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Introduction

On Life and Chemistry…..

• “Living things are composed of lifeless molecules” (Albert Lehninger) • “Chemistry is the logic of biological phenomena” (Garrett and Grisham)

Distinctive Properties of Living Systems
• Organisms are complicated and highly organized • Biological structures serve functional purposes • Living systems are actively engaged in energy transformations • Living systems have a remarkable capacity for self-replication

A Biomolecular Hierarchy
Simple Molecules are the Units for Building Complex Structures • • • • Metabolites and Macromolecules Organelles Membranes The Unit of Life is the Cell

Molecular organization in the cell is a hierarchy.

Chemistry 40 (Summer 2007)

Properties of Biomolecules Reflect Their Fitness to the Living Condition

• Macromolecules and Their Building Blocks Have a “Sense” or Directionality • Macromolecules are Informational • Biomolecules Have Characteristic ThreeDimensional Architecture • Weak Forces Maintain Biological Structure and Determine Biomolecular Interactions

Chemistry 40 (Summer 2007)

The sequence of monomeric units in a biological polymer has the potential to contain information if the diversity and order of the units are not overly simple or repetitive. Nucleic acids and proteins are information-rich molecules; polysaccharides are not.

IN008

Chemistry 40 (Summer 2007)

Properties of Biomolecules Reflect Their Fitness to the Living Condition

• • • •

van der Waals: 0.4-4.0 kJ/mole Hydrogen bonds: 12-30 kJ/mole Ionic bonds: 20 kJ/mole Hydrophobic interactions: <40 kJ/mole

Chemistry 40 (Summer 2007)

Organization and Structure of Cells

• Prokaryotic cells – A single (plasma) membrane – no nucleus or organelles • Eukaryotic cells – much larger in size than prokaryotes – 103-104 times larger! – Nucleus plus many organelles – ER, Golgi, mitochondria, etc.

Methods for Separating and Purifying Biomolecules
• Salt fractionation (precipitation of proteins with ammonium sulfate) • Chromatography – paper, ion-exchange, affinity, thin-layer, gas-liquid, high pressure liquid, gel filtration • Electrophoresis – paper, high voltage, agarose, cellulose acetate, starch gel, polyacrylamide gel, SDS-PAGE • Ultracentrifugation

Methods for Determining Biomolecular Structures
• Elemental analysis • UV-VIS, IR, NMR spectroscopy • Acid/base hydrolysis • Enzymatic degradation • MS • Specific sequencing methods • X-ray crystallography

Preparations for Studying Biochemical Processes
• Whole animal (transgenic and with gene knockout) • Isolated perfused organ • Tissue slice • Whole cells • Homogenate • Isolated cell organelles • Subfractionation of organelles • Purified metabolites and enzymes • Isolated genes (PCR and site-directed mutagenesis)

Major Causes of Diseases
All of the causes listed act by influencing the various biochemical mechanisms in the cell or in the body.

• Physical agents – mechanical trauma, extremes of T, sudden changes in atmospheric P, radiation, electric shock

• Chemical agents, including drugs: certain toxic compounds, therapeutic drugs, etc. • Biologic agents: viruses, bacteria, fungi, higher forms of parasites

Major Causes of Diseases
• Oxygen lack: loss of blood supply, depletion of the oxygen carrying capacity of the blood, poisoning of the oxidative enzymes • Genetic disorders – congenital, molecular • Immunologic reactions – anaphylaxis, autoimmune disease • Nutritional imbalances – deficiencies, excesses • Endocrine imbalances – hormonal deficiencies, excesses

Water

What Are the Properties of Water?
• High b.p., m.p., heat of vaporization, surface tension • Bent structure makes it polar • Non-tetrahedral bond angles • H-bond donor and acceptor • Potential to form four H-bonds per water

The Solvent Properties of Water Derive from Its Polar Nature

• Ions are always hydrated in water and carry around a "hydration shell" • Water forms H-bonds with polar solutes • Hydrophobic interactions - a "secret of life"

Hydration shells surrounding ions in solution. Water molecules orient so that the electrical charge on the ion is sequestered by the water dipole. For positive ions (cations), the partially negative oxygen atom of H2O is toward the ion in solution. Negatively charged ions (anions) attract the partially positive hydrogen atoms of water in creating their hydration shells.

Chemistry 40 (Summer 2007)

Hydrophobic Interactions
• A nonpolar solute "organizes" water • The H-bond network of water reorganizes to accommodate the nonpolar solute • This is an increase in "order" of water • This is a decrease in ENTROPY

Formation of a clathrate structure by water molecules surrounding a hydrophobicChemistry 40 (Summer 2007) solute.

Acid-base Equilibria
The pH Scale • A convenient means of writing small concentrations: • pH = -log10 [H+] • If [H+] = 1 x 10 -7 M • Then pH = 7

Dissociation of Weak Electrolytes

Consider a weak acid, HA • The acid dissociation constant is given by: • HA → H+ + A• Ka = [ H + ] [ A - ]
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[HA]

The Henderson-Hasselbalch Equation

For any acid HA, the relationship between the pKa, the concentrations existing at equilibrium and the solution pH is given by: • pH = pKa + log10 [A¯ ]
[HA]

Consider the Dissociation of Acetic Acid
Assume 0.1 eq base has been added to a fully protonated solution of acetic acid The Henderson-Hasselbalch equation can be used to calculate the pH of the solution: With 0.1 eq OH¯ added: •pH = pKa + log10 [0.1] [0.9] •pH = 4.76 + (-0.95) •pH = 3.81

Consider the Dissociation of Acetic Acid

• Another case.... • What happens if exactly 0.5 eq of base is added to a solution of the fully protonated acetic acid? • With 0.5 eq OH¯ added: • pH = pKa + log10 [0.5] [0.5] • pH = 4.76 + 0 • pH = 4.76 = pKa

Consider the Dissociation of Acetic Acid
A final case to consider.... What is the pH if 0.9 eq of base is added to a solution of the fully protonated acid? With 0.9 eq OH¯ added: pH = pKa + log10 [0.9] [0.1] pH = 4.76 + 0.95 pH = 5.71

The titration curve for phosphoric acid. The chemical formulas show the prevailing ionic species present at various pH values. Phosphoric acid (H3PO4) has three titratable hydrogens and therefore three midpoints are seen: at pH 2.15 (pK1), pH 7.20 (pK2), and pH 12.4 (pK3).

Chemistry 40 (Summer 2007)

What Are Buffers, and What Do They Do?

• Buffers are solutions that resist changes in pH as acid and base are added • Most buffers consist of a weak acid and its conjugate base • Buffers can only be used reliably within a pH unit of their pKa