Alanine is a hydrophobic molecule. It is ambivalent, meaning that it can be inside or outside of the protein molecule. The α carbon of alanine is optically active; in proteins, only the L-isomer is found.

Note that alanine is the α-amino acid analog of the α-keto acid pyruvate, an intermediate in sugar metabolism. Alanine and pyruvate are interchangeable by a transamination reaction.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Arginine, an essential amino acid, has a positively charged guanidino group. Arginine is well designed to bind the phosphate anion, and is often found in the active centers of proteins that bind phosphorylated substrates. As a cation, arginine, as well as lysine, plays a role in maintaining the overall charge balance of a protein.

Arginine also plays an important role in nitrogen metabolism.Chemical structure of Urea H2N -C(O)-NH2 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.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Asparagine is the amide of aspartic acid. The amide group does not carry a formal charge under any biologically relevant pH conditions. The amide is rather easily hydrolyzed, converting asparagine to aspartic acid. This process is thought to be one of the factors related to the molecular basis of aging.

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 the attachment of carbohydrates in glycoproteins.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Aspartic acid is one of two acidic amino acids. Aspartic acid and glutamic acid play important roles as general acids in enzyme active centers, as well as in maintaining the solubility and ionic character of proteins.

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.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Cysteine is one of two sulfur-containing amino acids; the other is methionine. Cysteine differs from serine in a single atom-- the sulfur of the thiol replaces the oxygen of the alcohol. The amino acids are, however, much more different in their physical and chemical properties than their similarity might suggest.

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 the 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.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

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 pKa 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.

• Glutamic acid is interconvertible by transamination withα-ketoglutarate

Glutamic acid and α-ketoglutarate, an intermediate in the Krebs cycle, are interconvertible by transamination. Glutamic acid can therefore enter the Krebs cycle for energy metabolism, and be converted by the enzyme glutamine synthetase into glutamine, which is one of the key players in nitrogen metabolism.

• Biosynthesis of Proline

Note also that glutamic acid is easily converted into proline. First, the γ carboxyl group is reduced to the aldehyde, yielding glutamate semialdehyde. The aldehyde then reacts with the α-amino group, eliminating water as it forms the Schiff base. In a second reduction step, the Schiff base is reduced, yielding proline.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Glutamine is the amide of glutamic acid, and is uncharged under all biological conditions.

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.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Glycine is the smallest of the amino acids. It is ambivalent, meaning that it can be inside or outside of the protein molecule. In aqueous solution at or near neutral pH, glycine will exist predominantly as the zwitterion

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

In estimating the pKa 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 pKa of acetic acid is well known. Alternatively, glycine could be considered a derivative of aminoethane

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Histidine, an essential amino acid, has as a positively charged imidazole functional group.

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.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Isoleucine, an essential amino acid, is one of the three amino acids having branched hydrocarbon side chains. It is usually interchangeable with leucine and occasionally with valine in 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.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Leucine, an essential amino acid, is one of the three amino acid with a branched hydrocarbon side chain. It has one additional methylene group in its side chain compared with valine.

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

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Lysine. an essential amino acid, has a positively charged ε-amino group (a primary amine).

Lysine is basically alanine with a propylamine substituent on theβcarbon. The ε-amino group has a significantly higher pKa (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 pKa 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.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Methionine, an essential amino acid, is one of the two sulfur-containing amino acids. The side chain is quite hydrophobic and methionine is usually found buried within proteins. Unlike cysteine, the sulfur of methionine is not highly nucleophilic, although it will react with some electrophilic centers. It is generally not a participant in the covalent chemistry that occurs in the active centers of enzymes.

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.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

As the name suggests, phenylalanine, an essential amino acid, is a derivative of alanine with a phenyl substituent on the β carbon. Phenylalanine is quite hydrophobic and even the free amino acid is not very soluble in water.

It is an interesting point of history that Marshall Nirenberg and Phil Leder in their earliest experiments were studying the translation of the synthetic message polyU, which encodes polyphenylalanine. It was a happy coincidence that the product was insoluble. At the time, they did not know that UUU encodes Phe, but soon after the precipitate formed in their translation mix, they did, and they were on the way to unraveling the genetic code, and the Nobel prize.

Due to its hydrophobicity, phenylalanine is nearly always found buried within a protein. The π electrons of the phenyl ring can stack with other aromatic systems and often do within folded proteins, adding to the stability of the structure.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Proline shares many properties with the aliphatic group.

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.

• Biosynthesis of Proline

Glutamic acid is easily converted into proline. First, the γcarboxyl group is reduced to the aldehyde, yielding glutamate semialdehyde. The aldehyde then reacts with the α-amino group, eliminating water as it forms the Schiff base. In a second reduction step, the Schiff base is reduced, yielding proline.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Serine differs from alanine in that one of the methylenic hydrogens is replaced by a 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.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Threonine, an essential amino acid, is a hydrophilic molecule.

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.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Tryptophan, an essential amino acid, is the largest of the amino acids. It is also a derivative of alanine, having an indole substituent on the β carbon. The indole functional group absorbs strongly in the near ultraviolet part of the spectrum. The indole nitrogen can hydrogen bond donate, and as a result, tryptophan, or at least the nitrogen, is often in contact with solvent in folded proteins.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Tyrosine, an essential amino acid, is also an aromatic amino acid and is derived from phenylalanine by hydroxylation in the para position. While tyrosine is hydrophobic, it is significantly more soluble that is phenylalanine. The phenolic hydroxyl of tyrosine is significantly more acidic than are the aliphatic hydroxyls of either serine or threonine, having a pKa of about 9.8 in polypeptides. As with all ionizable groups, the precise pKa will depend to a major degree upon the environment within the protein. Tyrosines that are on the surface of a protein will generally have a lower pKa than those that are buried within a protein; ionization yielding the phenolate anion would be exceedingly unstable in the hydrophobic interior of a protein.

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.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html

Valine, an essential amino acid, is hydrophobic, and as expected, is usually found in the interior of proteins.

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.

Source: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Dayhoff.html