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Bioorganic Chemistry and
Biochemistry
CHM3218 Summer C 2008
Dr. Lyons office hours
[email protected]
846-3392
T,W 3-4 PM, R 9-10 AM
Class website
http://www.chem.ufl.edu/~lyons/
Test Dates
May 27
June 17
July 11
July 25
August 8
Biochemistry is more than organic chemistry
Questionably essential
Toxic
Medically important
24
Cr
Bulk
Hydrogen
Carbon
Nitrogen
Oxygen
Sodium
Magnesium
Phosphorous
Sulfur
Chlorine
Potassium
Calcium
Essential
Trace
Manganese
Iron
Cobalt
Nickel
Copper
Zinc
Molybdenum
Selenium
Iodine
Other Elements
Silicon
Vanadium
Boron
Environment is the key to understanding biological systems
Iron as a case study
Geochemical considerations are critical for life
Effect of O2 concentration on other elements
Effect of O2 concentration on other elements
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
Heterotrophic origin for life
or
The Primordial Soup
Hypothesis
Bioorganic molecules built up by a variety of
reactions that precede metabolism
Urey-Miller
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
Deep Sea Vents as Models for Early Pre-Biotic Environments
Vent Effluent
CO2, CO, N2, H2O, H2S, CH4, and NH3
Plus plenty of metals
IRON!!!!!!!
What about outer space?
Comets
– CO2, CO, H2O, CH3OH and NH3
– Stellar UV and cosmic rays
Prebiotic Synthesis of
Biomonomers
Problems?
• Adenine from cyanide
• Ribose from formaldehyde
• High initial [ ]
• requires [HCN] = 0.01M
• requires [H2CO] = 0.01M
• Must evolve metabolism
before soup is depleted
• 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
What about an autotrophic origin?
Autotrophy = synthesizing complex
organics from simple inorganic
molecules
Chemolithoautotrophs
Use inorganic molecules as an energy source
Beggiatoa oxidize sulfide to reduce carbon in the dark
Pyrite
HCO3- + Fe(II)S + H2S
HCOO- + Fe(IV)S2 (pyrite) + H2O
∆G = -37.1 kJ mol-1
• Ethyne to ethane
• Nitrate to ammonia
The Iron/Sulfur World
Importance of FeS clusters in central
metabolism (aconitase, succinate
dehydrogenase, etc…)
Three extant ways of CO2 fixation
• Reverse TCA (bacteria)
• Calvin cycle (plants, bacteria)
• Acetyl-CoA synthase (bacteria)
After Chemical Evolution
What Next?
Replicators
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
A Replicator Replicates
X
X
+
2X
X X
X X
X X
X X
2
X
X
Fidelity
Must make accurate copies. Otherwise
the copy will not have the properties
that made the original such as
success
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
Longevity
A replicator must be stable and longlived enough so that it has a chance
to replicate. Unstable replicators are
unlikely to be able to compete.
Evolvability?
The ability to adapt to environmental
changes
• 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
What about RNA?
Can recognize itself
H
N
N
BASE
N
H
O
N
Ribose
N
H
N
N
Ribose
HO
O
Adenine
O
Uracil
H
H
H
O
N
H
H
N
H
OH
OH
N
N
Ribose
H
N
N
N
N
H
O
Ribose
H
Guanine
PURINES
Cytosine
PYRIMIDINES
Ribonucleic Acids
Can fold into complex
structures
RNA can act as an information
molecule and an enzyme
Certain RNA
molecules can
“edit”
themselves by
self-splicing
mechanisms
Self-splicing
Template driven synthesis!
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
RNA could have
independently replicated
itself
• RNA evolution can be
demonstrated in vitro
The RNA World