Amino acids and primary structure

Amino acids basic facts

• Monomer units of proteins (primary structure)

• Each AA has a name, normally ending in -ine.

• For convenience, these are often abbreviated E.g. Gly for Glycine

• Essential AA= cannot be made in the body, must be consumed

• Non-essential AA= cannot be made in the body

Chirality of amino acids

• The amino (-NH2) substituents is the “main” one

• When its on the left = L configuration

• When on the right = D configuration

• Other 3 are: H, CH3 and CO2H

4 sub-groups of amino acids

1) Hydrophobic AA with non-polar R groups

• Glycine- no chirality as R group = H

• Proline- found in rigid proteins e.g. collagen

2) Positively charged AA

• Histidine- found in active sites

• Has an imidazole ring= binds and releases H+

3) Polar AA

• e.g.Cysteine, contains an SH group

• Can covalently bond with another Cysteine/itself

4) Negatively charged AA

• e.g. Glutamate, excitatory NT

What are pH and pKa?

PH = H+ concentration

• most bodily fluids 6.5-8pH

Dissociation constant = Ka (Inconvenient)

PKa is a more manageable number, allows for simple comparisons etc.

• AB— A+ and B-

• How readily an acid donates a proton

• Smaller pKa values = stronger acidity e.g. lactic acid = 3.8

• AA can exist in various protonated states = different pKas

If the pH of a solution is the same as the pKa of the AA, 50:50 protonated : deprotonated.

If the pH is lower than pKa = protonated, and pH higher = deprotonated.

How to work out Ka and pKa

Ka = (A+)(B-)/AB.

Where A and B are ions that combine to form an acid.

PKa= -log10Ka

Index of acidity of acids

What are zwitterions?

• Molecules that posses both +ve and -ve charges, so have an overall neutral charge

• Amino acids in a neutral pH solution exist predominantly as dipolar ions (zwitterions)

• Can exist as either unionised or zwitterionic

How does the protonation of a molecule change with pH?

At low pH, the concentration of both groups being protonated is highest.

At middle (neutral) pH, the zwitterionic form is most common

At high pHs deprotonated forms are most common

Peptide bond formation and structure

• Condensation reaction

• A water molecule is released during the formation of a peptide bond as an amine group joins to a carboxylate group (dehydration synthesis)

• The amino end is the beginning of the chain.

• Main chain and side chains vary with molecules

• Backbone = rich in H bonding potential

• Each AA contains a CO double bond = good hydrogen bond acceptor OR NH group = H bonding potential H donor

Arrangement of a peptide bond

• Peptide bonds are planar around the CO group of one AA and the NH group of the other. Typical bond length between = 1.32 Å

• Trans-peptide bonds = alpha C’s on opposite sides

• Cis-peptide bond = alpha C’s on same side

• Almost all are Trans- as it avoids steric clashes (atoms become too close to eachother)