Regulation of Metabolic Pathways

Question 1

What is allostery?

Answer 1

When an activator/inhibitor binds at another site to the active site

Question 2

What are the two sites that enzymes possess?

Answer 2

Catalytic Site - Substrate binds to become product (active site)

Regulatory Site - Regulatory specific molecules bind to this site, activating or inhibiting catalytic activity

Question 3

What is covalent modification?

Answer 3

Bulky -ve charged PO4 groups attach to enzyme and alters structure, altering activity

Question 4

What are the two types of reaction steps and which do we regulate and why?

Answer 4

Reversible and Irreversible reactions

We regulate irreversible steps bc. we can reduce product levels

We cannot regulate reversible steps bc. the reaction will reach equilibrium so product levels are unaffected.

Question 5

Describe feedback inhibition

Answer 5

Substrate A builds up bc its reaction is inhibited by a later product, eg. E

Is an Allosteric inhibition

If this occurs on the committing step, then the substrate builds up and can lead onto other pathways

Question 6

What is the best inhibiting enzyme in glycolysis?

Answer 6

Phosphofructokinase

Question 7

Regulation can be inhibitory or stimulatory. In catabolic pathways, which molecules inhibit/stimulate?

Answer 7

Inhibited by high energy molecules:
ATP, NADH, FAD2H

Stimulated by low energy molecules:
ADP, AMP, NAD+, FAD

Question 8

Describe hormonal regulation. Give an example.

Answer 8

Hormones bind to receptors and hence inhibit or stimulate enzyme activity (GPCRs)

Protein kinase or phosphatase phosphorylate or dephosphorylate target enzyme, altering its conformation and hence stimulating/inhibiting the enzyme.

Question 9

Describe feed forward process

Answer 9

Idea that a substrate from early in a process can stimulate enzymes later in the pathway

Question 10

Provide examples of phosphoregulation

Answer 10

1) Adrenaline activates Protein Kinase A
- Phosphorylates phosphorylase kinase
- Phosphorylates glycogen phosphorylase
- Stimulates glycogen breakdown

Question 11

How is step 3 of glycolysis regulated?

Answer 11

F6P becomes F16BP by phosphofructokinase

Allosteric regulation:
Inhibited by ATP
Stimulated by AMP

Hormonal regulation:
Stimulated by insulin
Inhibited by glucagon