Proteins and Membranes

Lecture 3: The Amino Acids

Amino Acid Structure
Amino acids are the building blocks for proteins
A central α carbon atom is attached to: a carboxyl group (COOH)
an amino acid
a hydrogen atom
a side chain
All 20 AA have this same structure but their side chains vary in; size, shape, charge, hydrophobicity and reactivity
The structure of this side chain is important in terms of that specific amino acid and the role it will then play in that
specific polypeptide chain, and ultimately the functionality of the protein it is a part of
- (eg. Where it will be found, if it is part of an active site, whether it is hydrophobic, part of a water channel,
charged, etc)

Amino acids are ionised in the cell

- Ionisation = the process by which an atom or a molecule acquires a positive or negative charge
- Hydrogen atoms are donated by ACIDS and accepted by BASES
- Amino acids have both basic and acidic properties – that characteristic is called amphoteric
- In a typical cell, the pH ~7.5 (this is called the physiological pH and is the pH pf a cystole)
- Different compartments inside the cell can vary in terms of their pH
- so the amino acids will be influenced and have a slightly different functionality in compartments of different pHs
- At physiological pH amino acids are zwitterions where the amino group is protonated and the carboxyl group is
deprotonated.
- Some side chains are also ionisable
Importance for Intermolecular interactions
- The ability to donate and accept hydrogens in these different groups has an important impact on whether or not it
can have or create hydrogen bonds.
- The amino group is an H-bond donor, and the carboxyl group is an H-bond acceptor

The Relationship between pH & Keq of an ACID/BASE system

- Molecules used by cells have multiple acidic or basic groups.
- Acidic groups will donate protons or donate their electrons depending on numerous things, the biggest thing being the
pH of its surrounding environment.
- Its important to understand the properties/state of dissociation of groups at different pH values/
- We can do this by looking at the ACID/BASE system.
- Dissociation of an acid group: HA ⇌ H+ + A=
- The equilibrium constant (Kacid) is equal to the concentration of products over the concentration of reactant\
- Ka = [H+] [A-]
[HA]
where, Ka = the acid dissociation constant
K = extent of which reactions become products

How do we get the Henderson=Hasselbach equations?

pH = pKa + log [A-]
[HA]

This equation helps us to understand the relationship between our dissociation constant (pKa) and pH, and the effect of
pH on how this dissociates into half of the product [A-] / [HA]

* The lower the pKa the stronger the acid.

A strong acid will give up it protons readily.
HH only really suitable for weak acids.

Ionisation of Amino Acids

The pKa value Xn tell us how a molecule or its side chain will behave at a certain pH
The carboxyl group and the amino group are ionisable.
The pKa is the pH at which the groups are ~50 % ionised.
- pKa of the carboxyl group is ~2. (So at pH 2 about ½ the groups will be ionised
- pKa of the amine group is ~ 9.5 (So at pH 9.5 about ½ the groups will be ionised
If you know the particular pKa of a particular group ad you know the pH of its system, you can see if it is going to be
protonated or deprotonated.

Eg. A polypeptide with 12 amino acids with side chains that have a pKa OF 8
If you put this chain in a pH of 8, 50% will be ionised
6 HA & 6 A- and H+
Ionisable groups are protonated when the pH is before pKa
They are not protonated when pH is above pKa
Ionisation when pH and pKa are >1 unit apart.

Using Henderson-Hasselbach
pKa of X = 7.15, what percentage of X is ionised at pH 7.5 ?

First an approximation – pKa is the pH at which 50% of the weak acid will be ionised.

At pH 7.5 will ionisation be > or < 50%?

* Remember to make it clear that unprotonated is 69% and therefore protonated is 31% 1/3.24

AMINO ACIDS
Classifying Amino Acids
- There are atleast 250 different amino acids
- Proteins built from repertoire of 20 ‘common’ amino acids
- Side chains differ in; size, hydrophobicity, charge and H-bonding capacity.
- Amino acids can be split into – Hydrophobic (uncharged and insoluble) and hydrophilic (charged and soluble)
- Both of which can be further subdivided

Hydrophilic (water soluble)

- Charged and polar side chains
- Found at water/protein interface
- Determine solubility of a protein
- Provide binding sites for charged molecules protein
- SPLIT INTO:
- BASIC: Histidine, Lysine, Arginine
- ACIDIC: Aspartate and Glutamate
- POLAR: Threonine, Glutamine, Asparagine, Serine

Hydrophobic (water insoluble)

- Uncharged and nonpolar side chains
- Found in the interior of proteins
- At the interface of protein and hydrophobic molecules such as the cone of lipid membranes
- SPLIT INTO
- ALPHATIC: Isoleucine, Alanine, Valine, Leucine, Methionine
- AROMATIC: Phenylalanine, Tryptophan, Tyrosine
- SPECIAL: Proline, Glycine, Cystine

Mnemonics
LICS: basic, acidic, polar bears
BIC: sp, ar, alph

BASIC Hos Kill Realism

ACIDIC Dental Erosion
POLAR Trackers Query Nautical Speeds
ALO Is A Violent Little Minx
AROMATIC Flowers Were Yellow
SPECIAL People Grow Cacti