Premium
Reversible inhibition of mammalian glutamine synthetase by tyrosine nitration
Author(s) -
Görg Boris,
Qvartskhava Natalia,
Voss Peter,
Grune Tilman,
Häussinger Dieter,
Schliess Freimut
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.11.081
Subject(s) - peroxynitrite , nitration , tyrosine , chemistry , biochemistry , nitrosylation , glutamine synthetase , oxidative stress , nitrotyrosine , enzyme , nitric oxide , glutamine , nitric oxide synthase , amino acid , organic chemistry , superoxide
The effect of tyrosine nitration on mammalian GS activity and stability was studied in vitro. Peroxynitrite at a concentration of 5 μmol/l produced tyrosine nitration and inactivation of GS, whereas 50 μmol/l peroxynitrite additionally increased S ‐nitrosylation and carbonylation and degradation of GS by the 20S proteasome. (−)Epicatechin completely prevented both, tyrosine nitration and inactivation of GS by peroxynitrite (5 μmol/l). Further, a putative “denitrase” activity restored the activity of peroxynitrite (5 μmol/l)‐treated GS. The data point to a potential regulation of GS activity by a reversible tyrosine nitration. High levels of oxidative stress may irreversibly damage and predispose the enzyme to proteasomal degradation.