Transcript Slide 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) Small Molecules Building Block Organic Molecules Biological Macromolecules A few atoms Tens of atoms Thousands of atoms CO2 Amino acids H 2O Sugars NH3, N2 Nucleotides Lipids Prebiotic chemistry Proteins Polysaccharides Nucleic Acids Polymerization Building Blocks 1 - Amino acids 20 different types of amino acids (different R groups) peptide bond polymers called polypeptides or proteins Glycine The simplest amino acid Gly G Building up the simpler amino acids Alanine Ala A Valine Val V Aspartic acid Serine Leucine Proline Leu L Hydrophobic Asp D Ser S pro P Isoleucine Threonine Ile I Thr T Glutamic acid Glu E Hydrophilic Acidic More complex amino acids Lysine Phenylalanine Lys K Phe F Asparagine Cysteine Asn N Cys C Glutamine Arginine Tyrosine Arg R Tyr Y Methionine Glu Q Met M Amines Hydrophilic Basic Histidine Tryptophan His H Trp W Aromatic Hydrophobic Sulphur containing Protein function - enzymes 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 Aldolase with substrate bound Structural proteins – e.g. collagen fibres in joints Actin fibres - cytoskeleton 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! 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 Building blocks 2 – Sugars Ribose and Deoxyribose are 5-carbon sugars. Glucose is a 6-carbon sugar. Sugars can assemble to form polymers (starch, cellulose….) Function: Metabolism. Energy storage. Structural roles. Neither catalysis nor information storage. Building blocks 3 - Nucleotides Nucleic acids are polymers composed of nucleotides. 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). RNA can also fold to complex 3d structures Catalytic RNAs (ribozymes) are known – both natural and synthetic Part of Group II intron structure Building blocks 4 – Lipids Simple fatty acids Amphiphiles = polar head + hydrophobic tail Typical phospholipid in a modern cell membrane Lipids Self-assembly Micelles Bilayers Cell membrane Fluid and Flexible Compartmentalization Selectively permeable Prebiotic synthesis of organic molecules Miller-Urey experiment (1953) Began with a mixture of CH4 , NH3, H2O and H2. Energy source = electric spark or UV light. Obtained 10 amino acids. Soup recipe! 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 CH2O (formaldehyde) Issues: What were conditions on early Earth? Atmosphere? Where was the chemistry happening? Could everything form at the same time? Concentration? Stability? Atmospheres and Chemistry reducing: CH4 , NH3, H2O, H2. or CO2, N2, H2 or CO, N2, H2 There is hydrogen gas and/or hydrogen is present combined with other elements (methane, ammonia, water) neutral: CO or CO2 , N2 , H2O no hydrogen or oxygen gas oxidizing: O2, CO2, N2 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. Planetary Atmospheres Major element in universe is H (big bang) so doesn’t it make sense that atmosphere was reducing? Jupiter retains original mixture: H2, He + small amounts CH4, NH3, H2O Smaller planets lose H2 New atmosphere created by outgassing from interior Geologists & Astronomers favour an intermediate atmosphere. (i) Venus - 64 Earth atmospheres pressure! Mostly CO2 and N2 (ii) Carbonates in sedimentary rocks on Earth suggest previously lots of CO2 So maybe Miller and Urey were wrong? :-( Current Earth: Mostly N2, O2 + small amounts of CO2 H2O – changed by life. Mars: very low pressure – mostly CO2 and N2 Alternative suggestion – Hydrothermal vents Sea water passes through vents. Heated to 350o C. Cools to 2o C in surrounding ocean. Supply of H2 H2S etc. Fierce debate as to whether these conditions favour formation or breakup of organic molecules (Miller & Lazcano, 1995) 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.... 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) Comparison of amino acid frequencies produced non-biologically Gly Ala Asp Glu Val Ser Ile Leu Pro Thr Miller 1.000 1.795 0.077 0.018 0.044 0.011 0.011 0.026 0.003 0.002 Murchison Yamato 1.00 1.000 0.34 0.380 0.19 0.035 0.40 0.110 0.19 0.100 0.003 0.13 0.060 0.04 0.035 0.29 0.003 Ice Exp. 1.000 0.293 0.022 0.012 0.072 concentrations normalized relative to Gly 0.001 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/ Glycine The early group are simpler and are thermodynamically less costly Gly G Alanine Ala A Valine Val V Aspartic acid Serine Leucine Proline Leu L Hydrophobic Asp D Ser S pro P Isoleucine Threonine Ile I Thr T Glutamic acid Glu E Hydrophilic Acidic The late group are more complex and are more thermodynamically costly Lysine Phenylalanine Lys K Phe F Asparagine Cysteine Asn N Cys C Glutamine Arginine Tyrosine Arg R Tyr Y Methionine Glu Q Met M Amines Hydrophilic Basic Histidine Tryptophan His H Trp W Aromatic Hydrophobic Sulphur containing 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 MillerUrey exp with concentrations as high as the biological ones examples: Norvaline? - don’t know Homoserine? - lactonization