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The glycerophospho metabolome and its influence on amino acid homeostasis revealed by brain metabolomics of GDE1(-/-) mice

Citation:

Kopp F, Komatsu T, Nomura DK, Trauger SA, Thomas JR, Siuzdak G, Simon GM, Cravatt BF. The glycerophospho metabolome and its influence on amino acid homeostasis revealed by brain metabolomics of GDE1(-/-) mice. Chem BiolChem BiolChem Biol. 2010;17 :831-40.

Date Published:

Aug 27

Abstract:

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/DA/NIDA NIH HHS/R01 CA132630/CA/NCI NIH HHS/R01 CA132630-04/CA/NCI NIH HHS/R01CA132630/CA/NCI NIH HHS/Chem Biol. 2010 Aug 27;17(8):831-40. doi: 10.1016/j.chembiol.2010.06.009.