Determining the molecular consequences of clinically relevant glutamine synthetase mutations

Glutamine synthetase (GS) catalyzes the ligation of ammonia and glutamate to glutamine under the use of ATP and is, thus, essential for nitrogen metabolism [1,2]. Loss of hepatic GS activity has been linked to serious clinical conditions [3]. In particular, two mutations of human GS (R324C and R341C) were connected to congenital glutamine deficiency with severe brain malformations resulting in neonatal death [4]. In a single case known to date, to the best of our knowledge, another GS mutation (R324S) was identified in a neurologically compromised patient [5]. However, the underlying molecular mechanisms of GS d…