Introduction to Enzymes 
(Chapter 12) 
Department of Biochemistry and Molecular 
Biology 
LSUMC Shreveport, La
Enzymatic Catalysis Suited to 
Biological systems 
 Higher reactions rates 
 Milder reaction conditions 
 Greater reaction specificity 
 Capacity for regulation
Enzyme-substrate interactions-a 
prerequisite for catalysis 
 Forces Important for 
substrate recognition 
 Active Site 
Characteristics
Models for Enzyme Substrate Interactions 
LOCK AND KEY INDUCED FIT
Carboxypeptidase A-Substrate Induced 
Changes in Active Site Conformation
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
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
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 
H 
CoASH 
O 
- 
2 
O O 
H 
CH 
3 
CH 
3 
2 
H 
2 
Enzyme Cofactors
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
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
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
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
Enzymatic Reactions of High Structural Specificity 
HOH C O CH 
OH HO 
O 
O 
O 
Isomerization 
- 
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 
HO 
OH 
PGM 
FAST 
- 
O CH OH 
OH HO 
2 
H C 
2 
O 
O 
O 
- O P 
PGM 
SLOW
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
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
+ + 
CH -CH -OH + NAD CH -CH=O + NADH + H 
3 2 3 
ALCOHOL DEHYDROGENASE
Ch12 enzymes can be taught
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
Enzyme regulation by metabolic end products

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Ch12 enzymes can be taught

  • 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. 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 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 Isomerization - 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 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