Arginine also plays an important role in nitrogen metabolism. In the urea cycle, the enzyme arginase cleaves (hydrolyzes) the guanidinium group to yield urea and the L-amino acid ornithine. Ornithine is lysine with one fewer methylene groups in the side chain. L-ornithine is not normally found in proteins.

There are 6 codons in the genetic code for arginine, yet, although this large a number of codons is normally associated with a high frequency of the particular amino acid in proteins, arginine is one of the least frequent amino acids. The discrepancy between the frequency of the amino acid in proteins and the number of codons is greater for arginine than for any other amino acid.

Asparagine has a high propensity to hydrogen bond, since the amide group can accept two and donate two hydrogen bonds. It is found on the surface as well as buried within proteins.

Asparagine is a common site for attachment of carbohydrates in glycoproteins.

Acidic

(Acidic R-group and their amides)

Polar (charged)

Proteins in the serum are critical to maintaining the pH balance in the body; it is largely the charged amino acids that are involved in the buffering properties of proteins. Aspartic acid is alanine with one of the β hydrogens replaced by a carboxylic acid group. The pKa of the β carboxyl group of aspartic acid in a polypeptide is about 4.0

Note that aspartic acid has an α-keto homolog, oxaloacetate, just as pyruvate is the α-keto homolog of alanine. Aspartic acid and oxaloacetate are interconvertable by a simple transamination reaction, just as alanine and pyruvate are interconvertible.

Oxaloacetate is one of the intermediates of the Krebs cycle.

(Sulfur containing group)
 

Consider, for example, the differences between H₂O and H₂S. The hydrogen bonding propensity of water is well known and is responsible for many of its remarkable features. Under similar conditions of temperature and pressure, however, H₂S is a gas as a consequence of its weak H-bonding propensity. Furthermore, the proton of the thiol of cysteine is much more acid than the hydroxylic proton of serine, making the nucleophilic thiol(ate) much more reactive than the hydroxyl of serine.

Cysteine also plays a key role in stabilizing extracellular proteins. Cysteine can react with itself to form an oxidized dimer by formation of a disulfide bond. The environment within a cell is too strongly reducing for disulfides to form, but in the extracellular environment, disulfides can form and play a key role in stabilizing many such proteins, such as the digestive enzymes of the small intestine.

Cysteine and methionine are the only sulfur-containing amino acids.

Acidic

(AcidicR-group and  their  amides)

Glutamic acid has one additional methylene group in its side chain than does aspartic acid. The side chain carboxyl of aspartic acid is referred to as the β carboxyl group, while that of glutamic acid is referred to as the γ carboxyl group.

The pK_a of the γ carboxyl group for glutamic acid in a polypeptide is about 4.3, significantly higher than that of aspartic acid. This is due to the inductive effect of the additional methylene group. In some proteins, due to a vitamin K dependent carboxylase, some glutamic acids will be dicarboxylic acids, referred to as γ carboxyglutamic acid, that form tight binding sites for calcium ion.

The additional single methylene group in the side chain relative to asparagine allows glutamine in the free form or as the N-terminus of proteins to spontaneously cyclize and deamidate yielding the six-membered ring structure pyrrolidone carboxylic acid, which is found at the N-terminus of many immunoglobulin polypeptides. This causes obvious difficulties with amino acid sequence determination.

The isoelectric point or isoelectric pH of glycine will be centered between the pK_as of the two ionizable groups, the amino group and the carboxylic acid group.

In estimating the pK_a of a functional group, it is important to consider the molecule as a whole. For example, glycine is a derivative of acetic acid, and the pK_a of acetic acid is well known. Alternatively, glycine could be considered a derivative of aminoethane.

The imidazole makes it a common participant in enzyme catalyzed reactions. The unprotonated imidazole is nucleophilic and can serve as a general base, while the protonated form can serve as a general acid. The residue can also serve a role in stabilizing the folded structures of proteins.

The side chains of these amino acids are not reactive and therefore not involved in any covalent chemistry in enzyme active centers.

However, these residues are critically important for ligand binding to proteins, and play central roles in protein stability. Note also that the β carbon of isoleucine is optically active, just as the β carbon of threonine. These two amino acids, isoleucine and threonine, have in common the fact that they have two chiral centers.

Like valine, leucine is hydrophobic and generally buried in folded proteins.

Lysine is basically alanine with a propylamine substituent on theβcarbon. The ε-amino group has a significantly higher pK_a (about 10.5 in polypeptides) than does the α-amino group.

The amino group is highly reactive and often participates in a reactions at the active centers of enzymes. Proteins only have one α amino group, but numerous ε amino groups. However, the higher pK_a renders the lysyl side chains effectively less nucleophilic. Specific environmental effects in enzyme active centers can lower the pKa of the lysyl side chain such that it becomes reactive.

Note that the side chain has three methylene groups, so that even though the terminal amino group will be charged under physiological conditions, the side chain does have significant hydrophobic character. Lysines are often found buried with only theεamino group exposed to solvent.

(Sulfur containing group)
 

The chemical linkage of the sulfur in methionine is a thiol ether. Compare this terminology with that of the oxygen containing ethers. The sulfur of methionine, as with that of cysteine, is prone to oxidation. The first step, yielding methionine sulfoxide, can be reversed by standard thiol containing reducing agents. The second step yields methionine sulfone, and is effectively irreversible. It is thought that oxidation of the sulfur in a specific methionine of the elastase inhibitor in human lung tissue by agents in cigarette smoke is one of the causes of smoking-induced emphysema.

Methionine as the free amino acid plays several important roles in metabolism. It can react to form S-Adenosyl-L-Methionine (SAM) which servers at a methyl donor in reactions.

Methionine and cysteine are the only sulfur-containing amino acids.
 

Cyclic

   Biosynthesis of Proline

Nonpolar

Proline is formally NOT an amino acid, but an imino acid. Nonetheless, it is called an amino acid. The primary amine on the α carbon of glutamate semialdehyde forms a Schiff base with the aldehyde which is then reduced, yielding proline.

When proline is in a peptide bond, it does not have a hydrogen on the α amino group, so it cannot donate a hydrogen bond to stabilize an α helix or a β sheet. It is often said, inaccurately, that proline cannot exist in an α helix. When proline is found in an α helix, the helix will have a slight bend due to the lack of the hydrogen bond.

Proline is often found at the end of α helix or in turns or loops. Unlike other amino acids which exist almost exclusively in the trans- form in polypeptides, proline can exist in the cis-configuration in peptides. The cis and trans forms are nearly isoenergetic. The cis/trans isomerization can play an important role in the folding of proteins and will be discussed more in that context.

Proline is the only cyclic amino acid.

(Hydroxyl group)

Serine is one of two hydroxyl amino acids. Both are commonly considered to by hydrophilic due to the hydrogen bonding capacity of the hydroxyl group.
 

(Hydroxyl group)
 

Threonine is an other hydroxyl-containing amino acid. It differs from serine by having a methyl substituent in place of one of the hydrogens on the β carbon and it differs from valine by replacement of a methyl substituent with a hydroxyl group.

Note that both the α and β carbons of threonine are optically active.

Tyrosine absorbs ultraviolet radiation and contributes to the absorbance spectra of proteins. The absorbance spectrum of tyrosine will be shown later; the extinction of tyrosine is only about 1/5 that of tryptophan at 280 nm, which is the primary contributor to the UV absorbance of proteins depending upon the number of residues of each in the protein.

Valine differs from threonine by replacement of the hydroxyl group with a methyl substituent. Valine is often referred to as one of the amino acids with hydrocarbon side chains, or as a branched chain amino acid.

Note that valine and threonine are of roughly the same shape and volume. It is difficult even in a high resolution structure of a protein to distinguish valine from threonine.