Citation:
Date Published:
Aug 27Abstract:
GDE1 is a mammalian glycerophosphodiesterase (GDE) implicated by in vitro studies in the regulation of glycerophophoinositol (GroPIns) and possibly other glycerophospho (GroP) metabolites. Here, we show using untargeted metabolomics that GroPIns is profoundly (>20-fold) elevated in brain tissue from GDE1(-/-) mice. Furthermore, two additional GroP metabolites not previously identified in eukaryotic cells, glycerophosphoserine (GroPSer) and glycerophosphoglycerate (GroPGate), were also highly elevated in GDE1(-/-) brains. Enzyme assays with synthetic GroP metabolites confirmed that GroPSer and GroPGate are direct substrates of GDE1. Interestingly, our metabolomic profiles also revealed that serine (both L-and D-) levels were significantly reduced in brains of GDE1(-/-) mice. These findings designate GroPSer as a previously unappreciated reservoir for free serine in the nervous system and suggest that GDE1, through recycling serine from GroPSer, may impact D-serine-dependent neural signaling processes in vivo.
Notes:
Kopp, FlorianKomatsu, ToruNomura, Daniel KTrauger, Sunia AThomas, Jason RSiuzdak, GarySimon, Gabriel MCravatt, Benjamin FK99 DA030908/DA/NIDA NIH HHS/P01 DA017259-08/DA/NIDA NIH HHS/R01 CA132630-04/CA/NCI NIH HHS/R01 CA132630-05/CA/NCI NIH HHS/R01CA132630/CA/NCI NIH HHS/Chem Biol. 2010 Aug 27;17(8):831-40.