Bioorganic Chemistry and Biochemistry CHM3218 Summer C 2008

1. Bioorganic Chemistry and BiochemistryCHM3218 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 Questionably essential Toxic Medically important 24 Cr

4. EssentialTrace Bulk Hydrogen Carbon Nitrogen Oxygen Sodium Magnesium Phosphorous Sulfur Chlorine Potassium Calcium Manganese IronCobalt Nickel Copper Zinc Molybdenum Selenium Iodine

5. Other Elements Silicon Vanadium Boron

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

7. Geochemical considerations are critical for life

12. Effect of O2 concentration on other elements

13. Effect of O2 concentration on other elements

14. Iron as a Case Study Fe(H2O)63+ ---> Fe(OH)3 + 3H+ + 3H2O Ksp = [Fe3+][OH-]3 ≈ 10-38 M [Fe3+] = 10-38/[OH-]3 At pH 7.0, [Fe3+] = 10-38/(10-7)3 = 10-17 M Fe(H2O)62+ ---> Fe(OH)2 + 3H+ + 3H2O Ksp = [Fe2+][OH-]2 ≈ 10-15 M [Fe2+] = 10-15/[OH-]2 At pH 7.0, [Fe2+] = 10-15/(10-7)2 = 0.08 M

15. Heterotrophic origin for lifeorThe 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 • H2O, CH4, NH3 and H2 • Mildly Reducing (Cosmic rays) • CO, N2, H2O and H2 • Oxidizing • CO2, CO, N2, H2O, CH4, and H2

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

20. Vent Effluent CO2, CO, N2, H2O, H2S, CH4, and NH3 Plus plenty of metals IRON!!!!!!!

21. What about outer space? Comets • CO2, CO, H2O, CH3OH and NH3 • Stellar UV and cosmic rays

22. Prebiotic Synthesis of Biomonomers

23. Problems? • Adenine from cyanide • Ribose from formaldehyde • High initial [ ] • requires [HCN] = 0.01M • requires [H2CO] = 0.01M • Must evolve metabolism before soup is depleted

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. Ethyne to ethane • Nitrate to ammonia Pyrite HCO3- + Fe(II)S + H2S HCOO- + Fe(IV)S2 (pyrite) + H2O ∆G = -37.1 kJ mol-1

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

29. Three extant ways of CO2 fixation • Reverse TCA (bacteria) • Calvin cycle (plants, bacteria) • Acetyl-CoA synthase (bacteria)

30. After Chemical EvolutionWhat 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 X X X X + 2X 2 X X X X 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? Can recognize itself Adenine Uracil Cytosine Guanine PYRIMIDINES PURINES

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 PO4 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