title: The glycerophospho metabolome and its influence on amino acid homeostasis revealed by brain metabolomics of GDE1(-/-) mice.
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.
authors.affiliation: Department of Chemical Physiology and The Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Kopp
authors.forename: Toru
authors.initials: T
authors.lastname: Komatsu
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Nomura
authors.forename: Sunia A
authors.initials: SA
authors.lastname: Trauger
authors.forename: Jason R
authors.initials: JR
authors.lastname: Thomas
authors.forename: Gary
authors.initials: G
authors.lastname: Siuzdak
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Simon
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Cravatt
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D006706:Homeostasis; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D010727:Phosphoric Diester Hydrolases / Q000172:deficiency* / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000596:Amino Acids; D007295:Inositol Phosphates; D014867:Water; C014575:glycerylphosphoinositol; D012694:Serine; D010727:Phosphoric Diester Hydrolases; C038133:glycerophosphodiester phosphodiesterase
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