1. Bioorganic Chemistry and Biochemistry CHM3218 Summer C 2008 Dr. Lyons office hours lyons@chem.ufl.edu 846-3392 T,W 3-4 PM, R 9-10 AM Class website http://www.chem.ufl.edu/~lyons/

2. Test Dates May 27 June 17 July 11 July 25 August 8

3. Biochemistry is more than organic chemistry Medically important Toxic Questionably essential Cr 24

4. Bulk Hydrogen Carbon Nitrogen Oxygen Sodium Magnesium Phosphorous Sulfur Chlorine Potassium Calcium Manganese Iron Cobalt Nickel Copper Zinc Molybdenum Selenium Iodine Essential Trace

5. Other Elements Boron Silicon Vanadium

6. Environment is the key to understanding biological systems Iron as a case study

7. Geochemical considerations are critical for life

12. Effect of O 2 concentration on other elements

14. Iron as a Case Study Fe(H 2 O) 6 3+ ---> Fe(OH) 3 + 3H + + 3H 2 O K sp = [Fe 3+ ][OH - ] 3 ≈ 10 -38 M [Fe 3+ ] = 10 -38 /[OH - ] 3 At pH 7.0, [Fe 3+ ] = 10 -38 /(10 -7 ) 3 = 10 -17 M Fe(H 2 O) 6 2+ ---> Fe(OH) 2 + 3H + + 3H 2 O K sp = [Fe 2+ ][OH - ] 2 ≈ 10 -15 M [Fe 2+ ] = 10 -15 /[OH - ] 2 At pH 7.0, [Fe 2+ ] = 10 -15 /(10 -7 ) 2 = 0.08 M

15. Heterotrophic origin for life or The Primordial Soup Hypothesis Bioorganic molecules built up by a variety of reactions that precede metabolism

16. Urey-Miller

18. Urey-Miller used a reducing atmosphere Strongly Reducing –H 2 O, CH 4, NH 3 and H 2 Mildly Reducing (Cosmic rays) –CO, N 2, H 2 O and H 2 Oxidizing –CO 2, CO, N 2, H 2 O, CH 4, and H 2

19. Deep Sea Vents as Models for Early Pre-Biotic Environments

20. Vent Effluent CO 2, CO, N 2, H 2 O, H 2 S, CH 4, and NH 3 Plus plenty of metals IRON!!!!!!!

21. What about outer space? Comets –CO 2, CO, H 2 O, CH 3 OH and NH 3 –Stellar UV and cosmic rays

22. Prebiotic Synthesis of Biomonomers

23. Problems? High initial [ ] requires [HCN] = 0.01M requires [H 2 CO] = 0.01M Must evolve metabolism before soup is depleted Adenine from cyanide Ribose from formaldehyde

24. We don’t know the composition of the early atmosphere Many important compounds have not YET been synthesized under simulated conditions Many ancient life forms (by phylogeny) are autotrophic and hyperthermophilic

25. What about an autotrophic origin? Autotrophy = synthesizing complex organics from simple inorganic molecules

26. Chemolithoautotrophs Use inorganic molecules as an energy source Beggiatoa oxidize sulfide to reduce carbon in the dark

27. Pyrite HCO 3 - + Fe(II)S + H 2 SHCOO - + Fe(IV)S 2 (pyrite) + H 2 O ∆G = -37.1 kJ mol-1 Ethyne to ethane Nitrate to ammonia

28. Importance of FeS clusters in central metabolism (aconitase, succinate dehydrogenase, etc…) The Iron/Sulfur World

29. Three extant ways of CO 2 fixation Reverse TCA (bacteria) Calvin cycle (plants, bacteria) Acetyl-CoA synthase (bacteria)

30. After Chemical Evolution What Next? Replicators

31. A Replicator Replicates It recognizes its components and uses them to makes copies of itself It is subject to the laws of natural selection and must compete with other replicators for resources Success is governed by its –Fidelity –Fecundity –Longevity –Evolvability

32. A Replicator Replicates X X 2X+ X X X X X X X X 2 X X

33. Fidelity Must make accurate copies. Otherwise the copy will not have the properties that made the original such as success

34. Fecundity Must replicate at a high enough rate so that it can out-breed its competitors. Replication is a constant competition with other replicators for limited building blocks

35. Longevity A replicator must be stable and long- lived enough so that it has a chance to replicate. Unstable replicators are unlikely to be able to compete.

36. Evolvability? The ability to adapt to environmental changes

37. Pre-cellular replicator would need to catalyze its own replication Need a molecule that: –Act as a biochemical catalyst to make starting material –Act as a template to replicate itself

38. What about RNA? Guanine UracilAdenine Cytosine PURINES PYRIMIDINES Can recognize itself

39. Ribonucleic Acids Can fold into complex structures

40. RNA can act as an information molecule and an enzyme Certain RNA molecules can “edit” themselves by self-splicing mechanisms

41. Self-splicing

42. Template driven synthesis!

43. RNA molecules have been selected that catalyze many reactions RNA cleavage RNA ligation RNA phosphorylation Phosphodiester cleavage Cyclic PO 4 hydrolysis Amino acid activation tRNA charging Template driven RNA polymerization Porphyrin metallation Glycosidic bond formation Peptide bond formation

44. RNA could have independently replicated itself RNA evolution can be demonstrated in vitro

45. The RNA World