1. Introduction to Enzymes
(Chapter 12)
Department of Biochemistry and Molecular
Biology
LSUMC Shreveport, La

2. Enzymatic Catalysis Suited to
Biological systems
 Higher reactions rates
 Milder reaction conditions
 Greater reaction specificity
 Capacity for regulation

3. Enzyme-substrate interactions-a
prerequisite for catalysis
 Forces Important for
substrate recognition
 Active Site
Characteristics

4. Models for Enzyme Substrate Interactions
LOCK AND KEY INDUCED FIT

5. Carboxypeptidase A-Substrate Induced
Changes in Active Site Conformation

6. Enzyme Cofactors
N
N
N
H
2 O
O O
O
N
N
CH
H
2
H
H H
O
P
O
O
O
P
O
O
O
P
O
O
-
- - -
ATP

7. Enzyme Cofactors
+ -
+
N
O CH
H
2 O
H O O
H
H
O
P
O
-
N
N
N
H
2 O
O O
O
N
N
CH
H
2
H
H H
P
O
O
-
O
O
C-NH
2
H
+
N
O CH
H
2 O
H O O
H
H
O
P
O
-
N
N
N
H
2 O
O O
O
N
N
CH
H
2
H
H H
P
O
O
-
O
O
C-NH
2
H H
+ H + 2e
-
- H - 2e
..
+
NAD NADH

8. H
HS-CH -CH -N-C-CH -CH -N-C-C-C-CH-N
N
N
H
2 O
O O
O
N
N
CH
H
2
H
H H
O
P
O
-
O
P O
O
2 2
O
H
CoASH
O
-
2
O O
H
CH
3
CH
3
2
H
2
Enzyme Cofactors

9. Enzyme Classifications
Oxido-reductases
+ +
CH -CH -OH + NAD CH -CH=O + NADH + H
3 2 3
ALCOHOL DEHYDROGENASE
Transferases
++
O O
Mg
ATP + + ADP
HEXOKINASE
O
CH OH
2
OH
OH
HO
O
-
O
O
CH O
2
P -
OH
OH
H HO OH

10. Enzyme Classifications
Hydrolases
PROTEASE
O O
R-NH -CH-C-NH-CH-C-NH-R
R R
1 2
+ H O
2
R-NH-CH-C-OH
R
1
O
NH -CH-C-NH-R
2
R
2
O
+
Lyases
- O
ENOLASE
O
O P
O
-
-
CH -OH
O-C-H
C-O
O
O
O P
-
- C-O
O
2
-
CH
O-C + H O
2
2

11. Enzyme Classifications
Isomerases
O
C-O
O-C-H
-
O
CH -O
TRIOSE PHOSPHATE ISOMERASE
Ligases
O
- O P
O
-
CH -OH
2
C-O
-
2
O
P O
O
-
-
HO-C-H
O O
CH -C-OH + CoASH + ATP
ACETYL CoA SYNTHETASE
3
CH -C-S-CoA + AMP + PPi
3

12. Enzymatic Reactions of High Structural Specificity
H N-C-NH-(CH ) -CH-C-0-CH -CH H N-C-NH-(CH ) -CH-C-O
2
NH
2
2 3 2 3 2
O
NH
NH 2
C O
2 3
O
-
NH
C O
+
+
TRYPSIN
FAST
(1000x)
HCH-C-0-CH -CH
O
2 3
TRYPSIN
SLOW
HCH-C-0
O
-
NH
C O
NH
C O
Hydrolysis

13. Enzymatic Reactions of High Structural Specificity
HOH C O CH
OH HO
O
O
O
-
P O
2
2
-
O
-
O
O
O
O
CH OH
2
P
-
OH
OH
HO
O-O
O
O
CH O
2
P
-
OH
OH
Isomerization
HO
OH
PGM
FAST
-
O CH OH
OH HO
2
H C
2
O
O
O
- O P
PGM
SLOW

14. Enzymatic Reactions of Low Structural Specificity
(CH ) -CH
3 2 O (CH ) -CH
3 2
OH
ADH
+ +
H + NADH NAD
ADH
CH -CH O CH -CH -OH 3
+ +
H + NADH NAD
3 2
Oxidation-Reducton

15. Enzymatic Reactions with Stereochemical
CO H
C
2
CO H
C
+
H N
2
+
3
CH
3
H
NH
H C
3
H
D-ALANINE
3
L-ALANINE
CO H
C
2
CH
3
O + NH
+
4
Specificity
D-AMINO ACID OXIDASE

16. + +
CH -CH -OH + NAD CH -CH=O + NADH + H
3 2 3
ALCOHOL DEHYDROGENASE

18. Catalytic vs Binding Specificity
 As opposed to lock and key model, enzyme
recognizes and binds transition state, better than
substrate
 For enzymes recognizing a variety of structurally
similar substrates, the tighter binding substrates
often are catalyzed to product slower than weaker
binding substrates

19. Enzyme regulation by metabolic end products