1. 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

2. Energy in Cells Aims – 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

3. Gibbs Free Energy:  G =  H - T  S  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 + P  V (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

4. Thermodynamics parameters are measured on real molecules. Helix formation = hydrogen bonds + stacking Entropic penalty for loop formation. CG UA UA U C C U }  G = -2.1 kcal/mol }  G = -1.2 kcal/mol loop  G = + 4.5 kcal/mol GC }  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.

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

6. unfolded folded  G fold = -7.53 kJ/mol At equilibrium  G tot = 0. Therefore: [X fold ]/[X un ] = exp(+ (7.53 × 1000) /(8.314 × 310)) = exp(2.92) = 18.5 Temp T = 273 + 37 = 310K

7. Membranes Permeable to water and some small molecules. Not permeable to large molecules. Not permeable to ions (because of hydrophobic interior of membrane). [X out ] [X in ] For concentration ratio of 100,  G memb =8.314 × 310 × ln(100) = 12 kJ/mol Molecules will not spontaneously go up a concentration gradient.  G 0 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. For charged molecules need to add potential term. Faraday = charge per mole of electrons no. of charges on ion

8. 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.

9. Free energy of chemical reactions n A A + n B B  n C C + n D D similarly for B, C, and D where Free energy change of reaction under standard conditions of 1 M concentration of each species. At equilibrium  G = 0. Therefore Define the equilibrium constant as Therefore at equilibrium

10. example: ATP hydrolysis ATP 4- + H 2 O  ADP 3- + H + + HPO 4 2-  G 0 = -30.5 kJ/mol. Therefore, K = exp(30.5 x 1000/8.314 x 310) = 1.38 x 10 5 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.

11. 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  G reaction 0. However – nothing is 100% efficient. Always get dissipation of energy as heat.

12. A + B  C + D Activation energy and catalysts  G act G0rG0r forward reaction rate = k[A][B]exp (-(  G 0 r +  G act )/RT) backward reaction rate = k[C][D]exp(-  G act /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...

13. Catalyzing some reactions can drive a particular pathway. Results in specific products not equilibrium distribution of products.

14. 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 Fe 2+  Fe 3+ + 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+4+ 2-2- 2-2-2-2- ++ ++ ++ ++ 4-4-

15. Oxidation Reduction Hydrogen ElementalThiosulphate SulphiteSulphate sulphide sulphur H 2 S S 0 S 2 O 3 2- SO 3 2- SO 4 2- Ammonium NitrogenNitrite Nitrate gas NH 4 + N 2 NO 2 - NO 3 - Redox reactions – always one thing reduced and one thing oxidized. (Redox reactions drive chemosynthesis – see next section on chemoautotrophs) A red + B ox  A ox + B red (Redox reactions occur in electron transport chains. See next section on respiration and photosynthesis) symbolizes electron transfer.

16. 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.....