Basic Structure of
Amino Acids

Chemical Families
   
Acidic & Amides
   
Aliphatic
   
Aromatic
   
Basic
   
Cyclic

   Hydroxyl
   Sulfur-Containing

Structural Families
   
Gly to Leu
   Asp to Gln
   Ala to Trp

 Author of 1 letter codes
 
Dr. M.O. Dayhoff

The Chemistry of Amino Acids

From: The Chemistry of Amino Acids

Introduction
Essential amino acids

Amino acids play central roles both as building blocks of proteins and as intermediates in metabolism. The 20 amino acids that are found within proteins convey a vast array of chemical versatility. The precise amino acid content, and the sequence of those amino acids, of a specific protein, is determined by the sequence of the bases in the gene that encodes that protein. The chemical properties of the amino acids of proteins determine the biological activity of the protein. Proteins not only catalyze all (or most) of the reactions in living cells, they control virtually all cellular process. In addition, proteins contain within their amino acid sequences the necessary information to determine how that protein will fold into a three dimensional structure, and the stability of the resulting structure. The field of protein folding and stability has been a critically important area of research for years, and remains today one of the great unsolved mysteries. It is, however, being actively investigated, and progress is being made every day.

As we learn about amino acids, it is important to keep in mind that one of the more important reasons to understand amino acid structure and properties is to be able to understand protein structure and properties. We will see that the vastly complex characteristics of even a small, relatively simple, protein are a composite of the properties of the amino acids which comprise the protein.

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Essential amino acids

Humans can produce 10 of the 20 amino acids. The others must be supplied in the food. Failure to obtain enough of even 1 of the 10 essential amino acids, those that we cannot make, results in degradation of the body's proteins—muscle and so forth—to obtain the one amino acid that is needed. Unlike fat and starch, the human body does not store excess amino acids for later use—the amino acids must be in the food every day.

The 10 amino acids that we can produce are alanine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine and tyrosine. Tyrosine is produced from phenylalanine, so if the diet is deficient in phenylalanine, tyrosine will be required as well. The essential amino acids are arginine (required for the young, but not for adults), histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. These amino acids are required in the diet. Plants, of course, must be able to make all the amino acids. Humans, on the other hand, do not have all the the enzymes required for the biosynthesis of all of the amino acids.

 

 

 


Amino Acids

   Alanine
   Arginine
   Asparagine
   Aspartic acid
   Cysteine
   Glutamic acid
   Glutamine
   Glycine
   Histidine
   Isoleucine
   Leucine
   Lysine
   Methionine
   Phenylalanine
   Proline
   Serine
   Threonine
   Tryptophan
   Tyrosine
   Valine

Atoms in Amino Acids
Legend describing the atoms of hydrogen, carbon, nitrogen, oxygen and sulfur found in amino acids


Basic Structure of an Amino Acid


Basic StructureBasic structue of an amino acids: alpha carbon, alpha hydrogen, alpha carboxyl group, alpha amino group and R-group

All amino acids found in proteins have this basic structure, differing only in the structure of the R-group or the side chain..

The simplest, and smallest, amino acid found in proteins is glycine for which the R-group is a hydrogen (H).


L-isomer
In proteins, only the L-isomer is found normally.

As you travel onward (from the carbonyl carbon to the amino group), the R group of L-amino acids will be on the left as shown in the molecular graphic on the right

basic structure of amino acid demonstrating that the R group of L-amino acids is on the left

Acidic Amino Acids and their Amides

Acidic amino acids are polar and negatively charged at physiological pH. Both acidic amino acids have a second carboxyl group.

Amides are polar and uncharged, and not ionizable. All are very hydrophilic.

Acidic amino acid

Amide   Acidic amino acid Amide
Molecular structure of aspartic acid  HOOC-CH3-CH(NH3)-COO
Molecualar structure of Asparagine  H2N-CO-CH2-CH(NH3)-COO   Molecular structure of glutamic acid  HOOC-(CH2)2-CH(NH3)-COO
molecular structure of glutamine H2N-CO-(CH2)2-CH(NH3)-COO
Chemical structure for aspartic acid
Chemical structure for asparagine
 
Chemical structure of glutamic acid
Chemical structure for glutamine

Aliphatic Amino Acids

Aliphatic R groups are nonpolar and hydrophobic. Hydrophobicity increases with increasing number of C atoms in the hydrocarbon chain. Although these amino acids prefer to remain inside protein molecules, alanine and glycine are ambivalent, meaning that they can be inside or outside the protein molecule. Glycine has such a small side chain that it does not have much effect on the hydrophobic interactions.

The structures below are shown in the ionization state that predominates at pH 7.

Molecular Structure of Glycine NH2-CH2-COOH Molecualar Structure of Alanine CH3-CH(NH3)-COO- Molecular structure of valine (CH3)2-CH-CH(NH3)-COO Molecular Structure for Leucine (CH3)2-CH-CH2-CH(NH3)-COOMolecular Structure of Isoleucine CH3-CH2-CH(CH3)-CH(NH3)-COO
Less hydrophobic More hydrophobic
Chemical structure for glycine Chemical structure for alanine Chemcial structure for valine chemical structure of valine Chemical structure for isoleucine

Aromatic Amino Acids

Aromatic amino acids are relatively nonpolar. To different degrees, all aromatic amino acids absorb ultraviolet light. Tyrosine and tryptophan absorb more than do phenylalanine; tryptophan is responsible for most of the absorbance of ultraviolet light (ca. 280 nm) by proteins. Tyrosine is the only one of the aromatic amino acids with an ionizable side chain. Tyrosine is one of three hydroxyl containing amino acids.

molecular structure of tyrosine HO-p-Ph-CH2-CH(NH3)-COO molecular structure of tryptophanPh-NH-CH=C-CH2-CH(NH3)-COO Molecular structure of phenylalanine
Least hydrophobic Very hydrophobic

Chemical structure for tyrosine
Chemical structure for tryptophan
chemical structure for phenylalanine

Basic Amino Acids

Basic amino acids are polar and positively charged at pH values below their pKa's, and are very hydrophilic. Even though the basic amino acids are almost always in contact with the solvent, the side chain of lysine has a marked hydrocarbon character, so it is often found NEAR the surface, with the amino group of the side chain in contact with solvent. Note that in the drawing, histidine is shown in the protonated form, while at pH 7.0, the imidazole would exist predominantly in the neutral form.

Molecular structure for histidine NH-CH=N-CH=C-CH2-CH(NH3)-COO Molecular structure for lysine H2N-(CH2)4-CH(NH3)-COO Molecular structure of arginine HN=C(NH2)-NH-(CH2)3-CH(NH3)-COO
Chemical structure of histidine Chemical structure for lysine Chemical structure for arginine

Cyclic Amino Acid

Proline is the only cyclic amino acid. It is nonpolar and shares many properties with the aliphatic group.

Proline is one of the ambivalent amino acids, meaning that it can be inside or outside of a protein molecule. Due to its unique structure, proline occurs in proteins frequently in turns or bends, which are often on the surface. The structure shown is of the amino acid in the ionization state that predominates at pH 7.0.

Molecular Structure of Proline NH2-(CH2)3-CH-COO
Chemical structure for proline

Hydroxyl Amino Acids

Hydroxyl amino acids are polar, uncharged at physiological pH, and hydrophilic. The phenolic hydroxyl ionizes with a pKa of 10 to yield the phenolate anion. The hydroxyl groups of serine and threonine are so high that they are generally regarded as nonionizing.

Molecular Structure for Serine HO-CH2-CH(NH3)-COO molecular structure of threonine CH3-CH(OH)-CH(NH3)-COO Molecular Structure of Tyrosine HO-p-Ph-CH2-CH(NH3)-COO
Chemical structure for serine   Chemical structure for threonine    Chemical structure of tyrosine

Sulfur-Containing Amino Acids

The sulfur-containing amino acids (cysteine and methionine) are generally considered to be nonpolar and hydrophobic. In fact, methionine is one of the most hydrophobic amino acids and is almost always found on the interior of proteins. Cysteine on the other hand does ionize to yield the thiolate anion. Even so, it is uncommon to find cysteine on the surface of a protein. There are several reasons. First, sulfur has a low propensity to hydrogen bond, unlike oxygen. A consequence of this fact is that H2S is a gas under conditions that H2O is a liquid. Second, the thiol group of cysteine can react with other thiol groups in an oxidation reaction that yields a disulfide bond. Perhaps as a consequence, cysteine residues are most frequently buried inside proteins.

molecular structure of cysteine HS-CH2-CH(NH3)-COOmolecular structure of methionine CH3-S-(CH2)2-CH(NH3)-COO
   
Chemical structure for cysteine    Chemical structure for methionine

Dr. Margaret Oakley Dayhoff

Note about Dr. Dayhoff
Biophysical Society

The origin of the single-letter code for the amino acids

The origin of the single-letter code for the amino acids is of historical interest, and in fact, this story may help the student to learn the code.  The reason for the code is simple enough–in the very early days of bioinformatics, the very fastest computers were in fact, rather clunky.  Dr. Margaret Oakley Dayhoff, arguably the founder of the field of bioinformatics, shortened the code from the three letter designations to the single letter code in an effort to reduce the size of the data files needed to describe the sequence of amino acids in a protein.  The listing of amino acids, the three letter and single letter code, and the explanation for the choice of the single letter is given below.  Note that there are 20 amino acids commonly found in proteins, and 26 letters in the alphabet.  As a result, most of the letters are used.

To develop a single-letter code for the amino acids, Dr. Dayhoff attempted to make the code as easy to remember as possible.  Of course, if the name of each amino acid began with a different letter, the code would be simple indeed.  For 6 of the amino acids, the first letter of the name is unique, making the code simple.  These are:

Amino Acid
3 letter code
Single letter code
Explanation

Cysteine
Histidine
Isoleucine
Methionine
Serine
Valine

Cys
His
Ile
Met
Ser
Val
C
H
I
M
S
V
First letter of the name
First letter of the name
First letter of the name
First letter of the name
First letter of the name
First letter of the name

For the other amino acids, the first letter of the name is not unique to a single amino acid, so Dr. Dayhoff assigned the letters A, G, L, P and T to the amino acids Alanine, Glycine, Leucine, Proline and Threonine, respectively, which occur more frequently in proteins than do the other amino acids having the same first letters.

Amino Acid
3 letter code
Single letter code
Explanation
Alanine
Glycine
Leucine
Proline
Threonine
Ala
Gly
Leu
Pro
Thr
A
G
L
P
T
First letter of the name
First letter of the name
First letter of the name
First letter of the name
First letter of the name

Some of the other amino acids are phonetically suggestive. 

Amino Acid
3 letter code
Single letter code
Explanation
Arginine
Phenylalanine
Tyrosine
Tryptophan
Arg
Phe
Tyr
Trp
R
F
Y
W

aRginine
Fenylalanine
tYrosine
tWiptophan (or, contains Double ring)

For the remaining 5 amino acids, Dr. Dayhoff was reaching somewhat to find an easy-to-remember connection between the single letter and the amino acid.  She assigned aspartic acid, asparagine, glutamic acid and glutamine the letters D, N, E and Q, respectively, noting that D and N are nearer the beginning of the alphabet than E and Q, and that Asp is smaller than Glu, while Asn is smaller than Gln. 

Amino Acid
3 letter code
Single letter code
Explanation
Aspartic Acid
Asparagine
Glutamic Acid
Glutamine
Asp
Asn
Glu
Gln

D
N
E
Q


asparDic
Contains N (or asparagiN)
gluE (or glutamEke)
Q-tamine

By the time Dr. Dayhoff got to lysine, there were not too many letters left, so she used the letter K, explaining that K is at least near L in the alphabet.

Amino Acid
3 letter code
Single letter code
Explanation
Lysine
Lys
K

K is near L in the alphabet

Note about Dr. Margaret Oakley Dayhoff (1925-1983)

Professional Obituary

Dr. Margaret Oakley Dayhoff was a professor at Georgetown University Medical Center and a noted research biochemist at the National Biomedical Research Foundation where she pioneered the application of mathematics and computational methods to the field of biochemistry.  Dr. Dayhoff dedicated her career to applying the evolving computational technologies to support advances in biology and medicine, most notably the creation of protein and nucleic acid databases and tools to interrogate the databases.  Her PhD degree was from Columbia University in the Department of Chemistry, where she devised computational methods to calculate  molecular resonance energies of several organic compounds.  She did postdoctoral studies at the Rockefeller Institute (now Rockefeller University) and the University of Maryland, and joined the newly established National Biomedical Research Foundation in 1959.

Dr. Dayhoff's work with proteins began in 1961 when she developed tools to aid protein chemists in determination of amino acid sequences by automatically overlapping the sequences of peptides.  She went on to initiate the "Atlas of Protein Sequence and Structure", and to develop many of the tools used today in database design and utilization.  In 1980, Dr. Dayhoff developed an on-line database system that could be accessed by telephone line, the first sequence database available for interrogation by remote computers.  Dr. Margaret Oakley Dayhoff, the founder of the field of bioinformatics, died before the field was recognized as a distinct area for investigation.  She was, indeed, a pioneer.

Dr. Dayhoff was extremely active in the Biophysical Society, and served the society as both its secretary and president.  One of her interests was in enhancing the ability of women to successfully pursue careers in the sciences.  She was well aware of the many challenges facing women in science, and worked hard to encourage and mentor women in scientific careers.  It is therefore fitting that the Margaret Oakley Dayhoff award was established to encourage young women to enter careers in scientific research.  This award is aimed towards women of very high promise who have not yet reached a position of high recognition within the structure of academic society.  It is administered through the Biophysical Society , and candidates are judged on achievement and promise in fields within the purvue of the Biophysical Society .

 


Alanine A (Ala)

Chemical Properties:
    Aliphatic
(Aliphatic R-group)

Physical Properties:
    Nonpolar

 

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.

Molecualar Structure of Alanine CH3-CH(NH3)-COO-
Chemical structure of Alanine
Interchangeable with Pyruvate
Molecular Structure for Pyruvate CH3-C(O)-COO-
Chemical structure of Pyruvate

Arginine R (Arg)

Chemical Properties:
    Basic
(Basic R-group)
Physical Properties:
    Polar (positively charged)
  


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.

Molecular Structure of Arginine HN=C(NH2)-NH-(CH2)3-CH(NH3)-COO
Chemical structure of arginine

Asparagine N (Asn)

Chemical Properties:
    Neutral
(Amides of acidic amino acids R-group)

Physical Properties:
   Polar (uncharged)
   

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 attachment of carbohydrates in glycoproteins.

molecular structure of asparagine H2N-CO-CH2-CH(NH3)-COO
Chemical structure for asparagine


Aspartic Acid D (Asp)

Chemical Properties: Physical Properties:

  


Acidic

(Acidic R-group and their amides)


Polar (charged)

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.

molecular structure  HOOC-CH3-CH(NH3)-COO
Chemical structure for aspartic acid
Aspartic acid and oxaloacetate are interconvertable by a simple transamination reaction
Molecular Structure of oxaloacetate COO-­CH2­CO­COO-
Chemical structure of oxaloacetate

Cysteine C (Cys)

Chemical Properties:
    Sulfur-containing

(Sulfur containing group)

Physical Properties:
    Polar (uncharged)
 


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 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.

molecular structure for  HS-CH2-CH(NH3)-COO

Chemical structure for cysteine


Glutamic Acid E (Glu)

Chemical Properties:

Acidic

(Acidic R-group and their amides)

Physical Properties:

Polar (charged)

   Interconvertible with α-ketoglutarate
   Biosynthesis of Proline

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.

Molecular structure of glutamic acid  HOOC-(CH2)2-CH(NH3)-COO
Chemical structure for glutamic acid

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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.

Molecular Structure of alpha-ketoglutarate COO-­CH2­Ch2­CO­COO-
Chemical structure of alpha-ketoglutarate
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.
Glutamic acid to Glutamate Semialdehyde to pyrroline 5-carboxylate to Proline
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Glutamine Q (Gln)

Chemical Properties:
    Neutral
(Amides of acidic amino acids R-group)

Physical Properties:
   Polar (uncharged)


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.

Molecule Structure of Glutamine H2N-CO-(CH2)2-CH(NH3)-COO
      Chemical structure for glutamine

Glycine G (Gly)

Chemical Properties:
    Aliphatic
(Aliphatic R-group)

 

Physical Properties:     
Nonpolar
   

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.

Molecular Structure of Glycine NH2-CH2-COOH
Chemical structure for glycine

Histidine H (His)

Chemical Properties:
    Basic
(Basic group)
Physical Properties:
    Polar (positively charged)
   


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.

molecular structure for histidine NH-CH=N-CH=C-CH2-CH(NH3)-COO
Chemical structure of histidine

Isoleucine I (Ile)

Chemical Properties:
    Aliphatic
(Aliphatic R-group)
Physical Properties:
    Nonpolar 
  


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.

Molecular Structure of Isoleucine CH3-CH2-CH(CH3)-CH(NH3)-COO


Chemcial structure for Isoleucine


Leucine L (Leu)

Chemical Properties:
    Aliphatic
(Aliphatic R-group)
Physical Properties:
    Nonpolar


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.

Molecular Structure for Leucine (CH3)2-CH-CH2-CH(NH3)-COO
Chemical structure for leucine

Lysine K (Lys)

Chemical Properties:
    Basic
(Basic R-group)
Physical Properties:
    Polar (positively charged)


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.

Molecular structure of Lysine H2N-(CH2)4-CH(NH3)-COO
Chemcial structure for lysine

Methionine M (Met)

Chemical Properties:
    Sulfur-containing

(Sulfur containing group)

Physical Properties:
 Non polar (hydrophobic)
 


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.

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

Molecular structure of methionine CH3-S-(CH2)2-CH(NH3)-COO
Chemical structure for methionine


Phenylalanine F (Phe)

Chemical Properties:
    Aromatic
(Aromatic R-group)
Physical Properties:
    Nonpolar

  


 


 

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.

Molecular structure of phenylalaline
Chemical structure for phenylalanine

Proline P (Pro)

Chemical Properties: Physical Properties:

  


Cyclic
   Biosynthesis of Proline

Nonpolar

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.

Proline is the only cyclic amino acid.

Molecular Structure of proline, NH2-(CH2)3-CH-COO

Chemical structure of Proline
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.
Glutamic acid to Glutamate Semialdehyde to pyrroline 5-carboxylate to Proline
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Serine S (Ser)

Chemical Properties:
    Non-aromatic
hydroxyl

(Hydroxyl group)

Physical Properties:
    Polar (uncharged)


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.

Molecular Structure of Serine HO-CH2-CH(NH3)-COO
Chemical structure for serine

Threonine T (Thr)

Chemical Properties:
    Non-aromatic
hydroxyl

(Hydroxyl group)

Physical Properties:
    Polar (uncharged) 

 

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.

molecular structure for threonine CH3-CH(OH)-CH(NH3)-COO
Chemical structure for threonine
Differs from serine
Molecular structure of Serine HO-CH2-CH(NH3)-COO
Chemical structure of Serine
Differs from valine
Molecular Structure of Valine (CH3)2-CH-CH(NH3)-COO
Chemical structure of valine
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Tryptophan W (Trp)

Chemical Properties:
    Aromatic
(Aromatic R-group)
Physical Properties:
    Nonpolar

  


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.

molecular structure for tryptophan Ph-NH-CH=C-CH2-CH(NH3)-COO
Chemical structure for tryptophan

Tyrosine Y (Tyr)

Chemical Properties:
    Aromatic
(Aromatic group & Hydroxyl group)
Physical Properties:
    Nonpolar

  


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.

molecular structure for tyrosine
Chemical structure of tyrosine

Valine V (Val)

Chemical Properties:
    Aliphatic
(Aliphatic R-group)

Physical Properties:
   Nonpolar

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.   

Molecular Structure of Valine (CH3)2-CH-CH(NH3)-COO
    
Chemical structure for valine

Differs from threonine
Molecular structure of Threonine CH3-CH(OH)-CH(NH3)-COO
Chemical Structure of threonine
 
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