- [Voiceover] When talking
about carbohydrate metabolism
we can't forget to mention the
pentose phosphate pathways.
So, where does the pentose
phosphate pathway fit into
the breakdown of glucose?
So, let's go ahead and review
the breakdown of glucose
as we normally kind of
usually conceive of it as.
So, we go ahead and
start out with glucose,
which I'm drawing here
to symbolize it with
a six-carbon sugar backbone.
And we usually imagine that
glucose begins to be broken down
in the cytosol of the cell through
a series of reactions
that we call glycolysis.
And then, of course, it
goes through the Krebs cycle
in the mitochondria, also
known as the TCA cycle.
And then, finally, it goes to
the electron transport chain
in the mitochondria to produce ATP.
So, that's kind of usually
the end product we think of
when we think about breaking down glucose.
But, the pentose phosphate pathway
is kind of a unique pathway,
because it turns out
that in this pathway no ATP
is consumed or produced.
That's kind of unique, to point out.
So, where does it fit in
to this overall pathway?
It turns out that the
linear way I've written
cellular respiration is
actually only partly true.
It's a great way to conceptualize it,
but there are many branches
or kind of side reactions
that are taking place
almost simultaneously
with the breakdown of glucose,
and the pentose phosphate
pathway is one of these.
So, turns out that as glucose begins
to go through glycolysis,
some of it is shunted away
to become the pentose phosphate pathway.
So, glucose continues to be broken down,
but it continues to be broken down
to produce different
products than it would
if it continued through
going through glycolysis,
and Krebs, and then to the
electron transport chain.
So, as you can see, I've written
pentose phosphate pathway
kind of suggestively by
highlighting pentose and phosphate
in different colors to point out to you
that there are two primary
products in this pathway.
So, the first is the production
of a five-carbon pentose sugar.
So, pentose is just another
word for five-carbon sugar,
and the particular name of this sugar
is ribose-five-phosphate.
And this sugar, so it's
a five-carbon sugar,
I'll go ahead and draw
that to remind us of that,
is an important substrate
in producing DNA and RNA.
So, if you remember, DNA
and RNA contain nucleotides,
and the nucleotides
contain a nitrogenous base,
a phosphate group, and
a five-carbon sugar.
So, in the case of DNA, it's deoxyribose,
and in RNA, it's just ribose.
But, in either case, this
ribose-five-phosphate
is an important precursor
to creating DNA and RNA,
so, quite a crucial molecule.
Now, the second primary
product of this reaction,
as this phosphate nicely implies,
is a phosphorylated molecule
that is usually abbreviated
as N-A-D-P, P standing of
course for the phosphate
in this molecule, H.
NADPH.
So, this is not to be
confused with the NADH, which,
if you recall, I'll go ahead
and actually draw that in here,
if you recall, NADH is actually produced
in cellular respiration during
the breakdown of glucose.
So, this produces NADH,
which, of course, contributes
electrons to the electron transport chain.
So, of course, the question
you might have in your mind
is how is NADH different from
the easily confused NADPH,
because they sound like similar molecules,
and in many ways they are.
So, they actually both exist
in pairs inside the cell,
so, NAD-plus we know is
inter-converted with NADH,
and NADP-plus is
inter-converted with NADPH.
So, of course, the H
forms of these molecules
are the reduced form of these molecules,
and the plus, or oxidized
form of these molecules,
are the NAD-plus and NADP-plus.
But, what's different about
these two pairs of molecules
is the relative amount of the reduced form
and the oxidized form inside the cell.
So, just to give you a sense of that,
the ratio of NAD-plus
to NADH is about 1000.
In other words, if you
took the amount of NAD-plus
and divided it by the
amount of NADH in the body,
you would have about
1000 times more NAD-plus.
On the other hand, if you
took the amount of NADP-plus
divided by the amount of
NADPH, you would get 0.1.
So, essentially what this
is telling us is that
there is a lot of NAD-plus in the body
and a lot of NADPH in
the body, but not much
of NADH or NADP-plus.
And, knowing this
actually helps me remember
and differentiate between the role
of NADH and NADPH inside the body.
So, first, I reason out
to myself that if there's
a lot of NAD-plus present in the body,
most of the NAD-plus will
want to accept electrons.
And, of course, the biggest
role in accepting electrons
comes in the breakdown of glucose
and producing NADH, so that makes sense.
On the other hand, the
primary role of NADPH,
which is what we have the majority of,
is to donate electrons,
so I'm gonna go ahead
and write that here.
So, the biggest role of NADPH in the body
is to donate electrons, and that,
of course, would not be very helpful
in breaking down glucose, right?
Because, the breakdown of
glucose donates electrons,
it doesn't accept them.
Now, I will remind you
that donating electrons
is really important in anabolic reaction.
So, remember that
anabolic reactions involve
building up molecules,
such as in the synthesis
of fatty acids, for example.
And so, NADPH plays a
vital role in kind of
providing this reducing power, so to say,
for these anabolic reactions.
In addition, I'll briefly
mention that NADPH
also uses its reducing power, its ability
to donate electrons, to maintain the store
of antioxidants inside the body.
So, you know, kind of an ironic part about
having oxygen as a requirement
for cellular respiration
is that some of this oxygen
can become really reactive
if it gains an extra electron.
And so, the goal of kind
of some of the molecules
in your body are to serve as antioxidants
to kind of trap these
reactive oxygen species
from reacting with important
things in your body,
like DNA or proteins.
And so, once they do that, of course,
some of these antioxidant molecules,
in the process of reacting
with a reactive electron-rich
oxygen molecule become oxidized.
And so, of course, NADPH
can come in and save the day
by donating electrons to
reduce the oxidized form
of these antioxidants back
into their reduced form
so that they can again react with
any rogue reactive oxygen species.
Alright, so now we're ready to look
at the pentose phosphate
pathway in more detail.
So, I'm going to go ahead
and bring up a diagram
of how the pentose phosphate
pathway is usually represented
in most textbooks, and this is
a lot of detail, admittedly.
And, I don't want you to
get lost in the details,
so I'm going to try and break it down
and hone your attention to the
most important details
to take away from this.
So, the first of these important details
is to note that there are two big phases
of the pentose phosphate pathway.
So, the first is called
the oxidative phase
and the second is called
the non-oxidative phase.
And, you know, as the name implies,
oxidative phase we're oxidizing.
So, remember that breakdown of glucose,
breakdown of carbohydrates,
is an oxidative process in general.
And, in this phase, the
big idea here is that
we are producing NADPH, so that is
the big product of the oxidative phase.
So, we actually start out with
glucose-six-phosphate here.
So, just note that we start
off with this molecule here,
which I'll remind you is
one of the first metabolites
that's produced in glycolysis.
So, this is essentially
shunted from glycolysis,
which, of course, starts out with glucose.
So, glucose enters
glycolysis and some of it
will continue through
cellular respiration,
but the other part of the
glucose will then be shunted
through this glucose-six-phosphate into
the oxidative phase of the
pentose phosphate pathway.
And, glucose-six-phosphate
is then broken down
in a series of steps which
aren't entirely important,
but the key idea here is that
you're producing NADPH along the way.
Now, the non-oxidative
phase starts with this
molecule called ribulose-five-phosphate,
and it's really not
important to know except
the fact that it kind of sounds
like ribose-five-phosphate,
right, which I mentioned before was one of
the main primary products of
the pentose phosphate pathway
and indeed, it's a precursor
for the ribose-five-phosphate.
So, let's see how that happens.
Let's go ahead and scroll down here.
So, ribulose-five-phosphate
is actually broken down
by an enzyme, an isomerase.
So, it's essentially
switching around the molecule.
It's not really changing
the chemical formula,
but it's switching around the structure
to ribose-five-phosphate.
So, that's key.
So,remember that's one
of our main products
of the pentose phosphate pathway.
So, another key point of
the non-oxidative phase,
so we produce, of course,
ribose-five-phosphate.
Another key point here
is that we're also able
to interconvert various sugars,
so interconvert sugars.
And why is this important?
This turns out to be
really handy for the cell,
because notice here that
there are some products,
like fructose-six-phosphate
and glyceraldehyde-three-phosphate
and fructose-six-phosphate
that you might be familiar with
that come from glycolysis.
And, remember that these are
not all five-carbon sugars,
right, you know that
glyceraldehyde-three-phosphate
is actually a three-carbon sugar.
So, the ability to interconvert
sugars through enzymes
like the transaldolase
and the transketolase
will essentially allow cells to produce
more ribose-five-phosphate for DNA
and RNA synthesis if needed.
And, we do want to say
this with one caveat
which is although the
glycolytic intermediates
can be reinter-converted
into ribose-five-phosphate,
they cannot go all the way up the pathway
to glucose-six-phosphate.
So, these oxidative phase
reactions are irreversible.
So, shown by kind of the
unidirectional arrow,
but the non-oxidative phase, of course,
allows interconversion and
hence is kind of thought of
as more of a reversible pathway.
So, that, in a nutshell, is
the pentose phosphate pathway,
and I'll return to the kind
of main slide at the beginning
and just remind you that the key takeaway
is that we are producing
a pentose sugar, ribose,
and a phosphorylated molecule,
NADPH, in this pathway,
and that the most unique
part of this pathway
is that even though we classify it
as part of carbohydrate metabolism
because it utilizes the metabolites from
the breakdown of glucose,
there's no ATP consumed
or produced in this cycle, so that's
what makes the pentose
phosphate pathway unique.
