Amino Acids

Amino acids are the basic structural unit of all proteins. A 'free' amino acid (a single amino acid) always has:

an amino group -NH₂,

a carboxyl group -COOH

a hydrogen -H

a chemical group or side chain -"R".

These are all joined to a central carbon atom, the a -carbon as shown in the diagram below.

Since the amino acids (except glycine) have 4 different groups attached to the a-carbon, they are optically active stereoisomers (recall 23.101 Organic Chemistry) although only L-isomers are found in proteins.

At a neutral pH, both the amino and the carboxyl groups are ionised, giving what is termed the zwitterionic form of the molecule (also called a dipolar ion). This is the form of the amino acid shown in the diagram below.

Types of Amino Acid

In the above diagrams, the "R" represents "a chemical group" and gives each amino acid its distinctive properties.

With amino acids, this chemical group is called the "sidechain", and it specifies the amino acid. There are only 20 different amino acids found in proteins, each with it's own defining sidechain. These sidechains have a widespread range of chemical (e.g.charge etc) and structural (e.g. shape etc) diversity.

Here we can view the amino acids as they are commonly grouped.

ALIPHATIC AMINO ACIDS

Aliphatic amino acids are hydrophobic. They do not like to be in contact with water molecules in an aqueous solution. For this reason, they are often located in the core of the protein, surrounded by the rest of the protein, and "shielded" by them from the aqueous surroundings.

Please press the button as before to obtain an image of the amino acid in the opposite frame. Try and look for differences between them all. It will help if you turn on the "Rotation" function in the Chime pop up menu

Glycine (Gly; G) is the simplest and smallest of all amino acids, and the only one which is not optically active since it has a single hydrogen atom as it's sidechain.	Alanine (Ala; A) has a methyl group as it's sidechain.
Valine (Val; V) has a slightly longer sidechain again, and this time there is a branch. As the aliphatic side chains get longer they are also more hydrophobic.	Leucine (Leu; L) is very similar to Valine execpt it has another methyl group attached to the sidechain.
Isoleucine (Ile; I) is again similar to leucine and valine except that the orientation of the atoms in the sidechain is slightly different. Isoleucine also has two centers of asymmetry.	Proline (Pro; P) is different from al the other amino acids in that the sidechain is bonded to both the a-carbon but also to the amino group. As you will see later, this has marked effects on the architecture of the proteins. And although aliphatic, it does not mind being in contact with water as much as the others.

AROMATIC AMINO ACIDS

These are the amino acids which contain an aromatic ring as part of their sidechains. Because of the hydrophobic nature of aromatic rings these amino acids are highly hydrophobic

Phenylalanine (Phe; F) is the first of all the aromatic amino acids. It contains a phenyl ring attached to a methylene group. Due to the phenyl ring it is a hydrophobic amino acid.	Tyrosine (Tyr; Y) contains a hydroxyl group at the end of the phenyl ring. This makes tyrosine less hydrophobic than phenylalanine. It is also a reactive group, whereas the sidechains so far have all been unreactive.
Tryptophan (Trp; W) has a slightly different ring attached to the methylene group. This is an indole ring and it is highly hydrophobic.

SULPHUR CONTAINING AMINO ACIDS

There are two amino acids which contain a sulphur atom. They are both very special but for completely different reasons.

Cysteine (Cys; C) contains a sulphydryl group (-SH). This is extremely reactive, and can form hydrogen bonds. Cysteine is very important because it can also form disulphide bridges (explained in a later tutorial). Even though the -SH group of cysteine can form hydrogen bonds the long aliphatic part of the side chain makes it quite hydrophobic.

Methionine (Met; M) is a very special amino acid in that it is the "start" amino acid in the process of translation (protein synthesis), and therefore, begins every single protein made. It too has a sulphur atom, bu this time it is in a thioether linkage, and is relatively unreactive. Methionine has a highly hydrophobic sidechain.

HYDROPHILLIC AMINO ACIDS

These amino acids can be split into a several groups. There are those which are neutral, those which are acidic, and those which are basic.

Acidic Amino Acids

These amino acids are highly polar, and are nearly always negatively charged at physiological pH.

Aspartate (Asp; D) is really aspartic acid. It is called aspartate because it is usually negatively charged at physiological pH and so it is named for the carboxylate anion. (Compare acetic acid and acetate.)	Glutamate (Glu; E) is also called glutamic acid. The side chain of glutamate also has a carboxylate group which has a negative charge at physiological pH

Basic Amino Acids

These amino acids contain side chains which are postively charged at physiological pH. The pK_a of Histidine, which is between 6 and 7 in proteins means that it is able to accept or donate proteins at physiological pH. For this reason histidine is often found at the active site of enzymes.

Lysine (Lys; K) has one of the longest side chains of all the amino acids. Although most of the side chain appears to be a hydrophobic hydrocarbon chain it is a very polar because of the terminal amino group and is classified as a hydrophillic amino acid.	Arginine (Arg; R) has in fact the largest of all sidechains Bacause of the guanidino group attached to the sidechain it has a high pKa value and is postively charged at physiological pH.
Histidine (His; H) has an imidazole ring which often sits inside the active site of an enzyme and helps bonds to be broken or made. It can do this because it can exist in two states -uncharged, or positively charged.

Neutral Polar Amino Acids

These amino acids are not charged at physiological pH. However they all have groups on their side-chains which are polar and can form hydrogen bonds. For this reason the amino acids are classed as hydrophillic.

Serine (Ser; S) contains an aliphatic chain with a hydroxyl group. It looks like the hydroxylated version of alanine. The OH group make the amino acid highly reactive and hydrophillic as it readily forms hydrogen bonds.	Threonine (Thr; T) is another neutral amino acid which has a highly reactive (and highly hydrophillic) hydroxyl group. This is an odd amino acid in that it contains two centers of asymmetry (two asymetric carbon atoms). This property is shared only by isoleucine.
Asparagine (Asn; N) is the amide derivative of Aspartic acid. When the carboxylate sidechain is amidated the resulting amide is uncharged. There is a terminal amide group as opposed to the carboxyl group on aspartate. (Click back to aspartate to check if you can't remember).	Glutamine (Gln; Q) is similar to Asparagine, with a terminal amide instead of a carboxyl group as in glutamate. These two are called the amide derivatives of their parent amino acids.

Now you've come to the end of the second part of the tutorial. You may have taken notes, and should be able to draw reasonably good diagrams (2D) of the following amino acids:
Alanine, Valine, Phenylalanine, Aspartic Acid, Lysine, Histidine, Serine, Glycine and Cysteine.

You should know general properties of these amino acids as they are classified above. When you have done the other parts of the tutorial you should have some idea about the different ways these amino acids can contribute to the structure of a protein. It will help if you know the three letter code for these amino acids.

When you feel ready, take the next part of the tutorial. Press NEXT in the small frame at lower left.