Life Sciences 1a
Practice Problems 7
1.
a) How many intermediates are there in the reaction?
b) How many transition states are there?
c) What is the fastest step in the reaction?
d) Which is more stable, A or D?
2. Which of the following are nucleophiles and which are electrophiles?
a)
b)
c)
d)
+
H
HO
H20
NH3
3. The first step in breaking down glucose is the conversion of glucose to glucose-6phosphate in the following reaction:
Pi + glucose
glucose-6-P + H2O
The ΔG° of this reaction is 13.8 kJ/mol.
a) Is this reaction favorable?
ATP can be hydrolyzed to form ADP and Pi in the following reaction:
ATP + H2O
ADP + Pi
The ΔG° of this reaction is -30.5 kJ/mol.
b) Is this reaction favorable?
c) If these two reactions are coupled, what is the overall ΔG° for both reactions?
d) If these two reactions are coupled, then overall are they favorable?
e) What is the reaction equation for the overall coupled reaction?
f) Explain why ATP is so important for living systems (in terms of ΔG).
4. Explain why the rate of a chemical reaction is dependent on concentration of
reactants in the reaction solution. How can an enzyme affect the ‘concentration’
of substrates and thereby alter the rate?
Free Energy
5. A chemist mixes equal numbers of molecules A, B, and C in a flask. Molecule B
can react with molecule A to make AB, or it can react with molecule C to make
BC. The reaction energy diagram for both reactions is below. This reaction
energy diagram assumes standard conditions.
Course of the Reaction
(Reaction Coordinate)
a) After a small amount of reaction time (when only a tiny amount of products
have been generated) does the chemist have more AB or BC? Briefly Explain.
b) After one hour of reaction time the chemist would like to have more of the
other product. Give two ways the chemist could accomplish this.
c) After equilibrium has been reached does the chemist have more AB or BC?
Briefly explain.
6. In lecture you saw how proteins can be broken down by hydrolysis, and how
acid and base catalysis can help this process occur. RNA is also broken down in
the presence of a base. The mechanism for the cleavage of RNA is drawn
below.
Base
O
O
P
O
O
H
H
OH
O
O
P
O
O
Base
O
H
-O
O
H
O
O
O-
P
O
H
O H
O
OO
O
Base
O
-OH
-OH
O H
Base
O
HO
Base
O
Base
HOO
OH
O
OH
H
a) While this reaction can proceed somewhat efficiently in the presence of a
base, an enzyme called RNase A uses acid-base catalysis to make this
reaction proceed even faster in a way that is similar to that used by HIV
protease. The active site of this enzyme has catalytic His residues instead of
the Asp residues found in HIV protease. One of these His residues is
unprotonated (a base) while the other is protonated (an acid). Explain how
these His residues can catalyze this reaction. Propose a transition state for
the reaction.
Base
O
O
N+
H
O-
P
O
N
O H
N
H
O
O
N
H
O
Base
OH
b) Draw the reaction energy diagram for this reaction with and without the
participation of the enzyme RNase A.
c) Do you think that RNase A would also be able to accelerate the hydrolysis of
DNA? Explain your answer.
1.
a)
b)
c)
d)
2, B and C
3
C
D
D
2. Which of the following are nucleophiles and which are electrophiles?
+
a) H
electrophile-likes electrons, can accept electrons
b) HO nucleophile-likes nuclei, has electrons to share
c) H20 nucleophile
d) NH3 nucleophile
3. Breaking down glucose
a) Not in the forward direction, ΔG°>0
b) Yes, it is in the forward direction, ΔG°<0
c) ΔG°= -16.7 kJ/mol
d) Yes, ΔG°<0
e) glucose +ATP
glucose-6-P + ADP
f) ATP hydrolysis is a highly favorable process (negative ΔG) and can
be used to drive other, non-favorable processes. The hydrolysis of
ATP to ADP releases a very large amount of energy. If this reaction
is coupled to a reaction that requires energy (positive ΔG) the
overall process will still release energy and can now occur.
4. For the reagents to react they have to be close enough to actually be
able to interact. The higher the concentration of reactants the more
likely it is for the two (or more) reacting partners to be close to each
other. An enzyme creates an artificially high local concentration of
substrates by bringing the reactants much closer together than they
would be if free in solution.
5. a) At first the product ratio is determined by the difference in the
activation energies of the reactions. Since the activation energy for
A+B+C→AB+C is lower than the activation energy for A+B+C→A+BC,
more AB will be formed initailly.
b)
Add heat (energy)
Add more B and C
Add a catalyst specific for the A+B+C→A+BC reaction
c) When the reaction is at equilibrium the ratio of products from the two
reactions is determined by the free energies of the products. Since the
free energy of A+BC is lower that the free energy of AB+C, more BC will
be formed.
6. a)
Base
O
O
N+
H
O
N
O H
O-
P
Base
O
O
O
N
H
O
O
O
N
H
P
H
Base
O
O
N
H
O
N
N
H
O
N
OH
H
OBase
OH
The unprotonated histidine acts as a catalytic base to deprotonate the 2’-OH
group, making it a stronger nucleophile. The protonated histidine acts as an
acid catalyst by protonating the oxygen attached to the 5’ carbon, this allows
the resulting –OH group to break away. [Note: this is only describing the
reaction up to the above intermediate].
b)
E + TS‡
E-TS‡
Uncatalyzed
reaction
E+S
E-S
Enzyme-catalyzed
reaction
E+P
E-P
The same picture as the figure from the lecture. [Note: the above
mechanism is really showing only half of the reaction]
c) No, DNA does not have a 2’-OH group, therefore its hydrolysis cannot be
catalysed by RNase A.