5. Carbohydrates 3 - Regulation Of Metabolic Pathways

Question 1

What does allostery mean?

Answer 1

Allostery (allo = other, steric = site) - activator/inhibitor binds at
‘another’ site

Question 2

What are the two sites found in some proteins (usually enzymes)?

Answer 2

1. Catalytic site - where substrate binds and is converted to product
2. Regulatory/allosteric site - where specific regulatory molecules bind
   – Affects catalytic activity
   – can produce activation or inhibition

Question 3

How do regulatory molecules cause activation or inhibition?

Answer 3

The bind to the regulatory site and cause a change in the structure of the enzyme so that the active site changes shaped and the substrate is nor complementary so gets activated or non complementary so gets inhibited

Question 4

What is covalent modification?

Answer 4

(phosphorylation/dephosphorylation)
• Introduction of bulky negatively charged PO42- moiety
• Alters structure (protein conformation), alters activity

Question 5

Which steps are regulated and why?

Answer 5

• Irreversible steps are potential sites of
regulation 
• Reduced activity reduces the flux of
substrates through the pathway directly 
• Reducing levels of product

Question 6

Which steps are not regulated and why?

Answer 6

• Reversible steps are not regulated

* Even when inhibited, reactions still come to equilibrium so levels of product are unaffected

Question 7

What is product inhibition

Answer 7

A ——> B —-> C ——>D

• [C] increases, displaces B,C equilibrium
towards B
• reduces binding rate of B to active site C
• reduces rate of catalysis of B to C

• As pathway intermediates build so flux
through the pathway will slow

Question 8

What is feedback inhibition?

Answer 8

• allosteric inhibition by pathway
product on first enzyme in pathway
• Reduces entry of substrate and build up of intermediates in the pathway

Question 9

What happens when the commuting step is inhibited?

Answer 9

Inhibition of committing step allows substrate to be diverted into other pathways

Question 10

What are catabolic pathway inhibited by?

Answer 10

• Inhibited by high energy
signals
• ATP, NADH, FAD2H

Question 11

What are catabolic activated by?

Answer 11

• Activated by low energy
signals D
• ADP, AMP, NAD+, FAD

Question 12

Describe hormonal regulation

Answer 12

• Hormone receptor binding 
• Activates signalling pathway 
• Protein kinase (phosphorylation) or
protein phosphatase
(dephosphorylation) activated 
• phosphorylation/dephosphorylation of target enzyme 
• Alters protein conformation/activity
positively or negatively depending on the target enzyme

Question 13

What is feedforward?

Answer 13

Early pathway substrate provides positive allosteric signal to stimulate a later enzyme to activate the pathway

Question 14

What are two hormones involved in phosphoregulation?

Answer 14

Adrenaline and insulin

Question 15

Describe how adrenaline is involved in phosphoregulation

Answer 15

• Activates protein kinase A
• Phosphorylation activates phosphorylase kinase
• Phosphorylation of glycogen phosphorylase
- Stimulates glycogen breakdown

Question 16

Describe how insulin is involved in phosphoregulation?

Answer 16

• Stimulated signalling pathway activates protein phosphatase 1
• Dephosphorylates/activates pyruvate dehydrogenase
- stimulates glucose utilisation
• Dephosphorylates glycogen phosphorylase
- inhibits glycogen breakdown

Question 17

Is phosphorylation stimulatory or inhibitory?

Answer 17

Both depending on the target enzyme

Question 18

Which enzyme is the key regulatory enzyme in glycolysis?

Answer 18

Phosphofructokinase (PFK)

Question 19

What does phosphofructokinase catalyse?

Answer 19

Phosphorylation of fructose 6-P to fructose 1,6-P

Question 20

In allosteric regulation what stimulates Phosphofructokinase

Answer 20

• AMP

* Fructose 2,6 Bisphosphate

Question 21

In allosteric regulation, what inhibits Phosphofructokinase?

Answer 21

• ATP
• Phosphoenolpyruvate (PEP) - penultimate product of glycolysis
• Citrate (TCA cycle intermediate)
• H+ - acid

Question 22

In hormonal regulation what stimulates Phosphofructokinase?

Answer 22

Insulin - activates protein phosphate seems 1 which dephosphorylates phosphofructokinase

Question 23

In hormonal regulation, what inhibits Phosphofructokinase?

Answer 23

Glucagon - stimulates protein kinase A which phosphorylates phosphofructokinase-1

Question 24

Is Phosphofructokinase activated or inhibited by phosphorylation?

Answer 24

Inhibited

Question 25

Is Phosphofructokinase activated or inhibited by dephosphoryation?

Answer 25

Activated

Question 26

Apart from phosphofructokinase, where else in glycolysis is there regulation?

Answer 26

• In step 1, product inhibition of hexokinase by Glucose-6-Phosphate (G-6-P)
• metabolic regulation of step 6 ( where NADH is produced)
• hormonal regulation of pyruvate kinase

Question 27

In metabolic regulation of step 6, what causes the product inhibition?

Answer 27

• High NADH concentration = high energy levels, i.e. low [NAD+]
• Causes product inhibition of step 6
• Thereby, inhibition of glycolysis

Question 28

Which hormone stimulates pyruvate kinase?

Answer 28

Insulin - activates protein phosphate seems 1 which dephosphorylates pyruvate kinase used in step 10

Question 29

Which hormone inhibits pyruvate kinase?

Answer 29

Glucagon - activates protein kinase A which phosphorylates pyruvate kinase an inhibits it

Question 30

Describe inhibition of hexokinase?

Answer 30

• Inhibition at step 5, due to high [NADH] or low [NAD+] = high energy level signal
• Inhibition at step 3 PFK in response to high energy signals
• Prevents metabolism of F1,6-BP, backs up glycolytic intermediates, [G-6-P] increases
• G-6-P feeds back allosterically and inhibits hexokinase by product inhibition

Question 31

Where is the committing step in glycolysis?

Answer 31

Step 3 - where phosphofructokinase is used