Transcript Metabolism part 2 - Krebs cycle and electron transport

Metabolism Part 2:
Krebs cycle
This tutorial will take you through the
basics of the Krebs cycle
for SC 120
Click this button to move forward
What was the first stage of
metabolism?
Sorry – anabolism is
when your cell builds
large molecules
like
Anabolism
proteins.
Sorry – catabolism
refers to breaking
Catabolism
down cell
molecules
to get energy from
them
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RIGHT!
‘Glyco’Glycolysis
= sugar
‘lysis’ = breaking
‘Gluco’ = sugar
‘genesis’ = making
Glucogenesis
Does your cell MAKE
sugar in the first step of
metabolism?
Where did glycolysis take place?
Mitochondria can’t
cope with sugar
molecules.
They need
Mitochondria
smaller molecules.
Sorry – the nucleus is
where your DNA is stored.
Your cell doesn’t
do much
Nucleus
breaking down of things in
there – it might damage
the DNA!
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Ribosomes are
involved in creating
Ribosomes
protein
– not in
breaking anything
down
Right! As soon as glucose
crosses the cell
membrane
and enters the
Cytoplasm
cytoplasm, the glycolysis
enzymes grab it.
What does glycolysis break
glucose into?
Right! Glycolysis
breaks a 6-carbon
glucose
into two
32 Pyruvic
acids
carbon pyruvic acids.
Glycolysis doesn’t
break
glucose
down
Carbon
dioxide
that far.
and water
Glycolysis takes off 2
pairs of electrons, but
pairs
of
there is a2lot
more than
electronselectrons
to a glucose
molecule.
Glucose already is a
sugar.
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Sugar
Here’s a summary of glycolysis
One molecule of
glucose
Two molecules of
pyruvic acid
(6 carbons)
(3 carbons each)
Energy released!!
Net gain of 2
ATPs
AND – 4
electrons are
removed
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Handed to 2
molecules
of NAD
Glycolysis was the first step.
• It broke the glucose into pyruvic acids.
• Now, those pyruvic acids will be
passed into the mitochondria to be
broken down further.
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The glycolysis tutorial used a
cooking metaphor.
Energy
released!!
• Remember this guy?
• Now he’s handing those pyruvic acids on to
another set of enzymes.
Clip art from Microsoft
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Inside the mitochondria…
• A whole group of enzymes is waiting.
• These make up the KREBS CYCLE.
• They will pass the pyruvic acid
molecules along
the line, gradually
breaking them down
to release energy,
which they can use to make ATP.
Clip art from Microsoft
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The first step in the process is to
take the pyruvic acid into the
mitochondria.
• This is done by a molecule called
Coenzyme A.
Clip art from Microsoft
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Coenzyme A
• Coenzyme A doesn’t just carry pyruvic
acid.
• It also modifies it, by taking a carbon
off the end of it.
• The Krebs Cycle enzymes will only
accept 2-carbon compounds.
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Removing a carbon also involves
removing 2 electrons
One molecule of
pyruvic acid
One acetyl
molecule
(3 carbons)
(2 carbons )
One carbon is
lost as CO2
AND – 2
electrons are
removed
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Handed to a
molecule of
NAD
What’s NAD?
That’s right! NAD and
FAD are used to hold
An electron
electrons, so the
electronscarrier
can’t
damage the cell.
Organelles are really large
compared to the
A cell we’re
organelle
molecules
dealing
with.
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NAD isn’t made
during cell
A product of
respiration. It’s
Cellfor
respiration
needed
cell
respiration.
NAD isn’t a sugar. It’s
actually more like the
A sugar molecule
compounds
that make
up DNA.
The 2-carbon molecule is passed
to the Krebs cycle enzymes
• They pass it along and break it into two
CO2 molecules
Clip art from Microsoft
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Glucose
Pyruvic
acid
Acetyl
molecule
What about ATP?
• The glycolysis pathway
made 2 ATPs when it broke
glucose.
•The Krebs cycle makes
another ATP for every acetyl
molecule it breaks down.
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Two CO2
molecules
Glucose
ATP
Pyruvic
acid
ATP
Acetyl
molecule
ATP
Two CO2
molecules
from each
acetyl
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Glucose
Pyruvic
acid
For every glucose you eat,
you get:
ATP
• 2 ATPs from glycolysis
ATP
• 2 acetyl molecules  2 more ATP
ATPs from the Krebs cycle.
ATP
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Acetyl
molecule
Two CO2
molecules
from each
acetyl
Acetyl
molecule
AND electrons are taken off in
the Krebs cycle:
For every acetyl molecule
• 3 pairs of high-energy
electrons  handed to NAD
Two CO2
molecules
from each
acetyl
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• 1 pair of lower-energy
electrons  handed to FAD
When a pair of electrons is handed
to NAD, what happens?
Right! Remember GER:
Gain of Electrons is
NAD is reduced
Reduction.
Remember LEO: Loss of
Electrons is Oxidation.
NAD is oxidized
Did the NAD lose
electrons?
Remember GER: Gain of
Electrons is Reduction.
Acetyl
is reduced
Did the
acetyl
molecule
CO2 was formed, but not
by handing electrons to
CO2 is produced
NAD.
gain or lose electrons?
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Let’s review metabolism so far.
Which pathway breaks glucose into
pyruvic acids?
‘gluco’ = glucose
‘genesis’
= creation
Glucogenesis
So this would be making
glucose, not breaking it!
The Krebs cycle can’t
use glucose. It will only
metabolize
2-carbon
Krebs
cycle
compounds.
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Right! Glycolysis does
the initial breakdown of
sugar. Glycolysis
Sorry, Coenzyme A is the
messenger that carries
Coenzyme Aglucose
the broken-down
into the Krebs cycle.
Redo Questions
How many carbons does a glucose
molecule have?
sorry, that’s too small!
2
Sorry, that’s too small!
4
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Right! Glucose is
C6H12O6.
6
Sorry, that’s too big!
8
Redo Questions
How many carbons does a pyruvic acid
molecule have?
sorry, that’s too small!
2
That’s right! When you
split a 6-carbon glucose
in half, you get
3 two 3carbon pyruvic acids.
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That’s too big – if you
broke glucose in half,
4 two 4would you get
carbon compounds?
The glucose only had 6
carbons! So if you broke
6 still end up
it, would you
with 6-carbon
compounds?
Redo Questions
How many net ATPs did glycolysis
make?
That’s right!
2
Sorry – recheck the
pathway.
3
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Glycolysis did make 4
ATPs, but it used 2. So
4 net GAIN
what was the
in ATPs?
We wish! Glycolysis is
just not efficient enough
to make this6 many ATPs.
Redo Questions
How can the pyruvic acids get to the
Krebs cycle for further breakdown?
Sorry – the nucleus
Coenzyme
A takes
doesn’t
break down
themso there
pyruvic acids,
the
nucleus
is nointo
point
taking
them
in there.
The problem with this
Electron
carriers
answer
is that
electron
take them
the
carriers
carry into
electrons,
mitochondrion
not pyruvic
acids.
Right!
Coenzyme A takes
them into the
mitochondrion
There are two problems with
this. FAD
First, takes
FAD is them
an electron
carrier and
can’t
carry pyruvic
into
the
acids. Second, the pyruvic
acids arecytoplasm
already in the
cytoplasm!
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Redo Questions
What happens to pyruvic acids on the
way into the mitochondria?
This isn’t quite right.
Coenzyme
A breaks
Coenzyme
A can’t
them down
completely
breakinto
down
CO2
pyruvic acids.
If glycolysis could do
this,
the pyruvic
acids
Glycolysis
enzymes
wouldn’t
needinto
to go
into
break them
CO
2
the mitochondria.
Right! The Krebs cycle likes
2-carbon compounds, so
Coenzyme
A breaks
a carbon
Coenzyme
A breaks
off each
one pyruvic
carbonacid.
off them
This can happen, but it
only
happens
if there
They
are turned
intois
no Oxygen
the cell
Lacticand
acids
cannot run the Krebs
cycle.
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Redo Questions
When a carbon is taken off the pyruvic
acids, what are they called?
Sorry – Coenzyme A is
the molecule that carries
them. Coenzyme A
Sorry – lactic acid is a 3carbon compound made
Lactic acid
when electrons
are
handed to pyruvic acid.
Glycogen would be a
molecule that made
glucose.Glycogen
These little
molecules are made
FROM glucose.
Right! The two-carbon
group is an acetyl
Acetyl
group. When
Coenzyme
A is carrying one, we call
it acetyl CoA.
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Redo Questions
What do the Krebs cycle enzymes do
to the acetyl molecule?
Sorry – this is what
happensReduce
to pyruvic
it, acid
if it CAN’T
the
formingenter
lactic
acid
Krebs cycle
That’s right! The Krebs
Break
it down
into
cycle
breaks
the acetyl
two molecules
molecule
down and the
of CO2
CO2 is exhaled.
Sorry- the whole
process is aimed at
Put them
together
breaking
glucose
down,
to make glucose
not forming it.
That would not make much
sense, after Coenzyme A did
Pass
all that
workittoback
moveto
it from
the cytoplasm
into the
the cytoplasm
mitochondria.
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Redo Questions
How many ATPs will the Krebs cycle make
when it breaks down one acetyl molecule?
Right!
1
Sorry- the Krebs cycle is
not this efficient.
2
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Sorry- the Krebs cycle is
not this efficient.
3
Sorry- the Krebs cycle is
not this efficient.
4
Redo Questions
Glucose
Pyruvic
acid
For every glucose you eat,
you get:
ATP
• 2 ATPs from glycolysis
ATP
• 2 acetyl molecules  2 more ATP
ATPs from the Krebs cycle.
ATP
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Acetyl
molecule
Two CO2
molecules
from each
acetyl
Four ATPs? You went through all
that for four measly ATPs?
• That’s not enough ATPs to keep you alive.
• When scientists studied the actual amount
of ATP cells got from a glucose, they
found the cells got way more than 4.
• Cells get more like 36 ATPs from one
glucose molecule. How are they doing it?
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The review quiz left something out.
•
•
•
•
It asked about glycolysis
And about the Krebs cycle
And about coenzyme A
And about pyruvic acids and acetyl
molecules
• But it didn’t mention ELECTRONS.
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Every time a molecule was broken,
electrons were removed.
• Electrons were removed during glycolysis
• And by Coenzyme A
• And by the Krebs cycle
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Glucose
Pyruvic
acid
Acetyl
molecule
Glycolysis removed 2 pairs of
electrons
Then Acetyl CoA removed
another pair from each pyruvic
acid
And the Krebs cycle took 4 more
pairs off each acetyl group
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Two CO2
molecules
from each
acetyl
So all in all:
Glucose
Pyruvic
acid
Acetyl
CO2
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12 pairs of
electrons were
removed as the
glucose was
broken down.
Pyruvic
acid
Acetyl
CO2
Where did all those electrons go?
That would be really
bad. The electrons
Into
the nucleus
would
damage
the DNA
and mutate the cell.
Sorry- there’s not an
easy way to exhale
They were exhaled
electrons.
This would cause
damage to the blood
vessels.
Into the blood
Right! Remember NAD
and FAD, Onto
the electron
carriers?
electron carriers
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So all in all:
Glucose
Pyruvic
acid
Acetyl
CO2
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10 pairs of
electrons were
given to NAD
2 pairs were given
to FAD
Pyruvic
acid
Acetyl
CO2
By the end of the Krebs cycle, you
have:
10 NADs filled with electrons …
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and two FADs filled with electrons.
How would you describe this?
The glucose has been
brokenThe
down
– but it has
glucose
lost has
electrons.
been reduced
Remember LEO: Loss of
Electrons is Oxidation.
That’s right! Gain of
Electrons
is Reduction
The NADs
and FADs –
thehave
NADs
andreduced
FADs
been
have gained electrons.
The pyruvic acid has been
broken down – but it has lost
electrons.
LEO:
The Remember
pyruvic acid
Losshas
of Electrons
is
been reduced
Oxidation.
Remember LEO: Loss of
Electrons is Oxidation. The
Theand
NADs
and
FADs
NADs
FADs
have
GAINED
electrons,
so they
haven’t
have been
oxidized
been oxidized.
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The mitochondrion is like one bag
inside another.
This is the outer space of the mitochondrion
This is the inner space of the mitochondrion,
where the Krebs cycle enzymes are.
This is the inner mitochondrial membrane
This is the outer mitochondrial membrane
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After the Krebs cycle has been
running a while…
The inner space of the mitochondrion is full of reduced NADs and FADs.
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And buzzing around all those
electrons …
•
Are swarms of H+ ions. What a mess!
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When your electron carriers are
full, metabolism must stop.
•
Then the cell won’t be able to make any more ATP, and it will die.
‘
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Something has to take out the
trash.
• This is a job for OXYGEN!
• An Oxygen atom can pick up two
electrons, and then two H+ will follow the
electrons.
O + 2 e- + 2 H+  H2O
Clip art from Microsoft
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O+2
e
+2
+
H
 H2O
• Oxygen is your cell’s janitor.
• It takes the dangerous electrons and H+
ions and carries them out as harmless
water.
• This is the reason you need Oxygen to
live.
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Some cells can live without Oxygen
• They have to use some other molecule as
a ‘janitor.’
• For instance, some cells use Sulfur, and
they produce H2S when the sulfur carries
the electrons and H+ ions out.
• The next time you wade in a muddy pond,
see if you can smell the H2S made by
these cells.
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Humans can only use Oxygen to
carry out the electrons and H+ ions.
• We are obligate aerobes.
• ‘Obligate’ means obliged – we have no
choice.
• ‘Aerobes’ means Oxygen users.
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All this has explained why we need
Oxygen,
• But not where those extra 32 ATPs are
made.
• They are made in the process of loading
up the Oxygen with the electrons and H+
ions.
• Let’s look back inside the mitochondrion…
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Here’s our mitochondrion , full of
reduced electron carriers and H+ ions.
•
Click here
to zoom in
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Inner space of mitochondrion – this is where the
Reduced electron carriers and the H+ ions
are
Outer space of mitochondrion is separated from the
inner space by a semi-permeable membrane.
The reduced electron carriers and
H+ ions cannot diffuse through that membrane,
so they must stay in the inner space – unless a protein lets them
cross.
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Inner space of mitochondrion – this is where the
Reduced electron carriers and the H+ ions
are
These are proteins in the membrane – the cytochromes.
They can let electrons and H+ ions through.
This set of proteins is called the ELECTRON TRANSPORT CHAIN.
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The reduced NAD dumps its electrons into one of the cytochromes.
Now it can go back and do its job,
picking up new electrons.
The H+ ions stay right here, though.
They were never interested in the NAD – only in its electrons.
So now, they want to hang around the cytochrome that has the electrons.
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The cytochrome’s job is to let the electrons and H+ through the membrane.
Click on the first cytochrome to see it do its thing.
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See that again
The thing is - the cytochrome lets electrons go
both ways across the membrane,
but H+ ions can only go one way.
Click on the first cytochrome again to see what this means.
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See that again
Now two of the H+ ions are stuck in the outer region of the mitochondrion.
But the two electrons have gone back inside –
to be handed to the next cytochrome.
Click on the second cytochrome to see it do its thing.
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See that again
By now, I’m sure you know what the third cytochrome will do!
Click on the third cytochrome to see it do its thing
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See it all again
There’s only one protein in the membrane
that will let the H+ ions back through – ATP synthase.
It takes the energy from the H+ ions and uses it to make ATP.
ATP
ATP
synthase
Click on the ATP synthase to see it do its thing.
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See that again
ATP
Now Oxygen picks up
the electrons and the H+ ions
and carries them out of the cell.
ATP
synthase
Click on Oxygen to see him do his thing
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See that again
Since three pairs of H+ ions followed
the electrons across the membrane, the ATP synthase
will make 3 ATPs from letting them back in.
ATP
ATP
ATP
ATP
synthase
Click on the ATP synthase to see it do its thing.
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See it all again
The reduced NAD dumps its electrons into the first cytochrome,
so they go back and forth three times
and lure 3 pairs of H+ across the membrane,
which make 3 ATPs coming back in.
Reduced FAD has less energy,
and can only hand its electrons to the second cytochrome.
They only cross the membrane twice
and lure 2 pairs of H+ across,
so only 2 ATP are made
when the H+ go back across the membrane.
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From metabolizing one molecule of
glucose,
Your cell produced 10 reduced NADs and 2 reduced FADs.
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How many ATPs will they make?
10 reduced NADs = 30 ATPs …
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and two reduced FADs = 4 ATPs.
So all in all:
Glucose
Pyruvic
acid
Acetyl
Glycolysis made 2
ATP
The KREBS cycle
made 2 ATP
10 reduced NAD = 30
ATP
Pyruvic
acid
Acetyl
2 reduced FAD = 4
ATP
CO2
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The total is 38 ATP
CO2
Where is the Krebs cycle located?
Sorry – that’s where
glycolysis is.
In the cytoplasm
No, it’s inside an
organelle.
On the
You’re close, but not
quite right.
In the outer space
of the mitochondrion
Right!
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cell membrane
In the inner space
of the mitochondrion
Where is the electron transport chain
located?
Sorry – since it uses lots
of reduced NAD and FAD
the
cytoplasm
from In
the
Krebs
cycle, it’s
in the same place as the
Krebs cycle.
It’s on a membrane, but
not the cell
Onmembrane.
the
Sorry- the endoplasmic
reticulum is for making
In the endoplasmic
proteins.
reticulum
Right! It is in the inner
membrane of the
In the mitochondria
mitochondrion.
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cell membrane
Redo Questions
What are the proteins in the electron chain
called?
Right!
cytochromes
Sorry- chromatids are
single copies of a
chromosome
chromatids
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Sorry- chromosomes are
the packages of DNA in
chromosomes
your cell’s
nucleus.
Cytoplasm is the material
filling the cell.
cytoplasm
Redo Questions
What do those proteins do?
The electrons were
Move
electrons
already
in the
inner
into the inner space
space!
of the mitochondrion
Right!
This is partly true, but
they do
more.
Move
electrons
into the outer space
of the mitochondrion
The electrons were
Move electrons to
already
thespace
inner
thein
inner
space!and then back
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Move electrons to
the outer space
and then back
to the inner space
to the outer space
Redo Questions
What do H+ ions do?
They were already in the
Move
inner space!
into the inner space
of the mitochondrion
Not quite. The electrons
Move to
can move
back in
the outer space
through
the
and
then back
cytochromes,
the H+
to the innerbut
space
ions can’t.
That’s right! They follow
the electrons
into the
Move
outer
intospace.
the outer space
of the mitochondrion
They were already in the
Move to
inner the
space!
inner space
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and then back
to the outer space
Redo Questions
How does the electron transport chain make
ATP?
That’s what glycolysis
dies, not the electron
By breaking
transport
chain.glucose
That’s right! The energy
fromH+
theions
H+pass
ionsback
is used
into the
inner space
to make
ATP.
The electron transport
chain doesn’t have any
enzymes
for breaking
By breaking
fats
things.
Not quite -- it’s not
electrons
the
Electronsthat
passrun
through
enzyme.
an ATP-producing enzyme
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through the ATP synthase
Redo Questions
How many ATPs do the electrons from one
reduced NAD make?
It’s more than that! How
many times do they go
1
across the inner
mitochondrial
membrane?
That’s right!
It’s more than that! How
many times do they go
across the inner
2
mitochondrial
membrane?
It’s less than that! How
many times do they go
4
across the inner
mitochondrial
membrane?
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3
Redo Questions
How many ATPs do the electrons from one
reduced FAD make?
It’s more than that! How
many times do they go
1
across the inner
mitochondrial
membrane?
It’s less than that! How
many times do they go
3
across the inner
mitochondrial
membrane?
That’s right!
It’s less than that! How
many times do they go
4
across the inner
mitochondrial
membrane?
2
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Redo Questions
How many ATPs do you get from the
electron transport chain when you
metabolize one molecule of glucose?
This is the number of
reduced NAD that send
10
electrons through
the
electron transport chain
That’s the total number
of ATPs made in
38 the
glycolysis plus
Krebs cycle plus the
electron transport chain.
That’s the number of
ATPs you make in
glycolysis, or
2 in the
Krebs cycle.
That’s right! 30 from the
10 reduced NADs, and 4
34
from the 2 reduced
FADs.
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Redo Questions
This only leaves one question. If you remember, I
said cells made 36 ATP from a molecule of glucose.
Glucose
Pyruvic
acid
Acetyl
Glycolysis made 2
ATP
The KREBS cycle
made 2 ATP
10 reduced NAD = 30
ATP
Pyruvic
acid
Acetyl
2 reduced FAD = 4
ATP
CO2
The total is 38 ATP
So why did I say
36?
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CO2
Glucose
Pyruvic
acid
Acetyl
CO2
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The answer is these
pairs of electrons.
They were removed
from glucose and
pyruvic acid
OUTSIDE the
mitochondria!
Pyruvic
acid
Acetyl
CO2
Glucose
Pyruvic
acid
Acetyl
CO2
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These electrons were
handed to NAD, but
the NAD was in the
wrong place. It took
2 ATPs to move that
reduced NAD into
the mitochondria, so
it could pass its
electrons to the
electron transport
chain.
Pyruvic
acid
Acetyl
CO2
Glucose
Pyruvic
acid
Acetyl
Glycolysis made 2
ATP
The KREBS cycle
made 2 ATP
10 reduced NAD = 30
ATP
Pyruvic
acid
Acetyl
2 reduced FAD = 4
ATP
CO2
Minus 2 used to
move the NAD
TOTAL = 36 ATP per
glucose
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CO2
This is the end of the metabolism
tutorial.
• Here’s a question to work on at home:
• Any kind of food can be broken down into
2-carbon chunks and used by the Krebs
cycle.
• How much ATP would you get if you ate a
16-carbon fatty acid and broke it into 2carbon chunks and fed it into the Krebs
cycle?
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