Read by QxMD icon Read

Serine racemase

Herman Wolosker, Darrick T Balu, Joseph T Coyle
d-Serine modulates N-methyl d-aspartate receptors (NMDARs) and regulates synaptic plasticity, neurodevelopment, and learning and memory. However, the primary site of d-serine synthesis and release remains controversial, with some arguing that it is a gliotransmitter and others defining it as a neuronal cotransmitter. Results from several laboratories using different strategies now show that the biosynthetic enzyme of d-serine, serine racemase (SR), is expressed almost entirely by neurons, with few astrocytes appearing to contain d-serine...
October 11, 2016: Trends in Neurosciences
Akihiro Watanabe, Tsutomu Sasaki, Toshiro Yukami, Hideaki Kanki, Manabu Sakaguchi, Takemori Hiroshi, Kazuo Kitagawa, Hideki Mochizuki
There are no effective neuroprotectant drugs for acute cerebral ischemia. Serine racemase (SR) synthesizes d-serine, which is involved in N-methyl-d-aspartate (NMDA) receptor-induced neurotoxicity. Recently, SR deletion was reported to protect against focal cerebral ischemia. However, regulatory mechanisms controlling SR-activity in the neurovascular unit (NVU) during cerebral ischemia remain to be clarified. We investigated the effects of SR inhibition on neurovascular protection after ischemia. The SR inhibitor phenazine methosulfate (PMS) alleviated neuronal damage in an ex vivo ischemic model (oxygen glucose deprivation [OGD]) using primary neuronal cultures, and in an in vivo mouse model of ischemia (middle cerebral artery occlusion [MCAO])...
September 28, 2016: Neuroscience
Alo C Basu, Matthew D Puhl, Joseph T Coyle
We have used mutant mice to probe the roles of the endogenous co-agonists of the NMDA receptor (NMDAR), D-serine and glycine, in fear learning and memory. Serine racemase knockout (SR-/-) mice have less than 15% of wild type forebrain levels of D-serine, whereas glycine transporter 1 heterozygous knockout (GlyT1+/-) mice have elevated synaptic glycine. While cued fear was normal in both delay and trace conditioned mice of both mutant genotypes, contextual fear was affected in trace conditioned subjects: SR-/- mice showed decreased contextual freezing, whereas GlyT1+/- mice showed elevated contextual freezing...
September 12, 2016: Neurobiology of Learning and Memory
Gourango Talukdar, Ran Inoue, Tomoyuki Yoshida, Tetsuya Ishimoto, Keisuke Yaku, Takashi Nakagawa, Hisashi Mori
BACKGROUND: Serine racemase (SR) catalyzes the production of D-serine, a co-agonist of the N-methyl-D-aspartate receptor (NMDAR). A previous report shows the contribution of SR in the NMDAR-mediated neuronal cell death process. METHODS AND RESULTS: To analyze the intrinsic role of SR in the cell death process, we established the epithelial human embryonic kidney 293T (HEK293T) cell lines expressing wild-type SR (SR-WT), catalytically inactive mutant SR (SR-K56G), and catalytically hyperactive mutant SR (SR-Q155D)...
August 29, 2016: Biochimica et Biophysica Acta
Wisarut Payoungkiattikun, Seiji Okazaki, Atsutoshi Ina, Aran H-Kittikun, Yasuhisa Asano
α-Amino-ε-caprolactam (ACL) racemizing activity was detected in a putative dialkylglycine decarboxylase (EC from Citreicella sp. SE45. The encoding gene of the enzyme was cloned and transformed in Escherichia coli BL21 (DE3). The molecular mass of the enzyme was shown to be 47.4 kDa on SDS-polyacrylamide gel electrophoresis. The enzymatic properties including pH and thermal optimum and stabilities were determined. This enzyme acted on a broad range of amino acid amides, particularly unbranched amino acid amides including L-alanine amide and L-serine amide with a specific activity of 17...
August 20, 2016: Journal of Industrial Microbiology & Biotechnology
Stefano Bruno, Francesco Marchesani, Luca Dellafiora, Marilena Margiotta, Serena Faggiano, Barbara Campanini, Andrea Mozzarelli
Serine racemase catalyzes both the synthesis and the degradation of d-serine, an obligatory co-agonist of the glutamatergic NMDA receptors. It is allosterically controlled by adenosine triphosphate (ATP), which increases its activity around 7-fold through a co-operative binding mechanism. Serine racemase has been proposed as a drug target for the treatment of several neuropathologies but, so far, the search has been directed only toward the active site, with the identification of a few, low-affinity inhibitors...
October 15, 2016: Biochemical Journal
Masumi Katane, Yuki Saitoh, Keita Uchiyama, Kazuki Nakayama, Yasuaki Saitoh, Tetsuya Miyamoto, Masae Sekine, Kouji Uda, Hiroshi Homma
Free d-serine (d-Ser) plays a crucial role in regulating brain function in mammals. In various organisms, including mammals, d-Ser is biosynthesized by Ser racemase, a synthetic enzyme that produces d-Ser from l-Ser. Ser racemase also exhibits dehydratase activity toward several hydroxyamino acids. Thus, this enzyme is unique in that it possesses the capability to both synthesize and degrade d-Ser; however, the physiological significance of its degradative activity remains unclear. In contrast to the physiological roles of d-Ser in mammals, little is known about the role of this amino acid in lower organisms, including the nematode Caenorhabditis elegans...
September 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Tsubasa Washio, Shiro Kato, Tadao Oikawa
We succeeded in expressing the aspartate racemase homolog gene from Thermococcus litoralis DSM 5473 in Escherichia coli Rosetta (DE3) and found that the gene encodes aspartate racemase. The aspartate racemase gene consisted of 687 bp and encoded 228 amino acid residues. The purified enzyme showed aspartate racemase activity with a specific activity of 1590 U/mg. The enzyme was a homodimer with a molecular mass of 56 kDa and did not require pyridoxal 5'-phosphate as a coenzyme. The enzyme showed aspartate racemase activity even at 95 °C, and the activation energy of the enzyme was calculated to be 51...
September 2016: Extremophiles: Life Under Extreme Conditions
Sandra Van der Auwera, Alexander Teumer, Johannes Hertel, Georg Homuth, Uwe Völker, Michael J Lucht, Franziska Degenhardt, Thomas Schulze, Marcella Rietschel, Markus M Nöthen, Ulrich John, Matthias Nauck, Hans Jörgen Grabe
Schizophrenia has a considerable genetic background. Epidemiological studies suggest an inverse clinical association between schizophrenia and migraine. However, it is unclear to what extent this inverse comorbidity can be explained by genetic mechanisms or by schizophrenia-related behavioral factors. For both disorders hypotheses of glutamate N-methyl-D-aspartate (NMDA) receptor dysfunction have been developed in the past. We hypothesized that both conditions share common genetic factors with inverse effects, primary in the glutamatergic system and genes involved in NMDA activation...
September 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Tomokazu Ito, Mika Hayashida, Saki Kobayashi, Natsumi Muto, Ayumi Hayashi, Tohru Yoshimura, Hisashi Mori
d-Aspartate is found in the nervous and reproductive system and participates in various physiological roles. While several lines of evidence suggest that this amino acid has an endogenous origin, the enzyme responsible for mammalian d-Asp biosynthesis has not yet been identified.We show that mammalian serine racemase (SRR), the primary enzyme responsible for brain d-Ser production, catalyzes Asp racemization via a two-base mechanism. We observed that overexpression of SRR in rat pheochromocytoma PC12 cells resulted in an increase in intracellular d-Asp compared to control cells, demonstrating that SRR functions as an Asp racemase in the cells...
July 7, 2016: Journal of Biochemistry
Hongyan Yu, Haisan Zhang, Yongfeng Yang, Wenqiang Li, Hongxing Zhang, Ge Yang, Luxian Lü
OBJECTIVE: To investigate the potential association of carbonic anhydrase I (CA1) anterior pharynx-defective 1A ( APH1A), neurodevelopment protein 1-like 1 (NDEL1) and serine racemase (SRR) gene polymorphisms with the susceptibility of schizophrenia (SZ). METHODS: A case-control study was performed to identify polymorphisms of the CA1, APH1A, NDEL1 and SRR gene that may confer susceptibility to SZ in the Han Chinese population. Five single nucleotide polymorphisms (SNPs) were genotyped in 516 paranoid SZ patients and 516 control subjects by real time quantitative polymerase chain reaction...
December 15, 2015: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Song Cao, Zhi Xiao, Mengjie Sun, Youyan Li
BACKGROUND: The N-methyl-D-aspartate subtype of glutamate receptor plays a critical role in morphine tolerance. D-serine, a co-agonist of N-methyl-D-aspartate receptor, participates in many physiological and pathophysiological processes via regulating N-methyl-D-aspartate receptor activation. The purinergic P2X7 receptor activation can induce the D-serine release in the central nervous system. This study aimed to investigate the role of the ventrolateral midbrain periaqueductal gray D-serine in the mechanism of morphine tolerance in rats...
2016: Molecular Pain
Joseph T Coyle, Darrick T Balu, Matthew D Puhl, Glenn T Konopaske
Nearly 60 years ago Seymour Kety proposed that research on genetics and brain pathology, but not on neurochemistry, would ultimately lead to an understanding of the pathophysiology of schizophrenia. This article will demonstrate the prescience of Kety's proposal; advances in our knowledge of brain structure and genetics have shaped our current understanding of the pathophysiology of schizophrenia. Brain-imaging techniques have shown that schizophrenia is associated with cortical atrophy and ventricular enlargement, which progresses for at least a decade after the onset of psychotic symptoms...
March 2016: Harvard Review of Psychiatry
Hong Lin, Ariel A Jacobi, Stewart A Anderson, David R Lynch
D-serine is an endogenous coagonist at the glycine site of synaptic NMDA receptors (NMDARs), synthesized by serine racemase (SR) through conversion of L-serine. It is crucial for synaptic plasticity and is implicated in schizophrenia. Our previous studies demonstrated specific loss of SR, D-serine-responsive synaptic NMDARs, and glutamatergic synapses in cortical neurons lacking α7 nicotinic acetylcholine receptors, which promotes glutamatergic synapse formation and maturation during development. We thus hypothesize that D-serine and SR (D-serine/SR) are associated with glutamatergic synaptic development...
2016: Frontiers in Cellular Neuroscience
Lingling Zou, Yang Song, Chengliang Wang, Jiaqi Sun, Leilei Wang, Beijiu Cheng, Jun Fan
Serine racemase (SR) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that is responsible for D-serine biosynthesis in vivo. The first X-ray crystal structure of maize SR was determined to 2.1 Å resolution and PLP binding was confirmed in solution by UV-Vis absorption spectrometry. Maize SR belongs to the type II PLP-dependent enzymes and differs from the SR of a vancomycin-resistant bacterium. The PLP is bound to each monomer by forming a Schiff base with Lys67. Structural comparison with rat and fission yeast SRs reveals a similar arrangement of active-site residues but a different orientation of the C-terminal helix...
March 2016: Acta Crystallographica. Section F, Structural Biology Communications
Youguang Pu, Fangfang Zhao, Wenjing Cai, Xianghui Meng, Yinpeng Li, Shanbao Cai
MicroRNAs have been identified as key players in the development and progression of osteosarcoma, which is the most common primary malignancy of bone. Sequencing-based miR-omic and quantitative real-time PCR analyses suggested that the expression of miR-193a-3p and miR-193a-5p was decreased by DNA methylation at their promoter region in a highly metastatic osteosarcoma cell line (MG63.2) relative to their expression in the less metastatic MG63 cell line. Further wound-healing and invasion assays demonstrated that both miR-193a-3p and miR-193a-5p suppressed osteosarcoma cell migration and invasion...
April 2016: Clinical & Experimental Metastasis
Zhi-Qiang Liu, Xun-Hu Gu, Yuan-Jian Yang, Xiao-Ping Yin, Li-Jun Xu, Wei Wang
BACKGROUND: d-serine, the endogenous co-agonist of N-methyl-d-aspartate receptors (NMDARs), is considered to be essential for learning and memory. The aim of the current investigation was to systematically evaluate the role of d-serine on addiction behaviors considered to be mediated by the nucleus accumbens (NAc). METHODS: d-Serine concentration in the NAc was measured by high-performance liquid chromatography (HPLC). Cocaine-induced behavioral sensitization and conditioned place preference (CPP) models were used to evaluate the relation between changes in serine in the nucleus accumbens and cocaine-induced behavioral effects...
April 2016: Pharmacology, Biochemistry, and Behavior
Goren Kolodney, Elena Dumin, Hazem Safory, Dina Rosenberg, Hisashi Mori, Inna Radzishevsky, Herman Wolosker
No abstract text is available yet for this article.
February 5, 2016: Journal of Biological Chemistry
Minoru Tanigawa, Chihiro Suzuki, Kimio Niwano, Rensuke Kanekatsu, Hiroyuki Tanaka, Kihachiro Horiike, Kenji Hamase, Yoko Nagata
The silkworm Bombyx mori contains high concentrations of free D-serine, an optical isomer of L-serine. To elucidate its function, we first investigated the localization of D-serine in various organs of silkworm larvae, pupae, and adult moths. Using immunohistochemical analysis with an anti-D-serine antibody, we found D-serine in the microvilli of midgut goblet and cylindrical cells and in peripheral matrix components of testicular and ovarian cells. By spectrophotometric analysis, D-serine was also found in the hemolymph and fat body...
April 2016: Journal of Insect Physiology
Alan C Foster, Yong-Xin Li, Stephen Runyan, Tim Dinh, Steven Venadas, June Chen, Srinath Pashikanti, Apurba Datta, George Ehring, Ursula Staubli
The enantiomers of erythro-3-hydroxyaspartate were tested for activity at glutamate transporters and NMDA receptors. Both enantiomers inhibited glutamate transporters in rat hippocampal crude synaptosomes and elicited substrate-like activity at EAAT1, 2 and 3 as measured by voltage clamp in the Xenopus oocyte expression system. The enantiomers had similar affinities, but the D-enantiomer showed a lower maximal effect at EAAT1, 2 and 3 than the L-enantiomer. Surprisingly, D-erythro-3-hydroxyaspartate was a potent NMDA receptor agonist with an EC50 value in rat hippocampal neurons of 320nM, whereas the L-enantiomer was 100-fold less potent...
November 12, 2015: Journal of Neurochemistry
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"