1. Chemistry of Life What are the important molecules in cells? What do they do? Why are these particular molecules used? Could other molecules do the job just as well? How / where were these molecules formed? (prebiotic synthesis)

2. Small Molecules A few atoms CO 2 H 2 O NH 3, N 2 Building Block Organic Molecules Tens of atoms Amino acids Sugars Nucleotides Lipids Biological Macromolecules Thousands of atoms Proteins Polysaccharides Nucleic Acids Prebiotic chemistryPolymerization

3. Building Blocks 1 - Amino acids 20 different types of amino acids (different R groups) peptide bond polymers called polypeptides or proteins

4. The simplest amino acid Glycine Gly G Building up the simpler amino acids Alanine Ala A Valine Val V Leucine Leu L Isoleucine Ile I Serine Ser S Threonine Thr T Aspartic acid Asp D Glutamic acid Glu E Hydrophobic Hydrophilic Acidic Proline pro P

5. More complex amino acids Asparagine Asn N Glutamine Glu Q Lysine Lys K Arginine Arg R Histidine His H Phenylalanine Phe F Tyrosine Tyr Y Tryptophan Trp W Cysteine Cys C Methionine Met M Amines Hydrophilic Basic Aromatic Hydrophobic Sulphur containing

6. Protein function - enzymes Aldolase with substrate bound Enzymes are catalysts of specific chemical reactions. Enzymes control metabolism Why use proteins as catalysts? Versatile set of chemical groups Active sites. Substrate binding. Transition states Specific structures Folding dependent on sequence

7. Structural proteins – e.g. collagen fibres in joints Actin fibres - cytoskeleton

8. Protein dynamics – e.g. actin/myosin in muscles chemical energy => work ATP synthase in mitochondria and bacteria A proton gradient across the membrane (created by electron transport chain) causes drives the motor to turn and drives synthesis of ATP. Storage of chemical energy. Gee whizz!

9. What can’t proteins do?Replication. Information Storage. Heredity Central dogma: DNA to RNA to proteins. Amino acids may be easy to form by prebiotic synthesis but proteins as we know them can only exist after the evolution of translation and the genetic code. RNA world theory (to be discussed later) – RNAs for both catalysis and information storage. Cellular organisms always use DNA for information storage. Viruses can use RNA or DNA Exception? Prion proteins: Does this count as replication? Normal form Scrapie form

10. Building blocks 2 – Sugars Glucose is a 6-carbon sugar. Sugars can assemble to form polymers (starch, cellulose….) Ribose and Deoxyribose are 5-carbon sugars. Function: Metabolism. Energy storage. Structural roles. Neither catalysis nor information storage.

11. Building blocks 3 - Nucleotides

12. Nucleic acids can store information Double stranded DNA. Both strands contain information to make the other. Single stranded RNA. Two-stage replication: plus to minus to plus (viruses). Nucleic acids are polymers composed of nucleotides.

13. Part of Group II intron structure RNA can also fold to complex 3d structures Catalytic RNAs (ribozymes) are known – both natural and synthetic

14. Building blocks 4 – Lipids Simple fatty acids Amphiphiles = polar head + hydrophobic tail Typical phospholipid in a modern cell membrane

15. Lipids Self-assembly Micelles Bilayers Cell membrane Fluid and Flexible Compartmentalization Selectively permeable

16. Prebiotic synthesis of organic molecules Miller-Urey experiment (1953) Began with a mixture of CH 4, NH 3, H 2 O and H 2. Energy source = electric spark or UV light. Obtained 10 amino acids. Soup recipe!

17. Prebiotic synthesis Begin with simple molecules thought to be common on early Earth Use reaction conditions thought to exist on early Earth Show that biomolecules are synthesized Syntheses have been found for most of the building block molecules. Purines can be built up from HCN Sugars can be built up from CH 2 O (formaldehyde ) Issues: What were conditions on early Earth? Atmosphere? Where was the chemistry happening? Could everything form at the same time? Concentration? Stability?

18. Atmospheres and Chemistry reducing: CH 4, NH 3, H 2 O, H 2. or CO 2, N 2, H 2 or CO, N 2, H 2 There is hydrogen gas and/or hydrogen is present combined with other elements (methane, ammonia, water) neutral: CO or CO 2, N 2, H 2 O no hydrogen or oxygen gas oxidizing: O 2, CO 2, N 2 oxygen gas present Prebiotic chemists favour reducing atmospheres. Yields in Miller-Urey exp are higher and more diverse in reducing than in neutral atmospheres. Doesn’t work in oxidizing atmosphere.

19. Planetary Atmospheres Major element in universe is H (big bang) so doesn’t it make sense that atmosphere was reducing? Jupiter retains original mixture: H 2, He + small amounts CH 4, NH 3, H 2 O Smaller planets lose H 2 New atmosphere created by outgassing from interior Geologists & Astronomers favour an intermediate atmosphere. (i)Venus - 64 Earth atmospheres pressure! Mostly CO 2 and N 2 (ii)Carbonates in sedimentary rocks on Earth suggest previously lots of CO 2 Current Earth: Mostly N 2, O 2 + small amounts of CO 2 H 2 O – changed by life. Mars: very low pressure – mostly CO 2 and N 2 So maybe Miller and Urey were wrong? :-(

20. Alternative suggestion – Hydrothermal vents Sea water passes through vents. Heated to 350 o C. Cools to 2 o C in surrounding ocean. Supply of H 2 H 2 S etc. Fierce debate as to whether these conditions favour formation or breakup of organic molecules (Miller & Lazcano, 1995)

21. Organic compounds in meteorites Most widely studied meteorite is the Murchison meteorite. Fell in Australia in 1969. Carbonaceous chondrite. Contained both biological and non-biological amino acids Both optical isomers (later shown to be not quite equal) Compounds are not contamination Just about all the building block molecules have now been found in carbonaceous meteorites (Sephton, 2002). Astrochemistry: molecular clouds; icy grains; parent bodies of meteorites.... Delivery by: dust particles; meteorites; comets....

22. What to make of all this....? If we believe in a heterotrophic origin of life, organic molecule supply is crucial. Observation of organic molecules in meteorites and in space suggests that the chemistry does work! What were the relative amounts synthesized on Earth and delivered from space? Maybe delivery from space is very minor but the meteorites are telling us about the chemistry that was happening on Earth at the same time. Maybe delivery from space is a large part. But the same molecules are supplied as are required by the heterotrophic theory. Hydrothermal synthesis seems less well documented, and is also rather ‘local’.... Heterotrophic/autotrophic issue still not resolved...(more later)

23. Comparison of amino acid frequencies produced non-biologically 10 amino acids are found in the Miller-Urey experiments. Very similar ones are also found in meteorites (Murchison and Yamato), an Ice grain analogue experiment, and other places. Maybe these are ‘early’ amino acids that were available for use by the first organisms. The other 10 are not seen. Maybe these are ‘late’ amino acids that were only used when organisms evolved a means of synthesizing them biochemically. Higgs & Pudritz : http://www.physics.mcmaster.ca/~odonnedv/OIbook/ concentrations normalized relative to Gly

24. Glycine Gly G The early group are simpler and are thermodynamically less costly Alanine Ala A Valine Val V Leucine Leu L Isoleucine Ile I Serine Ser S Threonine Thr T Aspartic acid Asp D Glutamic acid Glu E Hydrophobic Hydrophilic Acidic Proline pro P

25. The late group are more complex and are more thermodynamically costly Asparagine Asn N Glutamine Glu Q Lysine Lys K Arginine Arg R Histidine His H Phenylalanine Phe F Tyrosine Tyr Y Tryptophan Trp W Cysteine Cys C Methionine Met M Amines Hydrophilic Basic Aromatic Hydrophobic Sulphur containing

26. Why are there only 20 amino acids? Weber and Miller (1981) Only  amino acids not  and  Always one  hydrogen Some non-biological amino acids are found in meteorites and Miller- Urey exp with concentrations as high as the biological ones examples: Norvaline? - don’t know Homoserine? - lactonization