Bioorganic Chemistry and

Biochemistry
CHM3218 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/
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 Essential
Trace
Hydrogen
Carbon
Nitrogen Manganese
Oxygen Iron
Sodium Cobalt
Magnesium Nickel
Phosphorous Copper
Sulfur Zinc
Chlorine Molybdenum
Potassium Selenium
Calcium 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 X X X X
+ 2X 2
X X X X 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 long-

lived 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 H O

N N
BASE Ribose
N
H
N
N Ribose
HO O

O Adenine Uracil
H
H H O
N H N

H H
N
OH OH Ribose
N H N

N N

O Ribose
N H

Guanine Cytosine
PURINES 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