advances-in-protein-chemistry

Tyrosine Nitrated Proteins:
Biochemistry and
Pathophysiology
Abstract
Haseeb Ahsan*
Department of Biochemistry, Faculty of Dentistry, Jamia Millia
Islamia (A Central University), Okhla, New Delhi – 110025, India
*Corresponding author: Dr. Haseeb Ahsan, Department of
Biochemistry, Faculty of Dentistry, Jamia Millia Islamia (A Central
University), Okhla, New Delhi – 110025, India, E-mail: drhahsan@
gmail.com
The free radical-mediated damage to proteins results in the modification of amino acid residues, cross-linking of side chains and
fragmentation. L-tyrosine and protein bound tyrosine are prone to attack by various mediators and reactive nitrogen intermediates
to form 3-nitrotyrosine (3-NT). 3-NT formation is also catalyzed by a class of peroxidases utilizing nitrite and hydrogen peroxide as
substrates. Evidence supports the formation of 3-NT in vivo in diverse pathologic conditions and 3-NT is thought to be a relatively
specific marker of oxidative damage. The formation of nitrotyrosine represents a specific peroxynitrite-mediated protein modification;
thus, detection of nitrotyrosine in proteins is considered as a biomarker for endogenous peroxynitrite activity. Formation of tyrosine
nitrated proteins is considered to be a post-translational modification with important pathophysiological consequences and is one of the
markers of nitrosative stress that have been reported in neurodegeneration, inflammatory and other pathological conditions.
Introduction
Most proteins contain tyrosine residues with a natural abundance of about 3% [1]. Tyrosine (one letter abbreviation, Y; three letter
abbreviation, Tyr; also known as 4-hydroxyphenylalanine) is a non-essential amino acid and a member of the aromatic amino acid
group. Tyrosine is mildly hydrophilic, a characteristic feature that is explained by the rather hydrophobic aromatic benzene ring carrying
a hydroxyl group. As a consequence, tyrosine is often surface-exposed in proteins (only 15% of tyrosine residues are buried inside a
protein) and therefore should be available for modification such as nitration by various factors [2-4].
Tyrosine can be modified by the addition of a nitro group (-NO 2
) in vivo with several agents resulting in the formation of 3-nitrotyrosine
(3-NT) or tyrosine nitrated proteins (Figure 1). 3-NT [(2-Amino-3-(4-hydroxy-3-nitrophenyl) propanoic acid)] is a post-translational
modification in proteins occurring through the action of a nitrating agent resulting in the addition of a -NO 2
group (in ortho position
RNS
COO-
COO-
NO 2
metabolism
OH
Tyrosine
(Tyr)
Tyrosine decarboxylase
OH
Nitrotyrosine
(3-NT)
Tyramine oxidase
metabolism
COO-
+ +
NH 3 NH 3
COO-
RNS
OH
p-hydroxyphenylacetic acid
(PHPA)
OH
NO 2
3-nito-4-hydroxyphenylacetic acid
(NHPA)
Figure 1: Metabolism of tyrosine leading to the formation of products: p-hydroxyphenylacetic acid and 3-nitro-4-hydroxyphenylacetic acid (adapted
from Mani et al., 2003).
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