Serine racemase:: A glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission

被引:677
作者
Wolosker, H
Blackshaw, S
Snyder, SH
机构
[1] Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Dept Pharmacol & Mol Sci, Sch Med, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Dept Psychiat, Sch Med, Baltimore, MD 21205 USA
关键词
D O I
10.1073/pnas.96.23.13409
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Although D amino acids are prominent in bacteria, they generally are thought not to occur in mammals. Recently, high levels of D-serine have been found in mammalian brain where it activates glutamate/N-methyl-D-aspartate receptors by interacting with the "glycine site" of the receptor. Because amino acid racemases are thought to be restricted to bacteria and insects, the origin of D-serine in mammals has been puzzling. We now report cloning and expression of serine racemase, an enzyme catalyzing the formation of D-serine from L-serine, Serine racemase is a protein representing an additional family of pyridoxal-5' phosphate-dependent enzymes in eukaryotes, The enzyme is enriched in rat brain where it occurs in glial cells that possess high levels of D-serine in vivo, Occurrence of serine racemase in the brain demonstrates the conservation of D-amino acid metabolism in mammals with implications for the regulation of N-methyl-D-aspartate neurotransmission through glia-neuronal interactions.
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页码:13409 / 13414
页数:6
相关论文
共 31 条
[1]   Characterization and modelling of VanT:: a novel, membrane-bound, serine racemase from vancomycin-resistant Enterococcus gallinarum BM4174 [J].
Arias, CA ;
Martín-Martinez, M ;
Blundell, TL ;
Arthur, M ;
Courvalin, P ;
Reynolds, PE .
MOLECULAR MICROBIOLOGY, 1999, 31 (06) :1653-1664
[2]   Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses [J].
Berger, AJ ;
Dieudonné, S ;
Ascher, P .
JOURNAL OF NEUROPHYSIOLOGY, 1998, 80 (06) :3336-3340
[3]   OPTIMIZED SURVIVAL OF HIPPOCAMPAL-NEURONS IN B27-SUPPLEMENTED NEUROBASAL(TM), A NEW SERUM-FREE MEDIUM COMBINATION [J].
BREWER, GJ ;
TORRICELLI, JR ;
EVEGE, EK ;
PRICE, PJ .
JOURNAL OF NEUROSCIENCE RESEARCH, 1993, 35 (05) :567-576
[4]  
CHOI DW, 1990, ANNU REV NEUROSCI, V13, P171, DOI 10.1146/annurev.neuro.13.1.171
[5]   BACTERIAL GLUTAMATE RACEMASE HAS HIGH SEQUENCE SIMILARITY WITH MYOGLOBINS AND FORMS AN EQUIMOLAR INACTIVE COMPLEX WITH HEMIN [J].
CHOI, SY ;
ESAKI, N ;
ASHIUCHI, M ;
YOSHIMURA, T ;
SODA, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (21) :10144-10147
[6]   D-AMINO ACIDS IN ANIMALS [J].
CORRIGAN, JJ .
SCIENCE, 1969, 164 (3876) :142-+
[7]  
DANIELLO A, 1993, J BIOL CHEM, V268, P26941
[8]  
Danysz W, 1998, PHARMACOL REV, V50, P597
[9]   NITRIC-OXIDE MEDIATES GLUTAMATE NEUROTOXICITY IN PRIMARY CORTICAL CULTURES [J].
DAWSON, VL ;
DAWSON, TM ;
LONDON, ED ;
BREDT, DS ;
SNYDER, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (14) :6368-6371
[10]   THE PRESENCE OF FREE D-ASPARTIC ACID IN RODENTS AND MAN [J].
DUNLOP, DS ;
NEIDLE, A ;
MCHALE, D ;
DUNLOP, DM ;
LAJTHA, A .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 141 (01) :27-32