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Metabolic Pathways > Regulation: Glycolysis > Flashcards

Regulation: Glycolysis Flashcards

1
Q

What are the enzymes which regulate glycolysis?

A 
Hexokinase (1)
PFK 1 (3)
Pyruvate kinase (10)
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2
Q

What happens when hexokinase attaches to glucose?

A

Large conformational change observed when it clamps down of glucose.
Pacemaker of glycolysis.

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3
Q

How many isoenzymes are there of hexokinase?

A

4 - in mammals products of different genes.

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4
Q

Which hexokinase isoenzymes are in all cells except for the liver?

A

HK(I) and HK(II) and III

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5
Q

Which hexokinase isoenzyme is exclusive to the liver?

A

HK (IV) = glucokinase

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6
Q

What does HK (I-III) have a higher of than HK (IV)?

A

HK (I-III) has a higher Km for glucose than HK IV and is half saturated at 0.1mM of glucose.

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7
Q

When do HKs work maximally?

A

When coming in from a blood range of 3-5mM ex: in muscle.

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8
Q

How are the HK(I-III) inhibited and by what?

A

Inhibited allosterically by G6P its product when G6P reaches high concentrations.

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9
Q

What does HK (IV) ensure that lower glucose won’t be metabolised maximally in liver but allowed to go out into the bloodstream to other tissues?

A

The Km is always greater than 10mM

Is not inhibited by high glucose G6P.

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10
Q

How is HK IV inhibited ?

A

By the binding of a regulatory protein - when blood glucose is low (<5mM) it binds to a regulatory protein which sequesters HK in nucleus.

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11
Q

What happens when glucose rises in the liver cell?

A

6mM glucose blocks regulatory binding & HK (IV) and it enters the cytosol.
Downstream regulators enhance this.
HK (II and IV) are also regulated transcriptionally increased/decreases amount of HK synthesised as it is needed depending on the energy depends.

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12
Q

What is the valve of glycolysis?

A

Phosphofructokinase- 1 (PFK-1)

Rate limiting step - regulated allosterically and by hormone induced signalling/covalently.

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13
Q

What are the on switches for PFK-1?

A

AMP, ADP
Fructose 2, 6 - bisphosphate (activator in liver)- conversely inhibits fructose 1, 6- bisphosphate= turns of gluconeogenesis.

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14
Q

What are the off switches of phosphofructokinase -1?

A

ATP

Citrate

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15
Q

Which organ is the most important in terms of glucose metabolism timing?

A

Liver

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16
Q

What determines the cellular concentration of fructose 2, 6 biphoshphate?

A

The rates of synthesis by the enzymes which make and break it.

17
Q

If glycolysis is stimulated what is inhibited?

A

Gluconeogenesis.

18
Q

In the liver what regulates PFK2 and FBPase reciprocally?

A

Glucagon released when glucose levels are low.

Insulin is released when glucose levels are high.

19
Q

What is achieved by glucagon in the liver?

A

It is released when the glucose is low, bind receptors on liver cells. Glucagon signalling reduces fructose 2, 6 bisphosphate by phosphorylation and inactivation its synthesising enzyme PFK-2.
Glycolysis stops

20
Q

How is pyruvate kinase regulated/inhibited?

A

Allosterically by high concentrations of high energy indicators.
- ATP, acetyl CoA
- long chain fatty acids.
-alanine
allosteric activation by F1, 6- bisphosphate.

21
Q

How is pyruvate kinase inhibited/activated?

A

Direct phosphorylation and inhibition via glucagon signal transduction in live to stop glycolysis in liver when glucose is low.

22
Q

What are the two isoforms of pyruvate kinase?

A

PKM1 and PKM2

23
Q

How are the isoforms of pyruvate kinase exhibited?

A

Through differing rates of reaction.

Under transcriptional regulation including in cancer.

24
Q

What other cells besides hepatocytes have receptors for glucagon?

A

Adipocytes - glucagon mobilises the breakdown of fats for energy as glucose is not being used.

25
Q

Where are the receptors mainly for adrenaline?

A

Skeletal and fat cells.

26
Q

Adrenaline is released when?

A

Low blood glucose and fight/flight

- in muscle increases glycogen breakdown but unlike liver glucose for energy in the muscle cells so increase glycolysis.

27
Q

Which organ turns on/off glycolysis and gluconeogenesis?

A

Liver

28
Q

When is insulin released?

A

When blood glucose is high

29
Q

Where are the insulin receptors?

A

Liver, fat, muscle and other cell.

30
Q

What does insulin do?

A

It increases glucose uptake into cells and through glucose transporter proteins.
- increase glycogen synthesis in liver and muscle.

31
Q

How does insulin increase glycogen synthesis?

A

Dephosphorylating glycogen phosphorylase -> no glycogen catabolism
Activating the glycogen synthase enzyme.

32
Q

What is the product of insulin increasing glycogen synthesis?

A

glycolytic enzyme activity and acetyl coA production in liver

33
Q

What can acetyl coA be used for other than glycolysis?

A

For fatty acid synthesis in the liver and transported to adipocytes where fatty acids converted to triacylglycerol.

Metabolic Pathways (13 decks)

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