Lecture 24- enzyme regulation

Question 1

Why are enzymes regulated?

Answer 1

To increase or decrease activity
Maintain metabolic effectiveness and avoids waste

Question 2

The slowest (rate limiting) step of a metabolic pathway is the most…..

Answer 2

efficient control point of the pathway

Question 3

How are rate limiting enzymes controlled?

Answer 3

By mechanisms that affect the catalytic site

Question 4

Regulatory mechanisms of enzymes:

Answer 4

Allosteric activation/inhibition
Phosphorylation (or other covalent modification)
Protein-protein interactions
Proteolytic cleavage

Question 5

Allosteric regulation

Answer 5

Activity modulation via reversible, non-covalent binding of small molecules
Bind at allosteric site

Question 6

Allosteric enzymes are ofter composed of ….

Answer 6

Multiple subunits

Question 7

Allosteric effector binding…

Answer 7

changes catalytic site conformation
(affects substrate binding)

Question 8

Advantages of allosteric regulation

Answer 8

Effectors as the bind to sites other than catalytic site
Can be activators (not just inhibitors)
Effectors don’t need to resemble substrate or product
Regulation is rapid

Question 9

if enzyme activity increases when the effete binds then…

Answer 9

it is an allosteric activator/positive effector

Question 10

Allosteric regulation affects …. and …

Answer 10

Enzyme affinity for substrate and/or maximal catalytic activity

Question 11

Homotropic effectors

Answer 11

The substrate serves as an allosteric effector

Question 12

Heterotrophic effector

Answer 12

The effector is different from the substrate
(eg. citrate: -ve effector for phosphofuctokinas- 1, important enzyme for glycolosis)

Question 13

Co-operativity

Answer 13

A homographic effector functions as a positive effector

Question 14

Positive co-operativity

Answer 14

When a substrate binds one subunit it can enhance the catalytic properties of the other subunits

Question 15

Negative co-operativity

Answer 15

Some substrates bind a subunit and it can reduce the catalytic properties of other subunits

Question 16

The concerted model

Answer 16

1st substate molecule has difficulty binding as all subunits in T state
All change to R state
All subunits exist in the same conformation

Question 17

The sequential model

Answer 17

Enzyme/protein molecule affinity is relative and changes as substrates bind
When substrate binds, molecules goes from T-state to R-state

Question 18

Covalent modification- enzyme regulation

Answer 18

Lead to conformational changes
eg.phosphorylation- addition of phosphate groups- mediated by ‘protein kinases’
Phosphate groups are removed by protein phosphates via hydrolysis

Question 19

Protein kinases

Answer 19

Some protein kinases only regulate one protein, others simultaneously regulate several rate-limiting factors

Question 20

Adrenaline …. the intracellular concentration of 3’,5’-cyclic AMP (cAMP)

Answer 20

increases

Question 21

Covalent modification examples

Answer 21

Addition/ removal of acetyl , ADP-Ribose to lipids

Question 22

Protein-protein interactions

Answer 22

Direct interactions between proteins can lead to conformation changes in the active site
eg. calcium-calm odium family of modulator proteins-modulates the activity of glycogen phosphorylase kinase
eg. G-proteins- contain an internal clock that slowly hydrolyses GTP

Question 23

Proteolytic cleavage

Answer 23

Enzymes can be irreversibly activated or inactivated by proteolytic enzymes
Degradation of enzymes by intracellular proteases on lysosomes or proteasomes determines enzymatic activity over a longer period

Question 24

Enzyme synthesis

Answer 24

Control of enzymatic activity can be made here
Induction/repression leads to an alteration in total population of active sites
This type of regulation often only needed at one point of development or under selected physiologic conditions