Bioenergetics
• The study of energy transformations in living organisms
Review from Chemistry
• Thermodynamics
– 1st Law: Conservation of Energy (E)
• Neither created nor destroyed, but can be transformed into different states
– 2nd Law: Events proceed from higher to lower E states
• Entropy (disorder) always increases
– Universe = system + surroundings
(E content of system) H = (useful free E) G + (E lost to disorder) TS
• Gibbs Free Energy: G = H - TS
– If G = negative, then rxn is exergonic, spontaneous
– If G = positive, then rxn is endergonic, not spontaneous
– Standard conditions (ΔG°’)
• 25oC, 1M each component, pH 7, H2O at 55.6M
Review from Chemistry
A + B <--> C + D
• Rate of reaction is directly proportional to concentration of reactants
• At equilibrium, forward reaction = backward reaction
k1[A][B] = k2[C][D]
• Rearrange:
k1/k2 = ([C][D])/([A][B]) = Keq
• Relationship between ΔG°’ and K’eq is:
G°’ = -2.303 * R * T * log K’eq
If K’eq >1, G°’ is negative, rxn will go forward
If K’eq <1, G°’ is positive, rxn will go backward
Coupling endergonic and exergonic rxns
• The Problem: Many biologically important reactions are endergonic
Glutamic acid + NH3 --> H2O + Glutamine
H
+ NH3  H2O +
G°’=+3.4 kcal/mol
Coupling endergonic and exergonic rxns
• ATP hydrolysis is a highly exergonic reaction
• Frequently coupled to otherwise endergonic reactions
Coupling endergonic and exergonic rxns
• Partial reactions:
Glutamic acid + NH3 --> H2O + Glutamine G°’=+3.4 kcal/mol
ATP --> ADP + Pi
G°’=-7.3 kcal/mol
---------------------------------------------------------------------------------------Glu + ATP + NH3 --> Gln + ADP + Pi
G°’=-3.9 kcal/mol
+ ATP 

+ NH3
Glutamyl phosphate
is the common
intermediate
+ ADP + Pi
Equilibrium vs steady state
• Cells are open systems, not closed systems
– O2 enters, CO2 leaves
– Allows maintenance of reactions at conditions far from equilibrium
O2
Biological Catalysts
Biological Catalysts
1) Req’d in small amounts
2) Not altered/consumed in rxn
3) No effect on thermodynamics of rxn
a) Do not supply E
b) Do not determine [product]/[reactant] ratio (Keq)
c) Do accelerate rate of reaction (kinetics)
4) Highly specific for substrate/reactant
5) Very few side reactions (i.e. very “clean”)
6) Subject to regulation
No relationship between G and rate of a reaction (kinetics)
Why might a favorable rxn NOT occur rapidly?
Overcoming the activation energy barrier (EA)
• Bunsen burner: CH4 + 2O2 --> CO2 + 2H2O
– The spark adds enough E to exceed EA (not a catalyst)
• Metabolism ‘burning’ glucose
– Enzyme lowers EA so that ambient fluctuations in E are sufficient
Overcoming the activation energy barrier (EA)
Catalyst shifts
the dotted line
to the left
How enzymes lower EA
• The curve peak is the transition state (TS)
• Enzymes bind more tightly to TS than to either reactants or products
How enzymes lower EA
• Mechanism: form an Enzyme-Substrate (ES) complex at active site
– Orient substrates properly
for reaction to occur
• Increase local concentration
• Decrease potential for
unwanted side reactions
How enzymes lower EA
• Mechanism: form an Enzyme-Substrate (ES) complex at active site
– Enhance substrate reactivity
• Enhance polarity of bonds via interaction with amino acid functional groups
• Possibly form covalent bonded intermediates with amino acid side chains
Covalent intermediates
Covalent intermediates
How enzymes lower EA
• Mechanism: form an Enzyme-Substrate (ES) complex at active site
– Induce bond strain
• Alter bonding angles within substrate upon binding
• Alter positions of atoms in enzyme too: Induced fit
Induced fit
Induced fit
Enzyme kinetics: The Michaelis-Menten Equation
S <--> P
At low [S], velocity (rate) is slow, idle time on the enzyme
At high [S], velocity (rate) is maximum (Vmax), enzyme is saturated
V = Vmax [S]/([S] + Km)
Km = [S] at Vmax/2
A low Km indicates high enzyme affinity for S
(0.1mM is typical)
Irreversible Enzyme Inhibitors
• Form a covalent bond to an amino acid
side chain of the enzyme active site
• Example: penicillin
penicillin
– Inhibits Transpeptidase enzyme required for
bacterial cell wall synthesis
Reversible Enzyme inhibitors: competitive
• Bind at active site
• Steric block to substrate binding
– Km increased
– Vmax not affected (increase
[S] can overcome)
• Example: ritonavir
– Inhibits HIV protease ability to
process virus proteins to mature
forms
Reversible Enzyme inhibitors: noncompetitive
• Do not bind at active site
• Example: anandamide
(endogenous cannabinoid)
• Bind a distinct site and alter enzyme
– Inhibits 5-HT3 serotonin
structure reducing catalysis
receptors that normally
– Km not affected
increase anxiety
– Vmax decreased, (increase [S]
cannot overcome)
Competitive
Noncompetitive