bioenergetics the study of energy transformations in living organisms
TRANSCRIPT
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Bioenergetics• The study of energy transformations in living organisms
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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) TS
• Gibbs Free Energy: G = H - TS– 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
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Review from ChemistryA + 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 forwardIf K’eq <1, G°’ is positive, rxn will go backward
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Glutamic acid + NH3 --> H2O + Glutamine G°’=+3.4 kcal/mol
Coupling endergonic and exergonic rxns
+ NH3 H2O +
• The Problem: Many biologically important reactions are endergonic
H
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• ATP hydrolysis is a highly exergonic reaction• Frequently coupled to otherwise endergonic reactions
Coupling endergonic and exergonic rxns
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Glutamic acid + NH3 --> H2O + Glutamine G°’=+3.4 kcal/mol
ATP --> ADP + Pi G°’=-7.3 kcal/mol----------------------------------------------------------------------------------------
Coupling endergonic and exergonic rxns
+ ATP + ADP + Pi
+ NH3
Glu + ATP + NH3 --> Gln + ADP + Pi
Glutamyl phosphate is the common intermediate
G°’=-3.9 kcal/mol
• Partial reactions:
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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
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Biological Catalysts
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1) Req’d in small amounts2) Not altered/consumed in rxn3) No effect on thermodynamics of rxn
a) Do not supply Eb) Do not determine [product]/[reactant]
ratio (Keq)c) Do accelerate rate of reaction (kinetics)
4) Highly specific for substrate/reactant5) Very few side reactions (i.e. very “clean”)6) Subject to regulation
No relationship between G and rate of a reaction (kinetics)
Biological Catalysts
Why might a favorable rxn NOT occur rapidly?
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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
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Overcoming the activation energy barrier (EA)
Catalyst shifts the dotted lineto the left
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How enzymes lower EA• The curve peak is the transition state (TS)• Enzymes bind more tightly to TS than to either reactants or products
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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
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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
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Covalent intermediates
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Covalent intermediates
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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
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Induced fit
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Induced fit
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S <--> PAt low [S], velocity (rate) is slow, idle time on the enzymeAt 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)
Enzyme kinetics: The Michaelis-Menten Equation
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Irreversible Enzyme Inhibitors• Form a covalent bond to an amino acid
side chain of the enzyme active site• Example: penicillin
– Inhibits Transpeptidase enzyme required for bacterial cell wall synthesispenicillin
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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
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Reversible Enzyme inhibitors: noncompetitive• Do not bind at active site• Bind a distinct site and alter enzyme
structure reducing catalysis– Km not affected– Vmax decreased, (increase [S]
cannot overcome)
NoncompetitiveCompetitive
• Example: anandamide (endogenous cannabinoid)– Inhibits 5-HT3 serotonin receptors that normally
increase anxiety
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