The Glycerophospho Metabolome and Its Influence on Amino Acid Homeostasis Revealed by Brain Metabolomics of GDE1(-/-) Mice

被引：38

作者：

Kopp, Florian ^{[1
,2
]}

Komatsu, Toru ^{[1
,2
]}

Nomura, Daniel K. ^{[1
,2
]}

Trauger, Sunia A. ^{[3
,4
]}

Thomas, Jason R. ^{[1
,2
]}

Siuzdak, Gary ^{[3
,4
]}

Simon, Gabriel M. ^{[1
,2
]}

Cravatt, Benjamin F. ^{[1
,2
]}

机构：

[1] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Dept Biol Mol, La Jolla, CA 92037 USA

[4] Scripps Res Inst, Ctr Mass Spectrometry, La Jolla, CA 92037 USA

来源：

CHEMISTRY & BIOLOGY | 2010年 / 17卷 / 08期

基金：

美国国家卫生研究院;

关键词：

TANDEM MASS-SPECTROMETRY; N-ACYL ETHANOLAMINE; ESCHERICHIA-COLI; D-SERINE; SACCHAROMYCES-CEREVISIAE; MOUSE-BRAIN; PHOSPHODIESTERASE; IDENTIFICATION; ENZYME; PATHWAY;

D O I：

10.1016/j.chembiol.2010.06.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：831 / 840

页数：10

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