The next four classes
Substrate binds at enzyme active site.
Enzymes are catalysts that speed up reactions without being consumed themselves
What determines how fast this reaction can go? (and why?)
Getting to the transition state, because that is the most unfavorable (most unlikely) state in the reaction.
Hydrolysis of peptide bond has $\Delta G < 0$, but it's slow
rate constant = $k = 1.5 \times 10^{-9}\ s^{-1}$
$k = 0.05\ years^{-1}$. That means 20 years to break a bond!
(resonance structure stabilizes substrate structure)
Peptide hydrolysis goes from $k = 1.5 \times 10^{-9}\ s^{-1}$ in water (pH 7) to $k = 120\ s^{-1}$ with enzyme
A 100-billion-fold speed up. Once every 20 years to 120 times per second!
How much does the enzyme lower the energy barrier for this reaction?
This is an important step for figuring out how the enzyme works
You are given a single, six-sided dice.
Rate of rolling sixes:
$k_{6} = k_{rolling} \times P_{6}$
If you roll a fair dice once per second, you get a rate of:
$k_{6} = 1\ s^{-1} \times \frac{1}{6} = 0.167\ s^{-1}$
Rate is determined by rolling rate and probability of 6
To speed up the rate, roll faster or weight the dice
For the reaction $E + S \rightleftarrows E \cdot S \rightleftarrows E + P$:
If the rate-limiting step is formation of $E \cdot S$, then we're interested in the left side
$k_{E\cdot S} = k_{try} \times P_{E+S\rightarrow E\cdot S}$
A small change in the transition state free energy can lead to large change in rate
(A change worth a few hydrogen bonds gives a 100-billion fold speed up)
Construct a "path" of low energy intermediates to overcome the energy barrier