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Principles of Bioenergetics

Lehninger 3rd ed. Chapter 14

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Metabolism

•  A highly coordinated cellular activity aimed at achieving the following goals: – Obtain chemical energy. – Convert nutrient molecules into the cell’s

own characteristic molecules. – Degrade biomolecules.

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Carbon Flow

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Nitrogen Flow

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Catabolism & Anabolism

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Divergence & Convergence

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Synthesis versus Degradation

•  Most cells posses the enzymes to both synthesize and degrade a particular molecule. Is this not wasteful?

•  No, since the cell: – Regulates each process. – Segregates their location.

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Antoine Lavoisier

“…respiration is nothing but a slow combustion of carbon and hydrogen…” (A.L. Lavoisier 1743-1794)

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Bioenergetics

•  The quantitative study of cellular energy transductions and the chemical reactions underlying these transductions.

•  Obviously, biological energy transductions obey the laws of Thermodynamics.

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ΔG = ΔH −TΔS

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•  G: Gibbs free energy at constant temperature and pressure; Units are Joule per mole.

•  H: Enthalpy; Units are Joule per mole. •  Τ: Temperature; Units in Kelvins. •  S: Entropy; Units are Joule per mole

times temperature in Kelvins. €

ΔG = ΔH −TΔS

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ΔG: Free Energy at constant temperature and pressure (Joules per mole)

•  If ΔG < 0 then the reaction will be spontaneous. •  The value of ΔG is directly related to the equilibrium

constant

•  Actual free energy depends on the reactant and product concentrations: aA + bB cC + dD

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ΔG0 = −RT lnKeq

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ΔG = ΔG0 + RT ln [C]c[D]d

[A]a[B]b

12 Free energies are additive, thus a favorable reaction (ΔG1 < 0) can drive an unfavorable reaction (ΔG2 > 0), when ΔG1 + ΔG2 <0

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•  According to Boltzmann: S = k ln W where W is the number of states in the system.

•  Thus any reaction such as ��� aA + bB ⇌ cC + dD ���

in which a+b < c+d, can be said to be driven by entropy.

S: entropy

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C6H12O6 + 6O2 → 6CO2 + 6H2O

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Phosphoryl groups and ATP

•  ATP: Adenosine triphosphate, a ribo-nucleotide, is the energy currency of the cell.

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•  Relieves electrostatic repulsion between the negatively charges phosphates.

•  Inorganic phosphate can be stabilized by resonance hybrid.

•  ADP2- can ionize. •  The products are better solvated than the

reactants.

Why is the hydrolysis of ATP highly exergonic?

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ΔG' 0 = −30.5kJ /mol

Under standard conditions:

But in the cell the phosphorylation potential ΔGp is:

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ΔGp = ΔG' 0 + RT ln [ADP][Pi][ATP]

= −51.8kJ /mol

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ATP4− +H2O→ ADP3− + Pi2− +H+

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High Energy Phosphorylated Compounds

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Thioesters hydrolysis is also highly exergonic

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Making use of ATP

•  Since the ATP hydrolysis is very favorable (i.e. ΔG << 0) it can drive unfavorable reactions, but how?

•  It does so not by “harnessing” the energy of hydrolysis, but rather through the coupling of group transfer.

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Biological Oxidation-Reduction

•  The flow of electrons can do work. •  Electrons flow from a reducing agent to an

oxidizing agent due to their different electron affinities.

•  This difference in affinities is called the electromotive force (emf).

•  The reducing agent undergoes oxidation and the oxidized undergoes reduction.

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Redox reactions can be described as Half-reactions:

Fe2+ + Cu2+ ⇌ Fe3+ + Cu+

(1)  Fe2+ ⇌ Fe3+ + e- (2)  Cu2+ + e- ⇌ Cu+

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Redox reactions in bio-chemicals

2OH-+2Cu2+ Cu2O H2O+2e-+

R

C

O

H

R

C

O

O

H

R

C

O

H

R

C

O

O

H

+ 4OH- + 2Cu2+ + Cu2O 2H2O+

+ 2OH- + 2e- H2O+

29 Electronegativity series: O > N > S > C > H

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Dehydrogenation = oxidation

•  Carbon is less electronegative than all atoms it is bound to, except hydrogen.

•  Thus all atoms that bind to carbon oxidize it except hydrogen.

•  Thus removing a hydrogen and replacing that bond with any other atom (including carbon) is synonymous with oxidation.

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Electron transfer modes •  Directly as electrons:���

Fe2+ + Cu2+ ⇌ Fe3+ + Cu+ •  As hydrogen atoms:���

AH2 ⇌ A + 2e- + H+ •  As a hydride ion (H-):���

AH2 + B+ ⇌ A + BH + H+ •  Direct combination with oxygen:���

R-CH3 + 1/2O2 ⇌ R-CH2-OH

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Reduction potentials = e- affinity

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E = E 0 +RTnℑ

ln [electron acceptor][electron donor]

= E 0 +0.026V

nln [electron acceptor]

[electron donor]ΔG = −nℑΔE, or ΔG' 0 = −nℑΔE ' 0

ℑ = 96,480 J/V ⋅molR = 8.315 J/mol ⋅K

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Glucose oxidation is highly exergonic

•  The complete oxidation of glucose is our major source of energy.���

C6H12O6 + 6O2 → 6CO2 + 6H2O •  The process involves many steps each catalyzed

by a specific enzyme.���

ΔG’0 = -2,840 kJ/mol

35 NAD+, NADP+, FAD & FMN:���universal electron carriers

•  NAD+ (nicotinamide adenine dinucleotide) and NADP + (phosphorylated form of NAD+) are reversal redox cofactors in which.

•  In their capacity as reducing agents, the substrate undergoes a double dehydrogenation (oxidation) and NAD+ (or NADP+) accepts a hydride ion (H-), with a release of a H+ to the environment.

NAD+ + 2e- + 2H+ ⇌ NADH + H+���

CH3CH2OH + NAD+ ⇌ CH3CHO + NADH + H+

Ethanol

Acetaldehyde

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C

O

O

H

N

N

C

H

3

N

Nicotinic acid Nicotine

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FMN, FAD and flavoproteins •  Flavoproteins are enzymes that use FMN or FAD

cofactors in redox reactions. •  The cofactor is derived from riboflavin (vitamin

B2). •  FAD and FMN can accept either 1 or 2 hydrogens,

thereby accepting 1 or 2 electrons, and are therefore more versatile than NAD+ or NADP+.

•  The fully reduced forms are written as FADH2 and FMNH2

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N

N

N

H

C

H

3

C

H

3

N

O

O

C

H

2

C

H

O

H

C

H

O

H

C

H

O

H

C

H

2

O

H

Riboflavin (B2)

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