Regulation Of Glycolysis Flashcards

1
Q

Describe glucose

A

Glucose is polar and tiny.
It’s happy in the blood.

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2
Q

Where does glucose go if it can’t get into the cell?

A

If the glucose does not get into cells, it’ll go to the kidney. This isn’t good because it’s too big. You don’t want glucose in your urine.

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3
Q

Where does glycolysis take place?

A

Glycolysis takes place within the cytoplasm, immediately inside the cell

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4
Q

What happens when glucose approaches the outside of a cell?

A

Glucose will approach the membrane, get through the outside but repelled through the non-polar environment!

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5
Q

What does glucose need to enter the cell? And why can’t it go in by itself?

A

GLUT 1 - glucose transport proteins. These are tunnels to provide an opening for the size or glucose that is polar to pass through the membrane

GLUT moves to the cell surface

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6
Q

What happens to glucose when it’s in the cytosol?
Which enzyme acts on it?
Turns it into?

A

In the cytosol hexokinase acts on glucose and adds a phosphate (phosphorylates it) and turns it into G6P and now it has a negative charge

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7
Q

Describe the entry/exit for the GLUT transport protein

A

Entry and exit of the GLUT transport proteins contain many E amino acids — negatively charged glutamic acid.

GLUT is a 2-way tunnel.

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8
Q

Structure of GLUT tunnels

A

GLUT tunnels are primarily alpha helices

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9
Q

What happens when glucose enters the cell?

A

Glutamic acid at the entry and exit is negatively charged

Glucose is phosphorylated inside the cell, which is negatively charged

This means it can’t get out because negative and negative repel!

G6P is trapped!

This means the tunnel is still open for more glucose to come in and keep the G6P inside.

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10
Q

How is glucose phosphorylated?

A

if there is no hexokinase in the cell, glucose won’t get phosphorylated, so it can leave

Hexokinase is regulated

Don’t make hexokinase if we don’t want glucose in the cell

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11
Q

What do kinases do?

A

A kinase will put a phosphate on a molecule — the source is ATP

kinase uses ATP to phosphorylate

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12
Q

What needs to be in the active site of hexokinase in order to make G6P?

A

Can’t make G6P unless glucose is in the active site of hexokinase.

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13
Q

Talk about ADP and ATP

A

ATP turns into ADP + Pi

ADP is a lot more stable than ATP.

That third phosphate on ATP will come off if it slams into another molecule

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14
Q

Describe the reaction of glucose to G6P

A

Glucose to G6P reaction is not favourable — but the reaction of ATP to ADP + Pi is favourable and that helps offset reaction 1 (glucose to G6P)

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15
Q

Energy in G6P

A

G6P is less stable than glucose after ATP gave it a phosphate. There is potential energy stored in that G6P molecule

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16
Q

What is happening in steps 7 and 10 of glycolysis?

A

In steps 7 & 10 of glycolysis, we are making ATP.

The energy in 1,3 BPG and PEP have more energy contained in their phosphate than ADP so the phosphate pops off and we get ADP to ATP

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17
Q

Why are there so many steps in glycolysis

A

Energetics —
Regulation —

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18
Q

Which molecule uses ATP

A

Kinase (look for this)
First half generates ATP and the second half uses ATP

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19
Q

What happens after glycolysis?

A

After glycolysis :
If oxygen is present, will use the NADH as an electron transporter and further oxidation

If oxygen is not present, I need to generate NAD+
— Yeast will produce ethanol and NAD+ as byproduct)
— can produce lactate and make NAD+ from NADH

20
Q

Major regulatory enzyme in glycolysis

A

Phosphofructokinase

21
Q

What sets these three enzymes apart?

A

They are irreversible reactions!!

These are the rate limiting steps. You can’t go back. They are regulatory points. Committed.

22
Q

Where is glycolysis regulated?

A

Muscles
Liver

23
Q

What is the trigger from the muscles to speed up glycolysis?

A

AMP levels building up

24
Q

How do muscles know they need energy?

What will they do?

What is produced?

A

When ATP levels are low

Your muscles will use two ADPs to make ATP

ADP + ADP >< ATP + AMP

AMP will build up

AMP is the trigger to speed up glycolysis

25
Q

Glycolysis won’t run when ATP levels are…..

A

We don’t run glycolysis when ATP levels are high.

26
Q

Three main regulatory enzymes

A

Hexokinase
PFK
Pyruvate kinase

One direction reactions

27
Q

What do muscles need?
What do they do if they can’t get it?

A

ATP
When ATP is low, they can grab 2 ADPs and make ATP
AMP is byproduct

ADP + ADP >< ATP + AMP

When ADP levels go down, AMP goes up.
This is what muscles pay attention to, the ADP levels

28
Q

In terms of ATP, when do we switch glycolysis off?

A

When energy needs are met (high ATP) — turn OFF glycolysis

29
Q

When levels of …… are …. glycolysis is turned ON

A

When AMP is high — turn ON glycolysis because muscles need energy

30
Q

Describe the two sites on PFK
Active site
Allosteric site

What binds here?

A

PFK has an active site for the substrate Fructose 6-phosphate + ATP = Fructose 6-bisphosphate

It also has an allosteric site: has affinity (can bind) for ATP and AMP and it’ll impact the function of this protein.

How do you know which it’ll bind? It depends on if we need energy or not:

ATP is the inhibitor if we have enough ATP. It blocks the active site when it binds to the allosteric site.

AMP is the activator because we need ATP. AMP kicks out the ATP.

Remember ADP + ADP > ATP + AMP
This is non-competitive inhibition

31
Q

When ATP levels are low, what are AMP levels? Is PFK1 active or inactive?

A

ATP levels are low
AMP are high
PFK1 needs to be active

32
Q

When ATP levels are high, what are AMP levels? Is PFK1 active or inactive?

A

ATP levels are high
AMP levels are low
PFK1 is inactive

33
Q

What happens to hexokinase if there is excess G6P?
What does glucose do?
What happens to G6P?

A

Excess G6P shuts down hexokinase to stop bringing in the glucose.

Remember if glucose enters a cell and there is no hexokinase, it’ll head back out again.

G6P can be stored as glycogen

34
Q

What is feed forward stimulation?

A

F6BP will build up if pyruvate kinase isn’t activated

Pyruvate kinase is activated by fructose 6-bisphosphate
(Slide 12)

35
Q

Liver cares about what?

A

Liver cares about glucose.
It doesn’t care about energy (ATP) levels

Any glucose left over after used by brain/muscles will go to the liver.

Glucose needs to avoid the kidneys — cannot process here — too big!!

36
Q

What happens in the liver if glucose is high?

A

If glucose is high — activate glycolysis — to break it down!

Controlled by insulin — hormone signal saying “glucose levels high”

37
Q

What does the liver do when glucose is low?

A

Glucose is too low — stop glycolysis — don’t want to break any more down. Will send any remaining sugar to the brain.

Liver needs to synthesise:
1. Pull it from glycogen (glucagon) (storage)
2. Or from gluconeogensis (make it from scratch)

38
Q

Why doesn’t the liver have AMP? And the muscles do?

A

Muscles have AMP because when they desperately need ATP they’ll use two ADPs to make ATP and AMP

Liver doesn’t make ATP !

39
Q

What can the liver do if glucose is high, but PFK isn’t keeping up?

A

Glucose is high
PFK is high but not keeping up

F26BP will complete with ATP and open the active site up (like AMP in the muscles). This is when F6P starts to build up and PFK can’t keep up, so it makes F26BP. It’s a kinase — adding a phosphate.
Slide 17

To reverse this, liver doesn’t have ATP to compete it out. So just turn this enzyme F26BP off/get rid of it by dephosphorylate and send it back to F6P. Need a phosphotase to do this. (Slide 18)
One protein can do this! PFK-2 has 2 enzyme active sites.

40
Q

Describe what happens in the liver when glucose is high and PFK can’t keep up

A

Slide 21

41
Q

Describe what happens in the liver when glucose is low and need to shut down PFK

A
42
Q

Summarise glycolysis regulation during exercise

A
43
Q

Summarise glycolysis regulation during rest

A
44
Q

Summarise glycolysis regulation during rest

A
45
Q

Signal transduction

A

Look at the drawing of hormones and GPCR + audio

46
Q

Lecture in week 9 picked up from slide 5 “sources of glucose”

A

Reference slide