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CHMI 2227E

Biochemistry I
Enzymes:
- Regulation

CHMI 2227 - E.R. Gauthier, Ph.D. 1


Regulation of enzyme activity

CHMI 2227 - E.R. Gauthier, Ph.D. 2


Regulation of enzyme activity
1. Allostery

CHMI 2227 - E.R. Gauthier, Ph.D. 3


Regulation of enzyme activity
1. Allostery

ATCase

Carbomoyl Asp
phosphate

CHMI 2227 - E.R. Gauthier, Ph.D. 4


Regulation of enzyme activity
1. Allostery - ATCase

CHMI 2227 - E.R. Gauthier, Ph.D. 5


Regulation of enzyme activity
1. Allostery - ATCase

CTP
ATCase

CHMI 2227 - E.R. Gauthier, Ph.D. 6


Regulation of enzyme activity
2. Regulatory subunits

ATP

Adenylate
Cyclase

Phosphodiesterase
cAMP

cAMP
Caffeine

AMP

CHMI 2227 - E.R. Gauthier, Ph.D. 7


Regulation of enzyme activity
3. Regulation by covalent modification

CHMI 2227 - E.R. Gauthier, Ph.D. 8


Regulation of enzyme activity
3. Regulation by phosphorylation

CHMI 2227 - E.R. Gauthier, Ph.D. 9


Regulation of enzyme activity
3. Phosphorylation  Adrenaline
Adrenaline receptor Adenylate cyclase

Adrenaline
Outside the cell

    Inside the cell


G Protein 
 
ATP
Glycogen cAMP
(glucose stores) Protein Kinase A
Phosphorylase (inactive)
Glycogen kinase
Phosphorylase-PO4
ntracellular glucose PKA-cAMP
(active)
↑Energy
Phosphorylase
Kinase-PO4
Glycogen
Run Like Hell! Phosphorylase
CHMI 2227 - E.R. Gauthier, Ph.D. 10
Regulation of enzyme activity
4. Regulation of enzyme stability

CHMI 2227 - E.R. Gauthier, Ph.D. 11


Regulation of enzyme activity
4. Regulation of enzyme stability
Ub

E1
Ub

Enzyme
E1
E2
Ub

E2

E3
Ub
E3

Enzyme
Ub
Ub
Ub
Ub

CHMI 2227 - E.R. Gauthier, Ph.D. 12


Regulation of enzyme activity
4. Regulation of enzyme stability
Ub
Ub
Enzyme
Ub Ub
Ub
Ub
Ub
Ub

Proteasome

Degraded
enzyme

CHMI 2227 - E.R. Gauthier, Ph.D. 13


Regulation of enzyme activity
5. Limited proteolysis

CHMI 2227 - E.R. Gauthier, Ph.D. 14


Regulation of enzyme activity
5. Limited proteolysis

CHMI 2227 - E.R. Gauthier, Ph.D. 15


Regulation of enzyme activity
5. Limited proteolysis
Small intestine

Secreted by
pancreas

CHMI 2227 - E.R. Gauthier, Ph.D. 16


Regulation of enzyme activity
5. Limited proteolysis

CHMI 2227 - E.R. Gauthier, Ph.D. 17

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