TY  - JOUR
AU  - Frieg, Benedikt
AU  - Görg, Boris
AU  - Gohlke, Holger
AU  - Häussinger, Dieter
TI  - Glutamine synthetase as a central element in hepatic glutamine and ammonia metabolism: novel aspects
JO  - Biological chemistry
VL  - 402
IS  - 9
SN  - 1437-4315
CY  - Berlin [u.a.]
PB  - de Gruyter
M1  - FZJ-2021-02624
SP  - 1063-1072
PY  - 2021
AB  - Glutamine synthetase (GS) in the liver is expressed in a small perivenous, highly specializedhepatocyte population and is essential for the maintenance of low, non‐toxic ammonia levelsin the organism. However, GS activity can be impaired by tyrosine nitration of the enzyme inresponse to oxidative/nitrosative stress in a pH‐sensitive way. The underlying molecularmechanism as investigated by combined molecular simulations and in vitro experimentsindicates that tyrosine nitration can lead to a fully reversible and pH‐sensitive regulation ofprotein function. This approach was also used to understand the functional consequences ofseveral recently described point mutations of human GS with clinical relevance and to suggestan approach to restore impaired GS activity.
LB  - PUB:(DE-HGF)16
C6  - pmid:33962502
UR  - <Go to ISI:>//WOS:000685568800006
DO  - DOI:10.1515/hsz-2021-0166
UR  - https://juser.fz-juelich.de/record/893207
ER  -