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Gene Review

SRR  -  serine racemase

Homo sapiens

Synonyms: D-serine ammonia-lyase, D-serine dehydratase, ILV1, ISO1, L-serine ammonia-lyase, ...
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Disease relevance of SRR

  • The median effective refractory period of the accessory pathway was 293 msec (interquartile range, 280-310 msec), and the median shortest RR interval between preexcited beats during atrial fibrillation (SRR) [corrected] was 274 msec (240-320 msec) [1].
  • There was no difference between groups for RR, Spo2, incidence or frequency of slow respiratory rate (SRR, 5-min mean RR less than 10) and apneas (AP, greater than or equal to 15 s of less than 100 ml tidal volume), incidence of nausea and/or vomiting, pruritus, or hypotension, and hours asleep or drowsy [2].
  • However, in direct comparisons with non-painters only the excesses for lung cancer (SRR 1.23, 95% CI 1.11 to 1.35, increasing to 1.32, 95% CI 16 to 1.93 with 20 years latency) and bladder cancer (SRR 1.77, 95% CI 1.13 to 2.77) were confirmed [3].
  • Lymphohematopoietic cancer incidence was higher in the coke plants (SRR = 3.46, 95% CI = 1.02-8.91) and stomach cancer incidence was higher in the maintenance departments (SRR = 1.66, 95% CI = 1.05-2.56) [4].
  • At least 1 apnea (tidal volume < 100 mL for > or = 15 sec) occurred in 77% of subjects, and 32% had > or = 1 slow respiratory rate (SRR; 5-min RR < 10 beats/min) episode [5].

Psychiatry related information on SRR

  • Alcohol's Stress-Response-Dampening (SRD) effect has been the subject of much research, but little has been done to examine the effects of drinking alcohol after experiencing a stressor (Stress-Response-Recovery; SRR) [6].

High impact information on SRR

  • Here, we review recent data and discuss the 'synaptic re-entry reinforcement' (SRR) hypothesis, which can account for the role of the hippocampus in memory consolidation at both the molecular and systems levels [7].
  • The central idea of the SRR hypothesis is that reactivation of neural ensembles in the hippocampus during the consolidation period results in multiple rounds of NMDA-receptor-dependent synaptic reinforcement of the hippocampal memory traces created during initial learning [7].
  • In addition, the percentage of D-serine in the total serine in the schizophrenic patients was significantly (z = -4.78, P<.001) lower than that of controls, suggesting that the activity of serine racemase, an enzyme catalyzing the formation of D-serine from L-serine, may have been reduced in the schizophrenic patients [8].
  • Gel-shift analysis of nuclear extracts from hypoxic MPs and HeLa cells demonstrated increased DNA-binding activity at the serum response region (SRR; -111/+14 bp) of the tissue factor promoter at Egr-1 motifs [9].
  • In three nondiscriminator patients with familial isolated vitamin E deficiency, the fractional disappearance rates (mean +/- SD) of deuterium-labeled RRR- and SRR-alpha-tocopherols in plasma were 1.4 +/- 0.6 and 1.3 +/- 0.3 pools per day, respectively (difference, 0.1 +/- 0.3) [10].

Chemical compound and disease context of SRR


Biological context of SRR

  • The SRR gene was localized on chromosome 17q13 [13].
  • We have also evaluated the effects of the chronic administration of MK-801 (0.4 mg/kg) on the gene expression of serine racemase and DAO and on the d-serine concentrations [14].
  • There is new and convincing evidence that the mammalian X chromosome, as well as the Y chromosome, contains an atypically high proportion of genes involved in sex and reproduction (SRR genes) [15].
  • RESULTS: Genomic analyses revealed that human brain SRR transcripts consist of four isoforms with one major species, which were derived from alternative use of various 5' end exons [16].
  • Single nucleotide polymorphisms (SNPs) in SRR and DAO were tested for their association with schizophrenia in both case-control and family-based designs and for correlation with serum levels of D-serine [16].

Anatomical context of SRR


Associations of SRR with chemical compounds


Physical interactions of SRR


Regulatory relationships of SRR


Other interactions of SRR

  • METHODS: Expression of serine racemase in placenta was determined by reverse transcriptase polymerase chain reaction and northern analysis and confirmed by subsequent cloning [22].
  • Effects of MK-801 on the expression of serine racemase and d-amino acid oxidase mRNAs and on the d-serine levels in rat brain [14].
  • Though the three LTK proteins showed high homology, the region that most distinguished LTK1 from LTK2 and LTK3 was found in the extracellular domain, in the SRR [23].
  • Lung cancer morbidity was significantly elevated at the affiliated plants versus the parent plants (SRR = 2.35, 95% CI = 1.07-4.92), and all-cancer morbidity was significantly elevated for maintenance workers compared to office and production workers (SRR = 1.27, 95% CI = 1.00-1.60) [4].
  • Hemispheric asymmetry of EDA-2 pathway, which is represented by shorter SRR latency in the right hand of the right hand responders, was also distorted with CPEMFs [24].

Analytical, diagnostic and therapeutic context of SRR


  1. Prognostic value of electrophysiology testing in asymptomatic patients with Wolff-Parkinson-White pattern. Leitch, J.W., Klein, G.J., Yee, R., Murdock, C. Circulation (1990) [Pubmed]
  2. A comparison of epidural and intramuscular morphine in patients following cesarean section. Daley, M.D., Sandler, A.N., Turner, K.E., Vosu, H., Slavchenko, P. Anesthesiology (1990) [Pubmed]
  3. Cohort mortality study of 57,000 painters and other union members: a 15 year update. Steenland, K., Palu, S. Occupational and environmental medicine. (1999) [Pubmed]
  4. Cancer morbidity in iron and steel workers in Korea. Ahn, Y.S., Park, R.M., Stayner, L., Kang, S.K., Jang, J.K. Am. J. Ind. Med. (2006) [Pubmed]
  5. Oxygenation and ventilation characteristics of thoracic surgical patients the night before surgery. Norman, P.H., Daley, M.D., Sandler, A.N. J. Cardiothorac. Vasc. Anesth. (1994) [Pubmed]
  6. Effects of alcohol consumption on the prevention and alleviation of stress-reactions. Noel, N.E., Lisman, S.A., Schare, M.L., Maisto, S.A. Addictive behaviors. (1992) [Pubmed]
  7. An emerging molecular and cellular framework for memory processing by the hippocampus. Wittenberg, G.M., Tsien, J.Z. Trends Neurosci. (2002) [Pubmed]
  8. Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia. Hashimoto, K., Fukushima, T., Shimizu, E., Komatsu, N., Watanabe, H., Shinoda, N., Nakazato, M., Kumakiri, C., Okada, S., Hasegawa, H., Imai, K., Iyo, M. Arch. Gen. Psychiatry (2003) [Pubmed]
  9. Tissue factor transcription driven by Egr-1 is a critical mechanism of murine pulmonary fibrin deposition in hypoxia. Yan, S.F., Zou, Y.S., Gao, Y., Zhai, C., Mackman, N., Lee, S.L., Milbrandt, J., Pinsky, D., Kisiel, W., Stern, D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  10. Human plasma vitamin E kinetics demonstrate rapid recycling of plasma RRR-alpha-tocopherol. Traber, M.G., Ramakrishnan, R., Kayden, H.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  11. Neurobiology through the looking-glass: D-serine as a new glial-derived transmitter. Wolosker, H., Panizzutti, R., De Miranda, J. Neurochem. Int. (2002) [Pubmed]
  12. Mutual regulation between serine and nitric oxide metabolism in human glioblastoma cells. Shoji, K., Mariotto, S., Ciampa, A.R., Suzuki, H. Neurosci. Lett. (2006) [Pubmed]
  13. Characterization and localization of a human serine racemase. Xia, M., Liu, Y., Figueroa, D.J., Chiu, C.S., Wei, N., Lawlor, A.M., Lu, P., Sur, C., Koblan, K.S., Connolly, T.M. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  14. Effects of MK-801 on the expression of serine racemase and d-amino acid oxidase mRNAs and on the d-serine levels in rat brain. Hashimoto, A., Yoshikawa, M., Andoh, H., Yano, H., Matsumoto, H., Kawaguchi, M., Oka, T., Kobayashi, H. Eur. J. Pharmacol. (2007) [Pubmed]
  15. The X--a sexy chromosome. Graves, J.A., Delbridge, M.L. Bioessays (2001) [Pubmed]
  16. Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and D-serine levels. Yamada, K., Ohnishi, T., Hashimoto, K., Ohba, H., Iwayama-Shigeno, Y., Toyoshima, M., Okuno, A., Takao, H., Toyota, T., Minabe, Y., Nakamura, K., Shimizu, E., Itokawa, M., Mori, N., Iyo, M., Yoshikawa, T. Biol. Psychiatry (2005) [Pubmed]
  17. Ketamine enhances the expression of serine racemase and D-amino acid oxidase mRNAs in rat brain. Takeyama, K., Yoshikawa, M., Oka, T., Kawaguchi, M., Suzuki, T., Hashimoto, A. Eur. J. Pharmacol. (2006) [Pubmed]
  18. Nascent VLDL from liver perfusions of cynomolgus monkeys are preferentially enriched in RRR- compared with SRR-alpha-tocopherol: studies using deuterated tocopherols. Traber, M.G., Rudel, L.L., Burton, G.W., Hughes, L., Ingold, K.U., Kayden, H.J. J. Lipid Res. (1990) [Pubmed]
  19. beta-Carotene transport in human lipoproteins. Comparisons with a-tocopherol. Traber, M.G., Diamond, S.R., Lane, J.C., Brody, R.I., Kayden, H.J. Lipids (1994) [Pubmed]
  20. Serine racemase binds to PICK1: potential relevance to schizophrenia. Fujii, K., Maeda, K., Hikida, T., Mustafa, A.K., Balkissoon, R., Xia, J., Yamada, T., Ozeki, Y., Kawahara, R., Okawa, M., Huganir, R.L., Ujike, H., Snyder, S.H., Sawa, A. Mol. Psychiatry (2006) [Pubmed]
  21. Induction of Serine Racemase by Inflammatory Stimuli Is Dependent on AP-1. Wu, S., Barger, S.W. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  22. Serine racemase and D-serine transport in human placenta and evidence for a transplacental gradient for D-serine in humans. Chen, Z., Huang, W., Srinivas, S.R., Jones, C.R., Ganapathy, V., Prasad, P.D. J. Soc. Gynecol. Investig. (2004) [Pubmed]
  23. The ltk gene family encodes novel receptor-like kinases with temporal expression in developing maize endosperm. Li, Z., Wurtzel, E.T. Plant Mol. Biol. (1998) [Pubmed]
  24. Effect of electromagnetic fields emitted by cellular phones on the latency of evoked electrodermal activity. Esen, F., Esen, H. Int. J. Neurosci. (2006) [Pubmed]
  25. Salvage microdissection testicular sperm extraction after failed conventional testicular sperm extraction in patients with nonobstructive azoospermia. Tsujimura, A., Miyagawa, Y., Takao, T., Takada, S., Koga, M., Takeyama, M., Matsumiya, K., Fujioka, H., Okuyama, A. J. Urol. (2006) [Pubmed]
  26. Analgesic and respiratory effects of epidural sufentanil in patients following thoracotomy. Whiting, W.C., Sandler, A.N., Lau, L.C., Chovaz, P.M., Slavchenko, P., Daley, D., Koren, G. Anesthesiology (1988) [Pubmed]
  27. Optimized expansion of the Wallstent compared with the Palmaz-Schatz stent: on-line observations with two- and three-dimensional intracoronary ultrasound after angiographic guidance. von Birgelen, C., Gil, R., Ruygrok, P., Prati, F., Di Mario, C., van der Giessen, W.J., de Feyter, P.J., Serruys, P.W. Am. Heart J. (1996) [Pubmed]
  28. Study of occupational lung cancer in asbestos factories in China. Zhu, H., Wang, Z. British journal of industrial medicine. (1993) [Pubmed]
  29. Expression of the mRNA and protein of serine racemase in primary cultures of rat neurons. Yoshikawa, M., Nakajima, K., Takayasu, N., Noda, S., Sato, Y., Kawaguchi, M., Oka, T., Kobayashi, H., Hashimoto, A. Eur. J. Pharmacol. (2006) [Pubmed]
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