enzyme Regulation

Question 1

Enzyme Regulation

Answer 1

Keeping it under CONTROL

Question 2

How are enzymes regulated by cells?

Answer 2

*controlling the RATE of enzyme synthesis or degradation
* putting the enzyme into a specific cell LOCATION or organelle
* association with a regulatory protein
* covalent post-translational modifications
* allosteric regulation

Question 3

Enzyme regulation by covalent modifications

Answer 3

Functional groups or small
molecules are covalently attached to specific amino acids in the enzyme

• this causes either an increase or decrease in the enzyme’s activity
• groups are usually added or removed by other enzymes!
• phosphorylation is the most common type of regulatory Covalent modification- SER/THREO/TYR
  kinases- on P
  Phosphotases - off P

Question 4

Glycogen phosphorylase and control by phosphorylation

Answer 4

• glycogen phosphorylase is an enzyme found in muscle and liver

Catalyzes the breakdown of
glycogen in those tissues to glucose-1-phosphate

Phosphorylation is a reversible covalent modification.

Question 5

covalent modifications

Answer 5

 Adenylylation- EP-Adenine
 Acetylation- Acetyl CoA
 Myristoylation- Myristoyl CoA
 Ubiquitination- Lysine! activated- NH-C=O
 Methylation

Question 6

ALLOSTERIC ENZYMES

Answer 6

regulated by molecules called allosteric effectors

allosteric enzymes are usually
composed of multiple subunits
OR domains

• and these enzymes often
  catalyze rate-limiting steps in
  pathways
• allosteric enzymes DO NOT
  follow Michaelis-Menten kinetics!

Question 7

Kinetics of allosteric enzymes

Answer 7

Since this is NOT M-M kinetics, the [S] at ½
Vmax is referred to K0.5
* SIGMOID KINETIC
BEHAVIOUR REFLECTS
COOPERATIVITY
BETWEEN MULTIPLE
SUBUNITS

Question 8

Allosteric enzymes undergo conformational
changes upon

Answer 8

effector binding/dissociation

example: Aspartate transcarbamoylase (ATCase) catalyses the rate
limiting step of pyrimidine biosynthesis

Question 9

Allosteric effectors

Answer 9

• binding of the effector can alter the enzyme’s
  ability to bind to its substrate, modify the
  maximal catalytic activity or BOTH…
• the binding of the effector is NOT at the active site

Effectors either
POSITIVE - INCREASE K0.5/Vmax
NEGATIVE- DECREASE K0.5/Vmax

Question 10

Types of allosteric effectors

Answer 10

1. Homotropic
   Heterotropic

Question 11

Homotropic

Answer 11

• substrate = allosteric effector
• usually these act as positive effectors
• binding of substrate on one site of the enzyme increases the
  catalytic properties of the enzyme at the active site: cooperactivity

Question 12

Heterotropic

Answer 12

effector is a molecule other than substrate
* act BOTH positively and negatively
* One example of heterotropic, allosteric regulation:
feedback inhibition

Question 13

Glutamine synthetase regulation

Answer 13

In all organisms, ammonia (NH4+) is
incorporated into glutamine by
glutamine synthetase

primary regulatory
point in nitrogen
metabolism!
glutamate + NH4+ + ATP  glutamine + ADP + Pi + H+

Each allosteric effector produces only a partial inhibition
 Effects of multiple inhibitors are more than additive
 Cummulative or synergistic feedback inhibition