Source:http://linkedlifedata.com/resource/pubmed/id/15536068
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2005-1-17
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pubmed:abstractText |
Mammalian brain contains high levels of d-serine, an endogenous co-agonist of N-methyl D-aspartate type of glutamate receptors. D-Serine is synthesized by serine racemase, a brain enriched enzyme converting L- to D-serine. Degradation of D-serine is achieved by D-amino acid oxidase, but this enzyme is not present in forebrain areas that are highly enriched in D-serine. We now report that serine racemase catalyzes the degradation of cellular D-serine itself, through the alpha,beta-elimination of water. The enzyme also catalyzes water alpha,beta-elimination with L-serine and L-threonine. alpha,beta-Elimination with these substrates is observed both in vitro and in vivo. To investigate further the role of alpha,beta-elimination in regulating cellular D-serine, we generated a serine racemase mutant displaying selective impairment of alpha,beta-elimination activity (Q155D). Levels of D-serine synthesized by the Q155D mutant are several-fold higher than the wild-type both in vitro and in vivo. This suggests that the alpha,beta-elimination reaction limits the achievable D-serine concentration in vivo. Additional mutants in vicinal residues (H152S, P153S, and N154F) similarly altered the partition between the alpha,beta-elimination and racemization reactions. alpha,beta-Elimination also competes with the reverse serine racemase reaction in vivo. Although the formation of L- from D-serine is readily detected in Q155D mutant-expressing cells incubated with physiological D-serine concentrations, reversal with wild-type serine racemase-expressing cells required much higher D-serine concentration. We propose that alpha,beta-elimination provides a novel mechanism for regulating intracellular D-serine levels, especially in brain areas that do not possess D-amino acid oxidase activity. Extracellular D-serine is more stable toward alpha,beta-elimination, likely due to physical separation from serine racemase and its elimination activity.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Racemases and Epimerases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Water,
http://linkedlifedata.com/resource/pubmed/chemical/serine racemase
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:BendikovInnaI,
pubmed-author:CHUE CEC,
pubmed-author:De MirandaJoariJ,
pubmed-author:DuminElenaE,
pubmed-author:FoltynVeronika NVN,
pubmed-author:KartvelishvilyElenaE,
pubmed-author:PanizzuttiRogerioR,
pubmed-author:ShleperMariaM,
pubmed-author:ToneyMichael DMD,
pubmed-author:WoloskerHermanH
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pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1754-63
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15536068-Adenosine Triphosphate,
pubmed-meshheading:15536068-Amino Acid Sequence,
pubmed-meshheading:15536068-Catalysis,
pubmed-meshheading:15536068-Cell Line,
pubmed-meshheading:15536068-Humans,
pubmed-meshheading:15536068-Molecular Sequence Data,
pubmed-meshheading:15536068-Mutagenesis, Site-Directed,
pubmed-meshheading:15536068-Racemases and Epimerases,
pubmed-meshheading:15536068-Recombinant Proteins,
pubmed-meshheading:15536068-Sequence Homology, Amino Acid,
pubmed-meshheading:15536068-Serine,
pubmed-meshheading:15536068-Water
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pubmed:year |
2005
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pubmed:articleTitle |
Serine racemase modulates intracellular D-serine levels through an alpha,beta-elimination activity.
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pubmed:affiliation |
Department of Biochemistry, Technion-Israel Institute of Technology, The B. Rappaport Faculty of Medicine, Haifa 31096, Israel.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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