Enzymes

I. Introduction

• What are enzymes?
• What do they do?
• Brief historical review
• Pasteur
• Buchner, Sumner, Northrup
  
• Naming & Classification of Enzymes
  

-most enzymes have been named by adding "-ase" to the name of its substrate

-The EC System PROWL

II. Free energy of activation and the effects of catalysts

A. How fast will chemical reactions proceed?

• Thermodynamic reality
  
• Consider the following situation:
  

A A A A A A A A

A A A A A A

A A A A A

A A A A A

A+A => P

"metastable states"

What are they and why are they important?

What determines the rate of the conversion of "A" to "P"?

-Maxwell-Boltzman Distribution

-The relationship between kinetic energy of "A" and the progress of the reaction

-E_a or activation energy.

• Would an enzyme be able to speed up the rate of this reaction if the kinetic energy of "P" was higher than "A"?
  
• How can the reaction rate be increased?
  
• The effect of a catalyst on reaction rate:
  

B. The transition state

• The basic reaction associated with enzyme catalysis:
  

E + S <=> ES <=> E + P

• The active site
• The binding of the enzyme and substrate is not a "lock and key" association; induced fit animation
  
• The active site has a number of conformations
  
• What happens to the substrate in the active site?
  

C. Chemical Kinetics

Reaction order

-zero order

-first order

-second order

-third order

First order:

A reaction that proceeds at a rate exactly proportional to the concentration of one reactant.

example:

A  => P

A plot of [A] vs. time

A rate equation:

A = A₀e^-kt

where A = the concentration of A at time "t"

A₀= the concentration of A at time "0"

k = rate constant (units of reciprocal time)

A value for "k" can be easily calculated by the following relationship:

t_1/2 = 0.693/k

where t_1/2 = time required for half of the initial reactant to be consumed.

Second order:

The rate of the reaction is proportional to the product of the concentrations of two reactants.

A + B => P

Zero order:

Chemical reactions which are independent of the concentrations of any reactant are considered zero order.

D. Kinetics of Enzyme Catalyzed Reactions

• Enzymatically catalyzed reactions show saturation.
  
• A plot of reaction rate (v) vs. substrate concentration: identify first, mixed and zero order regions
  
• "turnover number"

-1913: L. Michaelis & M. Menton

• K_m