Genomes and Genes
racemases and epimerases
Summary: Enzymes that catalyze inversion of the configuration around an asymmetric carbon in a substrate having one (racemase) or more (epimerase) center(s) of asymmetry. (Dorland, 28th ed) EC 5.1.
- Crellin P, Brammananth R, Coppel R. Decaprenylphosphoryl-?-D-ribose 2'-epimerase, the target of benzothiazinones and dinitrobenzamides, is an essential enzyme in Mycobacterium smegmatis. PLoS ONE. 2011;6:e16869 pubmed publisher..Overall, this study further validates DprE1 as a promising target for new anti-mycobacterial drugs. ..
- Yamada H, Tsuzuki T, Maeda N, Yamauchi Y, Yoshida S, Ishida R, et al. Alpha methylacyl-CoA racemase (AMACR) in prostate adenocarcinomas from Japanese patients: is AMACR a "race"-dependent marker?. Prostate. 2013;73:54-9 pubmed publisher..Pathologists should be cautious while interpreting AMACR expression pattern in Japanese patients. ..
- Kumaresan K, Kakkar N, Verma A, Mandal A, Singh S, Joshi K. Diagnostic utility of ?-methylacyl CoA racemase (P504S) & HMWCK in morphologically difficult prostate cancer. Diagn Pathol. 2010;5:83 pubmed publisher..Although, in this study the sensitivity and specificity of HMWCK and AMACR were high, yet it should be used with caution, keeping in mind all their pitfalls and limitations. ..
- Pasca M, Degiacomi G, Ribeiro A, Zara F, De Mori P, Heym B, et al. Clinical isolates of Mycobacterium tuberculosis in four European hospitals are uniformly susceptible to benzothiazinones. Antimicrob Agents Chemother. 2010;54:1616-8 pubmed publisher..All 240 strains were susceptible, thus establishing the baseline prior to the introduction of BTZ043 in clinical trials. ..
- Guzman G, Wu S, Kajdacsy Balla A, Cotler S. Alpha-methylacyl-CoA racemase (AMACR/P504S) can distinguish hepatocellular carcinoma and dysplastic hepatocytes from benign nondysplastic hepatocytes. Appl Immunohistochem Mol Morphol. 2006;14:411-6 pubmed..Prospective studies are needed to determine whether staining for AMACR can distinguish HCC or dysplasia in cytologic and small histologic specimens. ..
- Verrall L, Walker M, Rawlings N, Benzel I, Kew J, Harrison P, et al. d-Amino acid oxidase and serine racemase in human brain: normal distribution and altered expression in schizophrenia. Eur J Neurosci. 2007;26:1657-69 pubmed..However, they raise further questions as to the roles of D-amino acid oxidase and serine racemase in both physiological and pathophysiological processes in the brain. ..
- Marx A, Simon P, Simon R, Mirlacher M, Izbicki J, Yekebas E, et al. AMACR expression in colorectal cancer is associated with left-sided tumor localization. Virchows Arch. 2008;453:243-8 pubmed publisher..We hypothesize that the association of AMACR expression with tumor localization may be related to differences in the metabolism/exposure to fatty acids occurring along the colon. ..
- Pértega Gomes N, Vizcaíno J, Gouveia C, Jeronimo C, Henrique R, Lopes C, et al. Monocarboxylate transporter 2 (MCT2) as putative biomarker in prostate cancer. Prostate. 2013;73:763-9 pubmed publisher..Also, we wanted to evaluate the value of using MCT2 in combination with AMACR and the negative markers 34?E12 or p63 to detect prostate cancer...
- Bendikov I, Nadri C, Amar S, Panizzutti R, De Miranda J, Wolosker H, et al. A CSF and postmortem brain study of D-serine metabolic parameters in schizophrenia. Schizophr Res. 2007;90:41-51 pubmed..Our results suggest that reduced brain serine racemase and elevated D-amino acid oxidase protein levels may contribute to the lower CSF D-serine levels in schizophrenia. ..
- Dorer R, Odze R. AMACR immunostaining is useful in detecting dysplastic epithelium in Barrett's esophagus, ulcerative colitis, and Crohn's disease. Am J Surg Pathol. 2006;30:871-7 pubmed..AMACR is involved in the neoplastic progression in BE and IBD. The high degree of specificity of AMACR for dysplasia/carcinoma in BE and IBD suggests that it may be useful to detect neoplastic epithelium in these conditions. ..
- Daugherty S, Shugart Y, Platz E, Fallin M, Isaacs W, Pfeiffer R, et al. Polymorphic variants in alpha-methylacyl-CoA racemase and prostate cancer. Prostate. 2007;67:1487-97 pubmed..The protective associations observed among ibuprofen users suggest that AMACR gene variants may enhance the chemopreventive effects of ibuprofen on prostate cancer risk. ..
- Yoshikawa M, Nakajima K, Takayasu N, Noda S, Sato Y, Kawaguchi M, et al. Expression of the mRNA and protein of serine racemase in primary cultures of rat neurons. Eur J Pharmacol. 2006;548:74-6 pubmed..These data are the first to demonstrate that a substantial amount of serine racemase exists in the cultured neurons. ..
- Cho E, Kim K, Park C, Kim J, Sohn T, Kim D. AMACR is highly expressed in gastric adenomas and intestinal-type carcinomas. APMIS. 2007;115:713-8 pubmed
- Stewart J, Fleshner N, Cole H, Sweet J. Comparison of annexin II, p63 and alpha-methylacyl-CoA racemase immunoreactivity in prostatic tissue: a tissue microarray study. J Clin Pathol. 2007;60:773-80 pubmed..Immunohistochemical staining for ANXII is a consistent and reliable marker of prostatic neoplasia. The findings of this study suggest the potential utility of ANXII as a diagnostic aid in prostate cancer histopathology. ..
- Manina G, Pasca M, Buroni S, De Rossi E, Riccardi G. Decaprenylphosphoryl-?-D-ribose 2'-epimerase from Mycobacterium tuberculosis is a magic drug target. Curr Med Chem. 2010;17:3099-108 pubmed..The heteromeric decaprenylphosphoryl-?-D-ribose 2'-epimerase thus represents a valid vulnerable antimycobacterial drug target which could result in "magic" for tuberculosis treatment. ..
- Prior C, Guillen Grima F, Robles J, Rosell D, Fernandez Montero J, Agirre X, et al. Use of a combination of biomarkers in serum and urine to improve detection of prostate cancer. World J Urol. 2010;28:681-6 pubmed publisher..1, 96.6, 88.9, and 82.4%, respectively. We conclude that analysis of this biomarker combination in body fluids improves very significantly the diagnosis of PCa compared to the PSA test. ..
- Häggarth L, Hägglöf C, Jaraj S, Wester K, Ponten F, Ostman A, et al. Diagnostic biomarkers of prostate cancer. Scand J Urol Nephrol. 2011;45:60-7 pubmed publisher..AMACR is an accurate diagnostic tissue marker for PC. However, in some PCs AMACR is false negative and a panel of CYCS, ICK and IKBKB may serve as ancillary diagnostic tool. ..
- Sasabe J, Chiba T, Yamada M, Okamoto K, Nishimoto I, Matsuoka M, et al. D-serine is a key determinant of glutamate toxicity in amyotrophic lateral sclerosis. EMBO J. 2007;26:4149-59 pubmed..Collectively, Glu toxicity enhanced by D-Ser overproduced in glia is proposed as a novel mechanism underlying ALS motoneuronal death, and this mechanism may be regarded as a potential therapeutic target for ALS. ..
- Wolosker H. NMDA receptor regulation by D-serine: new findings and perspectives. Mol Neurobiol. 2007;36:152-64 pubmed..In this review, I discuss recent advances in the field and propose a novel model of D-serine signaling that includes a bidirectional flow of D-serine between astrocytes and neurons. ..
- Wright J, Neuhouser M, Lin D, Kwon E, Feng Z, Ostrander E, et al. AMACR polymorphisms, dietary intake of red meat and dairy and prostate cancer risk. Prostate. 2011;71:498-506 pubmed publisher..These findings suggest that the effects of AMACR polymorphisms and red meat and dairy on PCa risk are independent. ..
- Murphy A, Hughes C, Lannigan G, Sheils O, O LEARY J, Loftus B. Heterogeneous expression of alpha-methylacyl-CoA racemase in prostatic cancer correlates with Gleason score. Histopathology. 2007;50:243-51 pubmed..Positive staining in BPH is also documented, thus emphasizing the importance of interpreting AMACR immunohistochemistry in the context of other findings in a diagnostic setting. ..
- Labrie V, Fukumura R, Rastogi A, Fick L, Wang W, Boutros P, et al. Serine racemase is associated with schizophrenia susceptibility in humans and in a mouse model. Hum Mol Genet. 2009;18:3227-43 pubmed publisher..Furthermore, analysis of SRR genetic variants in humans identified a robust association with schizophrenia. This study demonstrates that aberrant Srr function and diminished d-serine may contribute to schizophrenia pathogenesis. ..
- Balan L, Foltyn V, Zehl M, Dumin E, Dikopoltsev E, Knoh D, et al. Feedback inactivation of D-serine synthesis by NMDA receptor-elicited translocation of serine racemase to the membrane. Proc Natl Acad Sci U S A. 2009;106:7589-94 pubmed publisher..We propose that the inhibition of D-serine synthesis caused by translocation of SR to the membrane provides a fail-safe mechanism to prevent NMDAR overactivation in vicinal cells or synapses. ..
- Mustafa A, van Rossum D, Patterson R, Maag D, Ehmsen J, Gazi S, et al. Glutamatergic regulation of serine racemase via reversal of PIP2 inhibition. Proc Natl Acad Sci U S A. 2009;106:2921-6 pubmed publisher..Thus mutants of SR that cannot bind PIP2 lose their membrane localizations and display a 4-fold enhancement of catalytic activity. Moreover, mGluR5 activation of SR activity is abolished by inhibiting phospholipase C. ..
- Trefzer C, Rengifo Gonzalez M, Hinner M, Schneider P, Makarov V, Cole S, et al. Benzothiazinones: prodrugs that covalently modify the decaprenylphosphoryl-?-D-ribose 2'-epimerase DprE1 of Mycobacterium tuberculosis. J Am Chem Soc. 2010;132:13663-5 pubmed publisher..Here we demonstrate that BTZs are activated in the bacterium by reduction of an essential nitro group to a nitroso derivative, which then specifically reacts with a cysteine residue in the active site of DprE1. ..
- Dun Y, Duplantier J, Roon P, Martin P, Ganapathy V, Smith S. Serine racemase expression and D-serine content are developmentally regulated in neuronal ganglion cells of the retina. J Neurochem. 2008;104:970-8 pubmed..This represents the first report of neuronal expression of D-serine and serine racemase in the vertebrate retina and suggests an important contribution of neuronal D-serine during retinal development. ..
- Christophe T, Jackson M, Jeon H, Fenistein D, Contreras Dominguez M, Kim J, et al. High content screening identifies decaprenyl-phosphoribose 2' epimerase as a target for intracellular antimycobacterial inhibitors. PLoS Pathog. 2009;5:e1000645 pubmed publisher..Beyond validating the high throughput/content screening approach, our results open new avenues for finding the next generation of antimicrobials. ..
- Turpin F, Potier B, Dulong J, Sinet P, Alliot J, Oliet S, et al. Reduced serine racemase expression contributes to age-related deficits in hippocampal cognitive function. Neurobiol Aging. 2011;32:1495-504 pubmed publisher..Understanding the processes that specifically affect serine racemase during aging could thus provide key insights into the treatment of memory deficits in the elderly. ..
- Wolosker H. Serine racemase and the serine shuttle between neurons and astrocytes. Biochim Biophys Acta. 2011;1814:1558-66 pubmed publisher..SR and the serine shuttle pathway are therapeutic targets in neurodegenerative diseases in which NMDA receptor dysfunction plays pathological roles. This article is part of a Special Issue entitled: Pyridoxal Phospate Enzymology. ..
- Inoue R, Hashimoto K, Harai T, Mori H. NMDA- and beta-amyloid1-42-induced neurotoxicity is attenuated in serine racemase knock-out mice. J Neurosci. 2008;28:14486-91 pubmed publisher..The control of SR activity and D-serine level in the brain may lead to a novel strategy for neuroprotection against various neurodegenerative diseases. ..
- Kalyanaraman C, Imker H, Fedorov A, Fedorov E, Glasner M, Babbitt P, et al. Discovery of a dipeptide epimerase enzymatic function guided by homology modeling and virtual screening. Structure. 2008;16:1668-77 pubmed publisher..Subsequently, crystal structures of the enzyme were determined in complex with three substrates, showing close agreement with the computational models and revealing the structural basis for the observed substrate selectivity. ..
- Lisovsky M, Falkowski O, Bhuiya T. Expression of alpha-methylacyl-coenzyme A racemase in dysplastic Barrett's epithelium. Hum Pathol. 2006;37:1601-6 pubmed..Further validation and prospective studies are warranted. ..
- Zhang C, Montironi R, MacLennan G, Lopez Beltran A, Li Y, Tan P, et al. Is atypical adenomatous hyperplasia of the prostate a precursor lesion?. Prostate. 2011;71:1746-51 pubmed publisher..Our data provide additional evidence linking AAH to prostatic adenocarcinoma. ..
- Huang W, Zhao J, Li L, Huang Y, Yang X, Wang J, et al. a-Methylacyl coenzyme A racemase is highly expressed in the intestinal-type adenocarcinoma and high-grade dysplasia lesions of the stomach. Histol Histopathol. 2008;23:1315-20 pubmed publisher..The high level expression of AMACR in high-grade dysplasia and carcinoma suggests that it may be a useful biomarker in distinguishing high-grade dysplasia and carcinoma from low-grade dysplasia. ..
- Lee W. Alpha-methylacyl-CoA-racemase expression in adenocarcinoma, dysplasia and non-neoplastic epithelium of the stomach. Oncology. 2006;71:246-50 pubmed..It also suggests that AMACR expression is more likely to be associated with intestinal-type adenocarcinoma in gastric carcinogenesis. ..
- Morita Y, Ujike H, Tanaka Y, Otani K, Kishimoto M, Morio A, et al. A genetic variant of the serine racemase gene is associated with schizophrenia. Biol Psychiatry. 2007;61:1200-3 pubmed..The IVS1a+465C allele of the SRR gene, which reduces expression of the gene, is a risk factor for schizophrenia, especially the paranoid subtype. ..
- Scarpelli M, Mazzucchelli R, Barbisan F, Santinelli A, Lopez Beltran A, Cheng L, et al. Is there a role for prostate tumour overexpressed-1 in the diagnosis of HGPIN and of prostatic adenocarcinoma? A comparison with alpha-methylacyl CoA racemase. Int J Immunopathol Pharmacol. 2012;25:67-74 pubmed..However, PTOV1 may aid in the diagnosis of PCa, at least to supplement AMACR as another positive marker of carcinoma and to potentially increase diagnostic accuracy...
- Hikida T, Mustafa A, Maeda K, Fujii K, Barrow R, Saleh M, et al. Modulation of D-serine levels in brains of mice lacking PICK1. Biol Psychiatry. 2008;63:997-1000 pubmed publisher..PICK1 may be involved in the regulation of brain D-serine levels and SR in a spatially and temporally specific manner. ..
- Carnell A, Hale I, Denis S, Wanders R, Isaacs W, Wilson B, et al. Design, synthesis, and in vitro testing of alpha-methylacyl-CoA racemase inhibitors. J Med Chem. 2007;50:2700-7 pubmed
- Schostak M, Miller K, Krause H, Schrader M, Kempkensteffen C, Kollermann J. Kinetic fluorescence reverse transcriptase-polymerase chain reaction for alpha-methylacyl CoA racemase distinguishes prostate cancer from benign lesions. Cancer Detect Prev. 2006;30:449-54 pubmed..Since the latter clearly predominate in the laboratory routine, PCR-based detection of AMACR has the potential to gain widespread acceptance as a suitable future tool for monitoring prostate cancer patients. ..
- Lloyd M, Darley D, Wierzbicki A, Threadgill M. Alpha-methylacyl-CoA racemase--an 'obscure' metabolic enzyme takes centre stage. FEBS J. 2008;275:1089-102 pubmed publisher..These recent advances enable new preventative and treatment strategies for cancer. ..
- Kaić G, Tomasović Loncarić C. Alpha-methylacyl-CoA racemase (AMACR) in fine-needle aspiration specimens of prostate lesions. Diagn Cytopathol. 2009;37:803-8 pubmed publisher..P504S/AMACR staining might be of great value in cytodiagnosis of prostate lesions as well as an example of the characterization of cells at the molecular level using fresh tissue obtained by fine-needle aspiration. ..
- Takayasu N, Yoshikawa M, Watanabe M, Tsukamoto H, Suzuki T, Kobayashi H, et al. The serine racemase mRNA is expressed in both neurons and glial cells of the rat retina. Arch Histol Cytol. 2008;71:123-9 pubmed..These results suggest that both the neuron- and glia-derived D-serine could modulate neurotransmission via the glycine site of the N-methyl-D-aspartate receptors in the retina. ..
- Thompson S, Calvin J, Hogg S, Ferdinandusse S, Wanders R, Barker R. Relapsing encephalopathy in a patient with alpha-methylacyl-CoA racemase deficiency. J Neurol Neurosurg Psychiatry. 2008;79:448-50 pubmed..This case adds to the phenotypic variation seen in this peroxisomal disorder and highlights the importance of screening for plasma pristanic acid levels in patients with unexplained relapsing encephalopathies. ..
- Daugherty S, Platz E, Shugart Y, Fallin M, Isaacs W, Chatterjee N, et al. Variants in the alpha-Methylacyl-CoA racemase gene and the association with advanced distal colorectal adenoma. Cancer Epidemiol Biomarkers Prev. 2007;16:1536-42 pubmed..05). Our study identified variants in AMACR associated with advanced distal colorectal adenoma and pointed to potential interactions with ibuprofen use. ..
- Kristiansen G, Fritzsche F, Wassermann K, Jager C, Tölls A, Lein M, et al. GOLPH2 protein expression as a novel tissue biomarker for prostate cancer: implications for tissue-based diagnostics. Br J Cancer. 2008;99:939-48 pubmed publisher..Further, GOLPH2 upregulation was detected in 26 of 31 (84%) AMACR-negative prostate cancer cases. These data clearly suggest GOLPH2 as an additional ancillary positive marker for tissue-based diagnosis of prostate cancer. ..
- Shah R, Tadros Y, Brummell B, Zhou M. The diagnostic use of ERG in resolving an "atypical glands suspicious for cancer" diagnosis in prostate biopsies beyond that provided by basal cell and ?-methylacyl-CoA-racemase markers. Hum Pathol. 2013;44:786-94 pubmed publisher..We recommend judicious use of ERG, preferably as a component of multiplex IHC, in evaluation of difficult prostate biopsies. ..
- Ouyang B, Bracken B, Burke B, Chung E, Liang J, Ho S. A duplex quantitative polymerase chain reaction assay based on quantification of alpha-methylacyl-CoA racemase transcripts and prostate cancer antigen 3 in urine sediments improved diagnostic accuracy for prostate cancer. J Urol. 2009;181:2508-13; discussion 2513-4 pubmed publisher..Their combined use in a dual marker test further improved sensitivity and accuracy, and could serve as a surveillance test after repeat negative prostate biopsies. ..
- Horio M, Kohno M, Fujita Y, Ishima T, Inoue R, Mori H, et al. Levels of D-serine in the brain and peripheral organs of serine racemase (Srr) knock-out mice. Neurochem Int. 2011;59:853-9 pubmed publisher..These results suggest that SRR is the major enzyme responsible for D-serine production in the mouse forebrain, and that other pathways of d-serine production may exist in the brain and peripheral organs. ..
- Steffek A, Haroutunian V, Meador Woodruff J. Serine racemase protein expression in cortex and hippocampus in schizophrenia. Neuroreport. 2006;17:1181-5 pubmed
- Marx A, Wandrey T, Simon P, Wewer A, Grob T, Reichelt U, et al. Combined alpha-methylacyl coenzyme A racemase/p53 analysis to identify dysplasia in inflammatory bowel disease. Hum Pathol. 2009;40:166-73 pubmed publisher..It is concluded that combined alpha-methylacyl coenzyme A racemase/p53 analysis may represent a helpful tool to confirm dysplasia in inflammatory bowel disease. ..
- Puyal J, Martineau M, Mothet J, Nicolas M, Raymond J. Changes in D-serine levels and localization during postnatal development of the rat vestibular nuclei. J Comp Neurol. 2006;497:610-21 pubmed..The strong decrease of D-serine levels and the glial-to-neuronal switch suggests that D-serine may have distinct functional roles depending on the developmental stage of the vestibular network. ..
- Baumgart F, Mancheno J, Rodríguez Crespo I. Insights into the activation of brain serine racemase by the multi-PDZ domain glutamate receptor interacting protein, divalent cations and ATP. FEBS J. 2007;274:4561-71 pubmed
- Trpkov K, Bartczak McKay J, Yilmaz A. Usefulness of cytokeratin 5/6 and AMACR applied as double sequential immunostains for diagnostic assessment of problematic prostate specimens. Am J Clin Pathol. 2009;132:211-20; quiz 307 pubmed publisher..Double immunohistochemical staining for CK5/6 and AMACR is a simple assay to perform and may be used as an alternative to antibody cocktails for routine evaluation of problematic prostate specimens. ..
- Ng V, Koh M, Tan S, Tan P. Is triple immunostaining with 34betaE12, p63, and racemase in prostate cancer advantageous? A tissue microarray study. Am J Clin Pathol. 2007;127:248-53 pubmed..6% for p63, 34betaE12, and AMACR, respectively. The triple cocktail offers a cost-effective way of evaluating abnormal prostatic glandular foci, in addition to maximizing the use of small tissue samples from prostatic needle biopsies. ..
- Mustafa A, Kumar M, Selvakumar B, Ho G, Ehmsen J, Barrow R, et al. Nitric oxide S-nitrosylates serine racemase, mediating feedback inhibition of D-serine formation. Proc Natl Acad Sci U S A. 2007;104:2950-5 pubmed..These findings support a model whereby postsynaptic stimulation of nitric-oxide (NO) formation feeds back to presynaptic cells to S-nitrosylate SR and decrease D-serine availability to postsynaptic NMDA receptors. ..
- Shi X, Gong E, Wu X. Alpha-methylacyl-CoA racemase/P504S overexpression in colorectal carcinoma is correlated with tumor differentiation. Appl Immunohistochem Mol Morphol. 2007;15:175-80 pubmed..No relation was found between AMACR expression and overall survival. Our findings support the view that the expression of AMACR in CRC is correlated with tumor differentiation. ..
- Wolosker H, Mori H. Serine racemase: an unconventional enzyme for an unconventional transmitter. Amino Acids. 2012;43:1895-904 pubmed publisher..Here, we review the mechanisms of D-serine synthesis by serine racemase and discuss the lessons we can learn from serine racemase knockout mice, focusing on the roles attributed to D-serine and its cellular origin. ..
- Levin A, Zuhlke K, Ray A, Cooney K, Douglas J. Sequence variation in alpha-methylacyl-CoA racemase and risk of early-onset and familial prostate cancer. Prostate. 2007;67:1507-13 pubmed..These findings emphasize the value of studying early-onset and familial prostate cancer when attempting to identify genetic variation associated with prostate cancer. ..
- Wu S, Basile A, Barger S. Induction of serine racemase expression and D-serine release from microglia by secreted amyloid precursor protein (sAPP). Curr Alzheimer Res. 2007;4:243-51 pubmed..D-serine may cooperate with glutamate to link neuroinflammation with excitotoxicity, suggesting a pathogenic mechanism applicable to neuronal death in AD and other neurodegenerative diseases. ..