RT Book, Section
A1 Knerr, Ina
A1 Michael Gibson, K.
A1 Koch, Hans G.
A1 Häberle, Johannes
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181435510
T1 Glutaminase and Glutamine Synthetase: Biochemistry, Pharmacology and Mendelian Disorder
T2 The Online Metabolic and Molecular Bases of Inherited Disease
YR 2019
FD 2019
PB McGraw-Hill Education
PP New York, NY
SN 9780071459969
LK ommbid.mhmedical.com/content.aspx?aid=1181435510
RD 2024/10/13
AB The  amino  acid  L-glutamine  is  an  important  substrate  in  intermediary  metabolism  as  carrier  of  nitrogen  and  carbon  moieties.  Its  homeostasis  is  controlled  primarily  by  two  enzymes,  glutaminase  (glutamine  amidohydrolase)  and  glutamine  synthetase  (glutamate-ammonia  ligase).  This  chapter  provides  an  overview  of  the  molecular  and  protein  heterogeneity  of  these  two  enzymes  and  their  physiological  roles.  Murine  glutaminase  deficiency  and  glutamine  synthetase  deficiency,  both  in  Drosophila  and  in  two  patients,  also  are  summarized.  In  humans,  glutamine  synthetase  deficiency  (MIM  138290,  610015)  is  associated  with  severe  brain  malformations,  including  underdeveloped  gyri  and  intracranial  cysts,  as  well  as  with  respiratory  failure  and  early  death.  Both  patients  were  of  Turkish  descent  and  manifested  a  substitution  of  cysteine  for  arginine  in  exon  6  of  the  glutamine  synthetase  gene  (locus  1q31).  In  addition,  potential  pathomechanisms  of  secondary  glutamine  synthetase  deficiencies  (e.g.,  ammonia-induced  neurotoxicity  and  hepatic  encephalopathy)  also  are  discussed.