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.....