section
2.2
Classification
25
groups and can be inactivated by irreversible derivatiza-
tion of these groups. The -OH group of serine has a weakly
acidic pK' of 13.6.
Threonine
This essential amino acid has a second asymmetrical
carbon atom in the side chain and therefore can have four
isomers, only one of
COO"
I
+ H3N— C— H
I
H— C— OH
I
CH3
Threonine
which, L-threonine, occurs in proteins. The hydroxyl
group, as in the case of serine, participates in reactions
with phosphoric acid and with sugar residues.
Cysteine
The weakly acidic (pK' = 8.33) sulfhydryl group (-SH)
of cysteine is essentially undissociated at physiological
pH. Free -SH groups are essential for the function of many
enzymes and structural proteins. Heavy metal ions, e.g.,
Pb2+ and Hg2+, inactivate these proteins by combining
with their -SH groups. Two cysteinyl -SH groups can be
oxidized to form
cystine.
A covalent disulfide bond of cys-
tine can join two parts of a single polypeptide chain or two
different polypeptide chains through cross-linking of cys-
teine residues. These -S -S - bonds are essential both for
the folding of polypeptide chains and for the association
of polypeptides in proteins that have more than one chain,
e.g., insulin and immunoglobulins.
COO"
+ H3N— C— H
I
CH2
I
SH
Cysteine
Tyrosine
The phenolic hydroxyl group of this aromatic amino
acid has a weakly acidic pK' of about 10 and therefore
is un-ionized at physiological pH. In some enzymes, the
hydrogen of the phenolic hydroxyl group can participate
in hydrogen bond formation with oxygen and nitrogen
atoms. The phenolic hydroxyl group of tyrosine residues
in protein can be sulfated (e.g., in gastrin and chole-
cystokinin; see Chapter 12) or phosphorylated by a re-
action catalyzed by the tyrosine-specific protein kinase
that is a product of some oncogenes (Chapter 26). Tyro-
sine kinase activity also resides in a family of cell sur-
face receptors that includes receptors for such anabolic
polypeptides as insulin, epidermal growth factor, platelet-
derived growth factor, and insulin-like growth factor type
1. All of these receptors have a common motif of an ex-
ternal ligand binding domain, a transmembrane segment,
and a cytoplasmic tyrosine kinase domain (Chapter 22).
Tyrosine accumulates in tissues and blood in
tyrosinosis
and
tyrosinemia,
which are due to inherited defects in
catabolism of this amino acid. Tyrosine is the biosynthetic
precursor of thyroxine, catecholamines, and melanin.
Tyrosine and its biosynthetic precursor, phenylalanine,
both absorb UV light (Figure 2-4).
ccxr
I
+ H3N— C— H
CH2
OH
Tyrosine
Asparagine
The R-group of this amide derivative of aspartic acid has
no acidic or basic properties but is polar and participates in
hydrogen bond formation. It is hydrolyzed to aspartic acid
and ammonia by the enzyme asparaginase. In glycopro-
teins, the carbohydrate side chain is often linked through
the amide group of asparagine.
coo"
I
+ H3N— C— H
I
CH2
I
0
<^ ^NHz
Asparagine
COO"
COO"
+
I
I
+ H3N— C— H
+ H3N
— C— H
I
I
CH2
-------
s—S
------------CH2
Cystine
