Literature DB >> 20797612

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

Florian Kopp1, Toru Komatsu, Daniel K Nomura, Sunia A Trauger, Jason R Thomas, Gary Siuzdak, Gabriel M Simon, Benjamin F Cravatt.   

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. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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Year:  2010        PMID: 20797612      PMCID: PMC2931592          DOI: 10.1016/j.chembiol.2010.06.009

Source DB:  PubMed          Journal:  Chem Biol        ISSN: 1074-5521


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