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 27June 17July 11July 25

August 8

Biochemistry is more than organic chemistry

Medically importantToxic

Questionably essential

Cr24

Bulk

HydrogenCarbon

NitrogenOxygenSodium

MagnesiumPhosphorous

SulfurChlorine

PotassiumCalcium

ManganeseIron

CobaltNickel

CopperZinc

MolybdenumSelenium

Iodine

EssentialTrace

Other Elements

Boron

Silicon

Vanadium

Environment is the key to understanding biological systemsIron 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 lifeor

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?

• High initial [ ]

• requires [HCN] = 0.01M

• requires [H2CO] = 0.01M

• Must evolve metabolism

before soup is depleted

• Adenine from cyanide

• Ribose from formaldehyde

• 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

Importance of FeS clusters in central metabolism (aconitase, succinate

dehydrogenase, etc…)

The Iron/Sulfur World

Three extant ways of CO2 fixation

• Reverse TCA (bacteria)• Calvin cycle (plants, bacteria)• Acetyl-CoA synthase (bacteria)

After Chemical EvolutionWhat 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

X2X+

X

X

X

X

X

X

X

X2X

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?

BASE

O

OHOH

HH

HH

HO

Guanine

UracilAdenine

Cytosine

PURINES PYRIMIDINES

N

N

N

N N

NN

O

O

Ribose

Ribose

H

H

H

N

N

N

O

N

N

N

N O

NRibose

Ribose

H

H

H

H

H

Can recognize itself

Ribonucleic AcidsCan 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