Chemical kinetics:
Before examining enzyme catalysis it will be useful to review reaction rates of chemical reactions:
k
A ---> B, where k is the rate constant
This reaction is 1st order and has a velocity (d[B]/dt) of k[A]; if displayed in graphical form, this reaction gives the curve of a declining exponential function.
The integrated form of this equation is ln([A]/[A]o) = -kt
The rate of reaction increases linearly with increasing initial concentrations of A.
k
A + B ---> C (or the simpler case of 2 A ---> C)
This reaction is 2nd order and has a
velocity (d[C]/dt) of k[A][B] (or k[A]2 for the simpler case)
The integrated form of this equation is 1/[A] = 1/[A]o + 2kt.
It will be of interest to compare these kinetic expressions with those obtained later for enzyme catalysis.
Transition State and Reaction Rate:
G± = free energy of the
transition state (energy of activation)
The concentration of molecules with sufficient energy to be at the transition state (A*) is given by:
[A]* = [A]o e -G±/RT
Since only those molecules of A that achieve the energy of the transition state can be converted to product, the rate of reaction (k) is proportionate to the concentration of A*.
k = Qe -G±/RT;
where Q is
proportionality constant
or more simply:
k = Q'e -G±/RT
The pre-exponential term Q' now includes the entropy term TS/RT, which is constant as function of
temperature.
Roles of enzymes:
a. it speeds up chemical reactions by lowering the free energy of the transition state.
b. it insures the path of a sequence of reactions and is what creates biochemical pathways.
c. its catalytic activity can be regulated
Models for Enzyme Catalysis:
Enzymes facilitate chemical reactions by:
a. stabilizing a strained intermediate state (often the transition state configuration). The binding of this intermediate favors its accumulation and effectively lowers the amount of energy needed to attain it.
b. by binding substrate molecules, it helps orient two molecules (an entropy effect) so that their interaction favors the chemical reaction.
Lock and key - Induced fit
Emil Fischer (as early as 1894) proposed the lock and key model of enzyme catalysis (there is no strain in this model), which explains enzyme specificity but not catalysis.
Daniel Koshland ( in 1958) proposed the induced fit model of enzyme catalysis. In this model both the substrate and enzyme are distorted upon substrate binding.
A number of enzyme-catalyzed reaction mechanisms has been described in detail, please review the nature of the interactions between amino acids in the enzyme and the substrate, transition state, and products.
