9 - Regulation Of Metabolic Pathways

Question 1

What is allostery?

Answer 1

Where a regulator (activator or inhibitor) binds at ‘another’ site. Changes activity of enzyme

Question 2

What is covalent modification of an enzyme?

Answer 2

Enzyme gets de/phosphorylated, changing the conformity of the protein and therefore the activity

Question 3

What are the two ways of product inhibition in metabolic pathway?

Answer 3

1. Increase in conc of an intermediate in a reversible reaction leads to a shift in equilibrium. Binding rate of previous intermediate decreases so increase in pathway intermediates

2. Feedback inhibition - allosteric binding of end product to first enzyme in pathway. Reduces entry of substrate and therefore stops build up of intermediates

Question 4

What is the commiting step in a pathway?

Answer 4

Irreversible enzymatic reaction that once occurs, the molecules are comitted and will end up in the end product of the pathway

Question 5

What is the committed step of glycolysis?

Answer 5

Point where phosphofructokinase-1 phosphorylates fructose-6-p

Question 6

What reactions of glycolysis are regulated and why?

Answer 6

1, 3 and 10. They are irreversible. Reversible cannot be regulated as equilibrium will still be reached

Question 7

How can regulating the committing step affect a pathway?

Answer 7

Inhibiting the commiting step diverts substrate to other pathways. e.g product of pathway could allosterically inhibit enzyme for substrate

Question 8

How are catabolic pathway enzymes regulated?

Answer 8

• High energy signals : ATP, NADH, FADH₂ inhibit
• Low energy signals: AMP, ADP, NAD activate

Question 9

How can hormonal regulation affect metabolic pathways?

Answer 9

• Hormone binds to receptor
• This activates signalling pathway and therefore activates protein kinase or protein phosphotase
• These enzymes de/phosphorylate target enzymes involved in glycolysis and change their conformity so either activate or deactivate them

Question 10

What type of regulation is feed forward an example of?

Answer 10

• Allosteric
• Substrate provides positive allosteric signal to enzymes further down the pathway

Question 11

Give two examples of phosphoregulation with hormones.

Answer 11

Adrenaline

Activates protein kinase A.

Phosphorylation activates phosphorylase kinase and glycogen phosphorylase. Stimulate glycogen breakdown

Insulin

Activate protein phosphotase 1.

• Dephosphorylates pyruvate dehydrogenase, activating it and stimulating glucose utilisation.
• Dephosphorylates glycogen phosphorylase which inhibits it, inhibiting glycogen breakdown

Question 12

What is the key regulator of glycolysis?

Answer 12

Phosphofructokinase-1

(first commiting step)

Question 13

What does phosphofructokinase do?

Answer 13

Catalyse phosphorylation of fructose-6-p to fructose-1,6-p

Question 14

How is glycolysis metabolicaly inhibited?

Answer 14

High energy levels of NADH from step 5 causes inhibition of step 6 (phosphorylation)

Question 15

How is glycolysis allostericaly regulated?

Answer 15

Phosphofructokinase 1

Activated: AMP, F2,6-BP (high fructose levels)

Inhibited: ATP, PEP (last product of glycolysis), Citrate (Krebs), H+ (metabolism forms acid)

Hexokinase

Inhibited: G-6-P which builds up due to stop of step 4 and 6

Question 16

How is glycolysis regulated by hormones? (Phosphoregulation)

Answer 16

PFK1

Insulin –>Protein Phosphatase–> Dephosphorylate PFK–> +

Glucagon –> Protein Kinase A –> Phosphorylate PFK –> -

Pyruvate Kinase** **(Final enzyme)

Same as above

Question 17

Explain all of the ways glycolysis is regulated.

Answer 17

Question 18

How is step 1 of glycolysis regulated?

Answer 18

Hexokinase has product inhibition by G-6-P