Foundations of Biochemistry

Doba Jackson, Ph.D.

Dept. of Chemistry & Biochemistry

Huntingdon College

What distinguishes living organisms from other forms of matter?

• High degree of chemical complexity and organization (muscle tissue)

• System for extracting energy from the environment (bird)

• The ability to self-replicate (zebra)

• Ability to sense changes in the surroundings and respond

• Defined functions of each component and regulated interactions

• The ability to adapt with time (evolution)

Chemical Foundations

“What are the common chemical principals important to all cells”

Only 30 of the 90 naturally occuring elements are found

in biological systems

Components of macromolecules: the ABC’s

of BiochemistryProteins Nucleic Acids Lipids

Carbohydrates

You must remember all of these functional groups!!!!!

Biomolecules are hydrocarbons with attached

functional groups

What do these have in common?

Hydrocarbons

What do these have in common?

All have carbon-oxygen bonds

What do these have in common?

All have carbon-nitrogen bonds

What do these have in common?

All have carbon-sulfur bonds

What do these have in common?

All have carbon-phosphate bonds

Some Definitions

• Chiral center- a carbon atom with four different a substituents (ie.- asymmetric carbon)

• Enantiomers- pairs of stereoisomers that are mirror images of each other.

• Diastereomers- pairs of stereoisomers that are not mirror images of each other.

4 substituents 3 substituents

Enantiomers Same molecule

Example: 2,3 disubstituted butanes

Stereoisomers distinguisable by taste

Aspartate

Phenylalanine

Summary of chemical foundations

• Only 30 of the 90 naturally occuring elements are found in biological systems

• 99.9% of biomolecules are considered organic compounds

• Most biomolecules have more than one functional group

• Conformation, configuration, and constitution are all important factors for determination of biological activity

Aqueous SolutionsBy Doba D. Jackson, Ph.D.

Dept. of Chemistry & BiochemistryHuntingdon College

Why study Water

• Water is the most abundant chemical in living systems making up to 70% of the mass of most organisms.

• The attractive forces between water molecules and the slight tendency of water molecules to ionize are of crucial importance to the structure and function of biomolecules.

Outline of Discussion

• Weak interactions in aqueous solution– Hydrogen Bond– Nonpolar compounds and water insolubility– Hydrophobic interactions, van Der waals interactions

• Ionization of water, weak acids and bases– Review acids, bases, Kw and pKa

• Buffers, pH changes in biological systems– Phosphate, Carbonate buffers in living organisms– Tris, HEPES buffers commonly used in laboratories

Structure of a water molecule

Less than 109.5º

- The Oxygen bears two partial negative charges each aligned with the p-orbitals.

- Each Hydrogen bears a positive charge

aligned 104.5º from the OH bond.

The Hydrogen Bond

“I believe that as the methods of Structural chemistry (x-ray crystallography) are further applied to physiological problems, it will be found that the significance of thehydrogen bond for physiology is greater than that of any other single structural feature” -Linus Pauling, The Nature of the Chemical Bond (1939)

The Hydrogen Bond

- The hydrogen atom becomes between covalently bound oxygen and the oxygen aligned from its neighbor.

- The hydrogen bond has a dissociation energy of 23 kJ/mol (compared to 470 kJ/mol).

- Based on orbital overlap, the hydrogen

bond is 10% covalent and 90% electrostatic.

- The total hydrogen bond length is

approximately 2.8 Ǻ (~ 3 Ǻ).

Hydrogen bonding in ice

- Solid ice

2 covalent bonds 4 hydrogen bonds 6 total bonds

- Liquid water

2 covalent bonds 2.4 hydrogen bonds 4.4 total bonds

Hydrogen Bonds other than water

Any electronegative atom (usually N, O) with a pair of electrons can attract a hydrogen attached to another electronegative atom.

Examples of Biologically important hydrogen bonds

Alcohol & water

Ketone & water

Between amino acids in proteins DNA

strands

Water as a solvent

- Polar solutes: compounds that have polar bonds; usually dissolve easily in water.

- Nonpolar solutes: compounds that do not have polar bonds; usually difficult to dissolve in water but dissolves easily in nonpolar solvents (hexane, chloroform or benzene).

- Amphipathic solutes: compounds with polar and nonpolar groups; solubility will vary.

– Water at a hydrophobic surface loses a hydrogen bond.

– Water molecules compensate for this by creating a low-density water network with lower entropy directly surrounding the hydrophobic solute.

– Water covers the surface with clathrate-like hexagons, so avoiding the loss of most of the hydrogen bonds.

What happens to the structure of water at a hydrophobic

interface?

Hydrophobic Effect

Release of ordered water can drive the formation of an enzyme-

substrate complex

Review weak (noncovalent) molecular interactions

• Electrostatic (ionic) interactions- The attractive forces between oppositely charges molecules or functional groups.

• Hydrogen Bonds- an interaction between a hydrogen covalently attached to an electronegative atom and the electron pair of another electronegative atom.

• Hydrophobic interactions- the strong tendency of water to minimize the surface area surrounding nonpolar groups or molecules.

• Van der Waals forces- are the result of induced electrical interactions of closely approaching atoms as their negative electron clouds fluctuate with time.

Van der Waals forces

Van der Waals forces .4 – 4.0 .3 - .6

Hydrogen bonds 12 – 30 .3

Ionic interactions 20 .25

Hydrophobic interactions

<40 >1

Strength(kJ/mol)

Distance(nm)

Weak chemical forces and their strengths and distances

Hydrophobic interactions can act across very large distances which makes these interactions very dominant

in determining macromolecular structure and function

strength

“Proton hopping” common in enzymes that translocate protons

across cell membranes

Cytochrome f; in photosynthesis

Weak interactions are crucial to macromolecular structure and function

• For macromolecules (DNA, RNA & proteins) the most stable structure is one that maximizes the weak bonding possibilities.

Titration curves can reveal dissociation constants (pKa) and buffer ranges

Henderson-Hasselbalch Equation: relationship between pH, pKa and buffer concentrationsCH3COOH CH3COO- + H+

3

3

3

3

3

3

3

3

3

3

a

a

a

a a

a

a

CH COO H

CH COOH

CH COO HLog K Log

CH COOH

CH COOLog K Log Log H

CH COOH

pK Log K

pH Log H

CH COOpK Log pH

CH COOH

CH COOpH pK Log

CH COOH

K

Typically a buffer is best when it is within .5 units of

its pKa

Blood, Lungs and extracellular fluid is

buffered by carbonateVigorous Exercise(lactic acid)

Blood, extracellular Fluid

Lungs, Air space

Vigorous Exercise

Typical catabolismraises pH

Typical catabolismraises pH

Enzymes have specific pH optimums due to the combination of many

functional groups