Regulation of Cellular Respiration Enzymes

8/29/2017 Regulation of cellular respiration (article) | Khan Academy
Regulation of cellularrespiration
How cellular respiration can be sped up or slowed down. Key
enzymes and feedback inhibition.
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Introduction
You can sometimes have too much of a good thing. For instance, consider
ice cream sandwiches. Maybe you really like ice cream sandwiches and buy
a bunch of them at the store. If youre very hungry, that might be a good
choice: you can eat them all quickly, before they melt. If youre only a little
hungry, though, that might be a bad choice: most of the sandwiches will melt
uneaten, at which point you will have wasted some money.
Cells face a related problem when they break down fuels, such as glucose, to
produce ATP. If the cells supply of ATP is low, it would do well to break down
glucose as quickly as possible, replenishing the ATP it needs to keep the
lights on. If the supply of ATP is high, on the other hand, it might not be such
a good idea to oxidize glucose at top speed. ATP is an unstable molecule,
and if it sits around in the cell too long, its likely to spontaneously hydrolyze
back to ADP. This is like the case of the melted ice cream sandwich: the cell
has spent glucose to make ATP, and that ATP ends up going to waste.
Its important for a cell to carefully match the activity of its fuel breakdown
(pathways to its energy needs at a given moment. Here, we'll see how cells
turn cellular respiration pathways up or down in response to ATP levels
and other metabolic signals.
Allosteric enzymes and pathway control

https://www.khanacademy.org/science/biology/cellular-respiration-and-fermentation/variations-on-cellular-respiration/a/regulation-of-cellular-respiration 1/12
How is the activity of a pathway controlled? In many cases, pathways are

regulated through enzymes that catalyze individual steps of the pathway. If
the enzyme for a particular step is active, that step can take place quickly, but
if the enzyme is inactive, the step will happen slowly or not at all. Thus, if a
cell wants to control the activity of a metabolic pathway, it needs to regulate
the activity of one or more of the enzymes in that pathway.
The primary target for regulation a biochemical pathway is often the enzyme
that catalyzes the pathways firstcommitted step(that is, the first step that is
not readily reversible). The concept of a committed step can get a little
complicated when there are many intersecting metabolic pathways, as in
cellular respiration, but this is still a useful idea to keep in mind.
How are the enzymes that control metabolic pathways regulated? A number
cellular respiration enzymes are controlled by the binding of regulatory
molecules at one or more allosteric sites. (Anallosteric siteis just a
regulatory site other than the active site.) Binding of a regulator to the
allosteric site of an enzyme changes its structure, making it more or less
active.
The molecules that bind cellular respiration enzymes act as signals, giving
the enzyme information about the cell's energy state. ATP, ADP, and NADH
are examples of molecules that regulate cellular respiration enzymes. ATP,
for instance, is a "stop" signal: high levels mean that the cell has enough ATP
and does not need to make more through cellular respiration. This is a case
offeedback inhibition, in which a product "feeds back" to shut down its
pathway.
Regulation of glycolysis
Several steps in glycolysis are regulated, but the most important control point
is the third step of the pathway, which is catalyzed by an enzyme
calledphosphofructokinase(PFK). This reaction is the first committed step,
making PFK a central target for regulation of the glycolysis pathway as a
1
whole .
PFK is regulated by ATP, an ADP derivative called AMP, and citrate, as well
as some other molecules we won't discuss here.
ATP.ATP is a negative regulator of PFK, which makes sense: if there is

already plenty of ATP in the cell, glycolysis does not need to make more.
AMP.Adenosine monophosphate (AMP) is a positive regulator of PFK.

When a cell is very low on ATP, it will start squeezing more ATP out of
ADP molecules by converting them to ATP and AMP (ADP +
ADPATP + AMP). High levels of AMP mean that the cell is starved for
2
energy, and that glycolysis must run quickly to replenish ATP .
Citrate.Citrate, the first product of the citric acid cycle, can also inhibit
PFK. If citrate builds up, this is a sign that glycolysis can slow down,
because the citric acid cycle is backed up and doesnt need more fuel.
Pyruvate oxidation
The next key control point comes after glycolysis, when pyruvate is converted
to acetyl CoA. This conversion step is irreversible in many organisms and
3
controls how much acetyl CoA fuel enters the citric acid cycle . The enzyme
that catalyzes the conversion reaction is called pyruvate dehydrogenase.
ATP and NADH make this enzyme less active, while ADP makes it more
active. So, more acetyl CoA is made when energy stores are low.
Pyruvate dehydrogenase is also activated by its substrate, pyruvate, and

inhibited by its product, acetyl CoA. This ensures that acetyl CoA is made
4
only when its needed (and when there's plenty of pyruvate available) .
Citric acid cycle

Entry into the citric acid cycle is largely controlled through pyruvate
dehydrogenase (above), the enzyme that produces acetyl CoA. However,
there are two additional steps in the cycle that are subject to regulation.
These are the two steps in which carbon dioxide molecules are released, and
also the steps at which the first two NADH molecules of the cycle are
produced.
Isocitrate dehydrogenasecontrols the first of these two steps, turning a

six-carbon molecule into a five-carbon molecule. This enzyme is inhibited
by ATP and NADH, but activated by ADP.
-Ketoglutarate dehydrogenasecontrols the second of these two steps,

turning the five-carbon compound from the previous step into a four-
carbon compound bound to CoA (succinyl CoA). This enzyme is inhibited
by ATP, NADH, and several other molecules, including succinyl CoA
itself.
Putting it all together

There are lots of other regulatory mechanisms for cellular respiration besides
the ones we've discussed here. For instance, the speed of the electron
transport chain is regulated by levels of ADP and ATP, and many other
enzymes are subject to regulation. However, these examples give you a feel
for the kind of logic and strategies cells use to regulate metabolic processes.
At each stage, we can see similar elements. For instance, we see feedback
inhibition at many stages, at the level of pathways and of individual reactions.
Monitoring of the cell's energy state through levels of molecules like ATP,
ADP, AMP, and NADH is another common feature.
The diagram below summarizes the key enzymes weve discussed, along
with some of their most important regulators.
[Attribution and references]
Variations on cellular respiration
Lactic acid fermentation
Alcohol or ethanol fermentation
Fermentation and anaerobic respiration
Connections between cellular respiration and other pathways
Regulation of cellular respiration
Practice: Fermentation and anaerobic respiration
Ask a question...
Questions Tips & Thanks
So this page and the entire section is on cellular respiration and

how it works but what Im curious is: With all these many tiny
molecules bopping into each other and performing all these
different and variable reactions inside of a tiny cell, how did
biologists / chemists figure this out?
(Hoping for a detailed technical answer)

12votes 1 comment Flag 2 years agoby Johanna
You can follow up through reading his paper on

it.http://www.nobelprize.org/nobel_prizes/medicine/laureates/
1953/krebs-lecture.pdf
11votes Comment Flag about a year agoby saif Fiaz
Show all 3 answers Answer this question
Can someone tell me if cellular respiration is similar to

photosynthesis?
1vote Comment Flag 2 years agoby tmollman
If anything I would say they are both close to being opposite of

one another. Cellular respiration takes in carbohydrates for
example and break them down to their oxidized form CO2 and
harvest the energy stored in the carbs by breaking their bonds
to drive our physiological functions (Catabolism).
Photosynthesis on the other hand is the process of creating
chemical energy from light energy emitted from the sun. In
plants another process known as the Calvin cycles uses this
chemical energy to(more)
10votes 7 comments Flag 2 years agoby Laurent
Answer this question...
In this entire Cellular Respiration section, I haven't been able to

figure this out: If the anaerobic glycolysis occurs, does pyruvate
oxidation and the krebs cycle continue? Or are the last 3 steps only
able to occur with aerobic glycolysis?
2votes Comment Flag 12 months agoby BriannaDene123
If anaerobic glycolysis occurs, pyruvate oxidation and the

Krebs cycle does not occur. The lactate produced is
transported to the liver where it is converted to pyruvate again.
3votes 1 comment Flag 12 months agoby Ryan D'souza
Why is it essential that the enzymes that catalyze steps 1 and 2

are not inhibited when ATP concentrations are high?
2votes Comment Flag 7 months agoby Cassie Schiller
In all the steps involved in Krebs cycle which are regulated and
which are not and why?
2votes Comment Flag 3 months agoby Ann Laubstein
I thought ADP was too stable to lose another phosphate group. So,
does the cell mistakenly use ADP in place of ATP when it's low on
the latter?
1vote Comment Flag 9 months agoby jrtf2001
ATP is the most common energy carrier for the cell. Each
phosphate that you remove conveys energy but less each
level. ATP has more energy than ADP for example. The cell
sometimes doesn't need all the energy from ATP -> ADP and
thus, ADP -> AMP can be used to drive a reaction. This is why
the cell might use ADP. Our enzymes are pretty good at
choosing the right energy carrier that leads to the best
efficiencies. ADP usually doesn't carry enough energy to
power a reaction requiring ATP.
2votes 1 comment Flag 7 months agoby Don Zhu
If the Acetyl-CoA wasn't functional in a plant cell, what would the

specific outcome be?
1vote Comment Flag 5 months agoby Marisa
how does citrate come out of the mitochondria ?

1vote Comment Flag 5 months agoby siddhiad
Why can't cells in anaerobic conditions enter the Krebs cycle? I

didn't see any mention of oxygen playing a role in this process?
1vote Comment Flag 26 days agoby jgingold533
Because the Krebs cycle needs NAD+, NAD+ is generated by

the electron transport chain and the transport chain requires
oxygen. Thus if the transport chain stops because of
anaerobic condition, no NAD+ is generated = Krebs cycle

cannot happen.

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8/29/2017 Regulation of cellular respiration (article) | Khan Academy

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Allosteric enzymes and pathway control

How is the activity of a pathway controlled? In many cases, pathways are

ATP.ATP is a negative regulator of PFK, which makes sense: if there is

AMP.Adenosine monophosphate (AMP) is a positive regulator of PFK.

Pyruvate dehydrogenase is also activated by its substrate, pyruvate, and

Citric acid cycle

Isocitrate dehydrogenasecontrols the first of these two steps, turning a

-Ketoglutarate dehydrogenasecontrols the second of these two steps,

Putting it all together

[Attribution and references]

Variations on cellular respiration

Lactic acid fermentation

Alcohol or ethanol fermentation

Fermentation and anaerobic respiration

Connections between cellular respiration and other pathways

Regulation of cellular respiration

Practice: Fermentation and anaerobic respiration

Questions Tips & Thanks

So this page and the entire section is on cellular respiration and

(Hoping for a detailed technical answer)

You can follow up through reading his paper on

Show all 3 answers Answer this question

Can someone tell me if cellular respiration is similar to

If anything I would say they are both close to being opposite of

Answer this question...

In this entire Cellular Respiration section, I haven't been able to

If anaerobic glycolysis occurs, pyruvate oxidation and the

Answer this question...

Why is it essential that the enzymes that catalyze steps 1 and 2

Answer this question...

Answer this question...

Answer this question...

If the Acetyl-CoA wasn't functional in a plant cell, what would the

Answer this question...

how does citrate come out of the mitochondria ?

Answer this question...

Why can't cells in anaerobic conditions enter the Krebs cycle? I

Because the Krebs cycle needs NAD+, NAD+ is generated by

anaerobic condition, no NAD+ is generated = Krebs cycle

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