Cross References with Lunine Textbook Have done: Background on Biomolecules – see 4.1-4.3...

Cross References with Lunine Textbook

Have done:

Background on Biomolecules – see 4.1-4.3

Prebiotic chemistry and RNA World – see 9.4-9.5

Replicators v. Autocatalysis – see 9.1-9.3

Will do:

Thermodynamics – see 7.4-7.5

Metabolism, Respiration, Photosynthesis – see 4.6-4.7 (also Molecular Biology of the Cell, Alberts et al.)

Extremophiles – see Chap 10

Energy in CellsAims –

Thermodynamics of molecular interactions and chemical reactions.

How do cells get their energy?

Metabolism. Respiration. Photosynthesis.

How did these processes evolve?

How did the first organisms get their energy?

Cyanobacteria

Anabaenopsis

a bloom of cyanobacteria

Gibbs Free Energy: G = H - TS

H is enthalpy – equivalent to heat energy – can be stored in physical interactions between molecules and in chemical bonds.

S is entropy – measure of randomness or disorder – how many configurations are accessible to the molecules.

Technicality: H = E + PV (heat input at constant pressure)

Spontaneous reaction: G < 0

if G > 0, reaction requires energy input.

At equilibrium G = 0

Think about ice/water

But before we get to all that, we need to understand the dreaded topic of

Thermodynamics

Thermodynamics parameters are measured on real molecules.

Helix formation = hydrogen bonds + stacking

Entropic penalty for loop formation.

CG

U A

U A

U

C

C

U

} G = -2.1 kcal/mol

} G = -1.2 kcal/mol

loop G = + 4.5 kcal/mol

G C} G = -3.0 kcal/mol

Example of RNA folding

Total G = - 1.8 kcal/mol

1 kcal = 4.184 kJ (specific heat capacity of water)

G = - 7.53 kJ/mol

This loop is stable at this temperature.

Will melt at higher temp. Stability is sequence specific.

Chemical potential = change in G when a molecule is added to a solution

]ln[0 XRTXX

standard chem pot in 1M solution

gas constant

R = 8.314 J K-1 mol-1

absolute temperature

in K

concentration of molecule X in moles/litre (M)

The concentration term comes from treating a solution like an ideal gas

unfolded folded

Gfold = -7.53 kJ/mol

]ln[0unXun XRT

foldfoldXfold GXRT ]ln[0

foldun

foldunfoldtot G

X

XRTG

][

][ln

At equilibrium Gtot = 0. Therefore:

RT

G

X

X fold

un

fold

][

][ln

[Xfold]/[Xun] = exp(+ (7.53 × 1000) /(8.314 × 310)) = exp(2.92) = 18.5

Temp T = 273 + 37 = 310K

Membranes

Permeable to water and some small molecules. Not permeable to large molecules.

Not permeable to ions (because of hydrophobic interior of membrane).

[Xout]

[Xin]

]ln[0outXout XRT

]ln[0inXin XRT

][

][ln

out

inoutinmemb X

XRTG

For concentration ratio of 100, Gmemb =8.314 × 310 × ln(100) = 12 kJ/mol

Molecules will not spontaneously go up a concentration gradient.

G0 of hydrolysis of ATP = -30.5 kJ/mol. Hydrolysis of 1 mole of ATP is more than enough to drive transport of 1 mole of X against the concentration gradient.

VzFX

XRTG

out

inmemb

][

][ln

For charged molecules need to add potential term.

Faraday = charge per mole of electronsno. of charges

on ion

Simple diffusion is passive – down the concentration gradient

A passive channel is a catalyst – speeds up reaction but does not change equilibrium

Carrier mediated – one molecule goes downhill whilst the other goes up. Sum of two is downhill.

Active transport – use chemical energy to pump a molecule uphill.

Free energy of chemical reactions

nAA + nBB nCC + nDD ]ln[0 ARTAA similarly for B, C, and D

BA

DC

nn

nn

rBBAADDCCr BA

DCRTGnnnnG

][][

][][ln0

00000BBAADDCCr nnnnG where

Free energy change of reaction under standard conditions of 1 M concentration of each species.

BA

DC

nn

nn

r BA

DCRTG

][][

][][ln0 At equilibrium G = 0. Therefore

Define the equilibrium constant as RTGK r0exp

KBA

DCBA

DC

nn

nn

][][

][][Therefore at equilibrium

example: ATP hydrolysis

ATP4- + H2O ADP3- + H+ + HPO42-

G0 = -30.5 kJ/mol.

Therefore, K = exp(30.5 x 1000/8.314 x 310) = 1.38 x 105

This is large: there would be much more ADP than ATP at equilibrium.

The cell is not at standard 1 M conc of all molecules.

The free energy available from ATP hydrolysis depends on the concentrations – estimated between -25 and -40 kJ/mol.

The Cell is Not at Equilibrium

Cell is in a non-equilibrium steady state governed by balance of input and dissipation of energy and balance of input of food molecules and output of waste.

Energy input from metabolism can drive the reaction in reverse.Keeps ATP conc high.

See also fig 4.22 of Lunine

Oxidation of reduced carbon compounds releases energy (gas/oil/food)

Need to control this. An explosion in the gas tank does not make the car go far.

When Greaction < 0 for a reaction, this energy can in principle be used to form molecules for which Gformation > 0.

However – nothing is 100% efficient. Always get dissipation of energy as heat.

A + B C + D

RT

GK

BA

DC r0

exp]][[

]][[

Activation energy and catalysts

Gact

G0r

forward reaction rate

= k[A][B]exp (-(G0r + Gact)/RT)

backward reaction rate

= k[C][D]exp(-Gact/RT)

At equilibrium, forward and backward rates are equal. Therefore

The equilibrium constant does not depend on the activation energy.

A catalyst lowers the activation energy by binding to the transition state.

Speeds up both forward and backward reactions.

effect of catalyst

A+B

C+D

It can make you go uphill faster but it doesn’t keep you there...

Catalyzing some reactions can drive a particular pathway.

Results in specific products not equilibrium distribution of products.

H H H H | | \ \H-C-H H-C-OH C=O C=O O=C=O | | / / H H H HO

Oxidation – adding oxygen

Reduction – adding hydrogen

Methane Methanol Formaldehyde Formic acid Carbon dioxide

Oxidation – removing electrons

Reduction – adding electrons

Fe2+ Fe3+ + e-

C is more electronegative than H – in methane C is slightly negative

O is more electronegative than C – in carbon dioxide, C is slightly positive

Oxidation removes electrons from C.

0

+

+

4+2-2-2-

+

+

+

+4-

Oxidation

Reduction

Hydrogen Elemental Thiosulphate Sulphite Sulphate sulphide sulphur

H2S S0 S2O32- SO3

2- SO42-

Ammonium Nitrogen Nitrite Nitrate gas

NH4+ N2 NO2

- NO3-

Redox reactions – always one thing reduced and one thing oxidized.

(Redox reactions drive chemosynthesis – see next section on chemoautotrophs)

Ared + Box Aox + Bred

(Redox reactions occur in electron transport chains. See next section on respiration and photosynthesis)

symbolizes electron transfer.

Activated carrier molecules = energy currency

Adenosine triphosphate (ATP)

also transfers phosphate group

Acetyl coenzyme A (Acetyl CoA)

also transfers carbons

Nicotinamide adenine dinuclotide

NAD+

oxidizing agent

(electron acceptor)

NADH

reducing agent

(electron donor)All these molecules have nucleotide ‘handles’ with which they interact with enzymes. Probably used to interact with ribozymes. More evidence for the RNA world.

NAD+ + H+ + 2e- NADH

Half a reaction: the electron goes somewhere.....