test or in most
introductory biology courses.

There's one other point
I want to make here.

Everything we've talked about
so far, this is carbohydrate

metabolism.

Or sugar catabolism,
we could call it.

We're breaking down sugars
to produce ATP.

Glucose was our starting
point.

But animals, including us, we
can catabolize other things.

We can catabolize proteins.

We can catabolize fats.

If you have any fat on your
body, you have energy.

In theory, your body should be
able to take that fat and you

should be able to do
things with that.

You should be able
to generate ATP.

And the interesting thing, the
reason why I bring it up here,

is obviously glycolysis is of
no use to these things.

Although fats can be turned
into glucose in the liver.

But the interesting thing is
that the Krebs cycle is the

entry point for these other
catabolic mechanisms. Proteins

can be broken down into amino
acids, which can be broken

down into acetyl-CoA.

Fats can be turned into glucose,
which actually could

then go the whole cellular
respiration.

But the big picture here is
acetyl-CoA is the general

catabolic intermediary that can
then enter the Krebs cycle

and generate ATP regardless
of whether our fuel is

carbohydrates, sugars,
proteins or fats.

Now, we have a good sense of how
everything works out right

now, I think.

Now I'm going to show you a
diagram that you might see in

your biology textbook.

Or I'll actually show you the
actual diagram from Wikipedia.

I just want to show you,
this looks very

daunting and very confusing.

And I think that's why many of
us have trouble with cellular

respiration initially.

Because there's just so
much information.

It's hard to process
what's important.

But I want to just highlight
the important steps here.

Just so you see it's the same
thing that we talked about.

From glycolysis you produce
two pyruvates.

That's the pyruvate
right there.

They actually show its
molecular structure.

This is the pyruvate oxidation
step that I talked about.

The preparatory step.

And you see we produce
a carbon dioxide.

And we reduce NAD
plus into NADH.

Then we're ready to enter
the Krebs cycle.

The acetyl-CoA and the
oxaloacetate or oxaloacetic

acid, they are reacted
together to

create citric acid.

They've actually drawn
the molecule there.

And then the citric acid is
oxidized through the Krebs

cycle right there.

All of these steps, each
of these steps are

facilitated by enzymes.

And it gets oxidized.

But I want to highlight
the interesting parts.

Here we have an NAD get
reduced to NADH.

We have another NAD get
reduced to NADH.

And then over here, another
NAD gets reduced to NADH.

So, so far, if you include the
preparatory step, we've had

four NADHs formed, three
directly from the Krebs cycle.

That's just what I told you.

Now we have, in this diagram
they say GDP.

GTP gets formed from GDP.

The GTP is just guanosine
triphosphate.

It's another purine that can
be a source of energy.

But then that later can be
used to form an ATP.

So this is just the way they
happen to draw it.

But this is the actual ATP
that I drew in the

diagram on the top.

And then they have
this Q group.

And I won't go into it.

And then it gets reduced
over here.

It gets those two hydrogens.

But that essentially ends
up reducing the FADH2s.

So this is where the FADH2
gets produced.

So as promised, we produced,
for each pyruvate that

inputted-- remember, so we're
going to do it twice-- for

each pyruvate we produced one,
two, three, four NADHs.

We produced one ATP
and one FADH2.

That's exactly what
we saw up here.

I'll see you in the
next video.