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). Biological Macromolecules Thousands of atoms Proteins
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)
Thousands of atoms
Building Block Organic Molecules
Tens of atoms
A few atoms
20 different types of amino acids (different R groups)
polymers called polypeptides or proteins
The simplest amino acid
Building up the simpler amino acids
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
Folding dependent on sequence
Aldolase with substrate bound
Actin fibres - cytoskeleton
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.
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
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.
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).
Catalytic RNAs (ribozymes) are known – both natural and synthetic
Part of Group II intron structure
Simple fatty acids
Amphiphiles = polar head + hydrophobic tail
Typical phospholipid in a modern cell membrane
Fluid and Flexible
Began with a mixture of CH4 , NH3, H2O and H2.
Energy source = electric spark or UV light.
Obtained 10 amino acids.
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)
What were conditions on early Earth? Atmosphere?
Where was the chemistry happening?
Could everything form at the same time?
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.
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
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
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)
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....
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
concentrations normalized relative to Gly
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/
The early group are simpler and are thermodynamically less costly
The late group are more complex and are more thermodynamically costly
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
Norvaline? - don’t know
Homoserine? - lactonization