1. Introduction to Enzymes
Biological Catalysts

2. Life Process = Chemical Reactions
Enzymes
A B C D E F
Enzyme 1
Enzyme 2
Enzyme 3
Enzyme 4
Enzyme 5

3. Chemical Reactions
Spontaneous and Fast
Spontaneous but Slow

4. Types of Reactions
Spontaneous Reactions: thermodynamically or energetically favorable
Kinetically Unfavorable Reactions
Requirement for Catalysts
Protein Catalysts: Enzymes
RNA Catalysts: Ribozymes
Perform the same function as chemical catalysts (ie increase reaction rate, are not used up in the rxn etc) but they do it better!

5. General Properties of Enzymes
Higher reaction rates (catalytic power)
Milder reaction conditions
Greater reaction specificity
Capacity for regulation

6. Higher Reaction Rates Carbonic Anhydrase
105 molecules CO2 per enzyme molecule per second
107 x uncatalyzed reaction

7. Catalytic Power of Some Enzymes
1 but still orders of magnitude higher than chemical catalysts
Table 11-1

8. Mild Reaction Condition
Physiological pH = ~7.3
Temperature = ~37°C
2. ch. Require high temp and pres.

9. Greater Reaction Specificity
3. Very specific products from very specific reactants. Rarely has side reactions
Table 11-1

10. Capacity for Regulation
Allosteric (Regulatory) Enzymes
Covalent Modification
Irreversible
Reversible
Non-covalent Modification
4. Substrate availability of course controls enzyme rate, but many other things can influence enzyme rate as well (allosteric regulators, covalent modification, and control of expression)

11. Enzyme Classes Oxidoreductases: oxidation-reduction reactions
Transferases: transfer of functional groups
Hydrolases: hydrolysis reactions (cleavage and introduction of water)
Lyases: group elimination to form double bond
Isomerases: isomerization (intramolecular rearrangements
Ligases (synthases): bond formation coupled with ATP hydrolysis

12. Enzyme Nomenclature (Usual usage: often use suffix –ase)
Common Name:
Useful but sometimes ambiguous
Examples: Urease/Arginase
Exceptions to the –ase suffix:
Trypsin/Chymotrypsin
Systematic Name:
Substrate(s) Type of reaction-ase

13. Enzyme Nomenclature (Common Name versus Systematic Name)
Hydratase = addition or removal of water
Aconitase
Aconitate Hydratase EC

14. Enzyme Nomenclature (Common Name versus Systematic Name)
Hydratase = addition or removal of water
Aconitase
Aconitate Hydratase EC

15. Enzyme Nomenclature (Common Name versus Systematic Name)
Lactate Dehydrogenase
L-Lactate:NAD Oxidoreductase

16. Enzyme Nomenclature (Common Name versus Systematic Name)
Lactate Dehydrogenase
L-Lactate:NAD Oxidoreductase

17. Enzyme Catalysis

18. Reaction Pathway (Coordinate)

19. Transition State Diagram

20. Stabilizing the transition state

21. Catalysts

22. Pathway of Enzyme Catalysis

23. Substrate Specificity
Active Site
Lock and Key Model
Induced Fit Model
Stereospecificity: 3-point attachment
Geometric Specificity: e.g. trypsin and chymotrypsin

24. Principle of Complementarity
Geometric (physical) complementarity
Electronic (chemical) complementarity

25. Enzyme-Substrate Complex
Binding Site
Shape of active site is geometric complementarity, +/- is electronic complementarity.

26. Models of Complementarity
Induced Fit
Lock and Key

27. Enzymes are Stereospecific
Geometric and electronic complentarity allows for stereospecificity.

28. Aconitase Reaction
Prochiral Substrate
Chiral Product
Page 325

29. Stereospecificity in Substrate Binding
Figure 11-2

30. Enzymes Vary in Geometric Specificity (Alcohol Dehydrogenase)
Ethanol ——> Acetaldehyde
Methanol ——> Formaldehyde
Isopropanol ——> Dimethylketone
RATE: Ethanol > Methanol > Isopropanol
Although this is rare most enzymes are fairly specific for their substrates.

31. Trypsin and Chymotrypsin

32. Trypsin
Long positively charged side chain

33. Chymotrypsin
Aromatic side chain

34. Some Enzymes Require Cofactors

35. Cofactors Simple Proteins (no cofactor) Protein plus Cofactor
Apoenzyme: protein only
Holoenzyme: protein plus cofactor
Apoenzyme + cofactor Holoenzyme
(inactive) (active)

36. Transiently Associated
Types of Cofactors
Organic Cofactor
Coenzyme: organic cofactor
Cocubstrate
Transiently associated (bound and released during catalytic cycle).
Prosthetic Group: tightly bound cofactor
Permanently associated, often covalently.
Transiently Associated
Permanently
Associated
Figure 11-3

37. Metal Ions
This is why trace elements are essential (like Se and copper) there are essential enzymes that require them for function.
Also why heavy metals are toxic, they are bind in place of the cofactor, but can’t perform catalysis.
Metal ions are stabiliy associated with enzymes (not bound and released during catalytic cycle)

38. Coenzymes: Cosubstrates [NAD(P)+ ——> NAD(P)H + H+]
Figure 11-4

39. NADP+

40. NADPH

41. Coenzymes: Cosubstrates (Alcohol Dehydrogenase)
Binds with the substrate; participates in catalysis and then is released
Page 327

42. Coenzymes: Prosthetic Groups (Cytochromes)

43. Coenzymes Must be Regenerated
Alcohol Dehydrogenase
Cytochromes
Cosubstrates by other enzymes
Prosthetic groups during catalytic cycle
Cosubstrate:
Different enzyme
Prosthetic group:
Same enzyme

44. Control of Enzyme Activity

45. Irreversible Covalent Modification
Zymogen Activation
Proteolysis
Lysosomes
Proteosomes (ubiquitin)

46. Zymogen Activation

47. Reversible Covalent Modification

48. Non-covalent Modification
Effectors or Ligands

49. Negative Effectors

50. Positive Effectors

51. Allosteric Proteins

52. General Properties of Enzymes
Biological Catalysts
Not used up in the reaction (Regenerated)
Higher reaction rates (catalytic power)
Within a biologically relevant time frame
Milder reaction conditions
Biologically appropriate conditions
Greater reaction specificity
Capacity for regulation
Control of substrate and product availability