Disease relevance of Srr

• Regulation of serine racemase activity by D-serine and nitric oxide in human glioblastoma cells [1].
• AIM: To study the alterations of the expressions of serine racemase in C57BL/6 mouse brain after permanent focal cerebral ischemia [2].
• However, delayed transient decreases of serine racemase in both mRNA and protein levels were detected from d 6 to d 10 after ischemia [2].

High impact information on Srr

• Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine [3].
• We now report that SR is a bifunctional enzyme, producing both d-serine and pyruvate in cultured cells and in vitro [3].
• Transfection of SR into HEK 293 cells elicits synthesis of d-serine and augmented release of pyruvate to culture media [3].
• Serine racemase catalyzes robust elimination of l-serine O-sulfate that is 500 times faster than the physiological racemization reaction, generating sulfate, ammonia, and pyruvate [4].
• Serine racemase is a protein representing an additional family of pyridoxal-5' phosphate-dependent enzymes in eukaryotes [5].

Biological context of Srr

• We identify the human serine racemase genomic structure and show that the gene encompasses seven exons and localizes to chromosome 17q13 [6].
• Allosteric regulation of mouse brain serine racemase [7].
• METHODS: The mRNA level and the protein level of serine racemase were assayed by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively [2].

Anatomical context of Srr

• Finally, activation of brain SR as a result of the changes in calcium concentration was studied in primary astrocytes [8].
• Northern-blot analysis show high levels of human serine racemase in areas known to contain large amounts of endogenous D-serine, such as hippocampus and corpus callosum [6].
• Golga3 and serine racemase co-localized at the cytosol, perinuclear Golgi region, and neuronal and glial cell processes in primary cultures [9].
• RT-PCR and immunoblotting showed that serine racemase (SR), the synthesizing enzyme for d-serine, is expressed in the rMC-1 M??ller cell line and primary cultures of mouse M??ller cells (1 degrees MCs) [10].
• At early stage after middle cerebral artery occlusion (MCAO), no significant change in expression of serine racemase was observed in temporoparietal cortex in ipsilateral hemisphere [2].

Associations of Srr with chemical compounds

• As much as three molecules of pyruvate are synthesized for each molecule of d-serine produced by SR [3].
• Reagents that react with sulfhydryl groups, such as cystamine, were potent inhibitors of SR, in a clear reflection that one or more cysteine residues are important for enzyme activity [8].
• The addition of EDTA to a calcium-saturated serine racemase evokes a profound conformational change, as monitored by both fluorescence and circular dichroism techniques [8].
• Racemization of serine is catalyzed by serine racemase, a pyridoxal 5'-phosphate-dependent enzyme expressed mainly in brain and liver [11].
• Dual substrate and reaction specificity in mouse serine racemase: identification of high-affinity dicarboxylate substrate and inhibitors and analysis of the beta-eliminase activity [12].

Other interactions of Srr

• NMDA receptor overactivation has been implicated in a number of pathological conditions and inhibitors of serine racemase are thus potentially interesting targets for therapy [11].
• Spatiotemporal relationships among D-serine, serine racemase, and D-amino acid oxidase during mouse postnatal development [13].

Analytical, diagnostic and therapeutic context of Srr

• Gel filtration of the recombinant SR revealed the protein to be in a dimer-tetramer equilibrium [8].
• A good agreement was achieved between the developed CE method and the previously established HPLC method for determination of the inhibition constant, K(i), of a new SR inhibitor, L-erythro-3-hydroxyaspartate [14].
• Capillary electrophoresis method for determination of D-serine and its application for monitoring of serine racemase activity [14].
• The protein levels of serine racemase were examined by Western blot [13].

References