Disease relevance of Selenomethionine

• Sexually intact elderly male beagle dogs were randomly assigned to receive an unsupplemented diet (control group) or diets that were supplemented with selenium (treatment group), either as selenomethionine or as high-selenium yeast at 3 micro g/kg or 6 micro g/kg body weight per day for 7 months [1].
• The small advantage of selenomethionine was, however, offset by a higher false-positive rate: of 22 patients who proved not to have pancreatic disease, 13 had abnormal isotope scans compared with only 3 with ultrasound [2].
• Randomized, placebo-controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib [3].
• The efficiency of ultrasound in the diagnosis of pancreatic disease was compared prospectively with that of selenomethionine isotope scanning in 46 patients presenting with abdominal pain or weight-loss or with jaundice [2].
• An expression system has been established for the incorporation of selenomethionine into recombinant proteins produced from plasmids in Escherichia coli [4].

High impact information on Selenomethionine

• The biological significance of Se utilization under suboptimal or adequate methionine intake was also assessed using the glutathione peroxidase assay in the liver of Se-deficient rats given graded levels of Se as either selenite or selenomethionine [5].
• Moreover, selenomethionine (SM), a prostate cancer treatment adjuvant, shows an inhibitory effect on LNCaP cell growth, yet has no effect on the AR/PSA pathway [6].
• We show that selenium in the form of selenomethionine (SeMet) can activate the p53 tumor suppressor protein by a redox mechanism that requires the redox factor Ref1 [7].
• Selenomethionine regulation of p53 by a ref1-dependent redox mechanism [7].
• Elevated levels of antioxidant enzymes and apoptosis were inhibited by the nitric oxide synthase inhibitor, S-isopropylisothiourea, and the peroxynitrite scavenger, selenomethionine [8].

Chemical compound and disease context of Selenomethionine

• Uptake studies monitored using L-[75Se]methionine indicated that L-selenomethionine was incorporated into the protein synthetic pathway of Pseudomonas bacteria in a manner analogous to L-methionine [9].
• Here we report the crystal structure of selenomethionine-labelled Escherichia coli DXR in a ternary complex with NADPH and fosmidomycin at 2.2 A resolution [10].
• Recombinant 1,5-anhydro-d-fructose reductase (AFR) from Sinorhizobium morelense S-30.7.5 was crystallized in complex with the cofactor NADP(H) and its structure determined to 2.2 A resolution using selenomethionine SAD (refined R(work) and R(free) factors of 18.9 and 25.0%, respectively) [11].
• To explore the possibility of a small molecule inhibitor of the enzyme functioning as a non-cell wall antibiotic, the structure of HMG-CoA synthase from Enterococcus faecalis (MVAS) was determined by selenomethionine MAD phasing to 2.4 A and the enzyme complexed with its second substrate, acetoacetyl-CoA, to 1.9 A [12].
• The native and the selenomethionine-substituted forms of the phenylalanine-regulated isozyme [DAHPS(Phe)] from Escherichia coli were crystallized in complex with PEP and a metal cofactor, Mn(2+), but the crystals displayed disorder in their unit cells, preventing satisfactory refinement [13].

Biological context of Selenomethionine

• Although treatment of cells with either selenomethionine or trifluoromethionine also reduced the rate of total RNA synthesis, each of these analogs had other effects that presumably prohibited completion of the cell cycle [14].
• Methioninase cancer gene therapy with selenomethionine as suicide prodrug substrate [15].
• We show a possible mechanism for the inducible DNA repair response, in which enhanced repair complex formation was observed in selenomethionine-treated cells [16].
• No significant changes in the pharmacokinetics of CPT-11, SN-38, or SN-38G were identified; however, the coadministration of selenomethionine significantly reduced the irinotecan biliary index, which has been associated with gastrointestinal toxicity [17].
• An essential role of s-adenosyl-L-methionine:L-methionine s-methyltransferase in selenium volatilization by plants. Methylation of selenomethionine to selenium-methyl-L-selenium- methionine, the precursor of volatile selenium [18].

Anatomical context of Selenomethionine

• GPx, like selenomethionine, protected against protein 3-nitrotyrosine formation in human fibroblast lysates, shown in Western blots [19].
• Glial cells contained seven 75Se(2+)-labeled proteins ranging in size from 12 to 62 kDa, none of which corresponded to the type II substrate binding subunit. these data show that, unlike the type I enzyme, the type II enzyme does not contain a selenocysteine or selenomethionine, further emphasizing the differences between these two isozymes [20].
• Accessible tissues such as red blood cells were highly labeled (20-25%) in the subjects receiving selenomethionine [21].
• Upon incubation of J-774 A.1 macrophages with selenomethionine (10 ng/ml) for 1 week, cellular GSH content and GPx activity were increased by about twofold compared to control cells, and this effect was associated with a 30% reduction in cell-mediated oxidation of LDL [22].
• Infants fed human milk from women receiving 0 or 200 micrograms supplemental selenium as selenomethionine or selenium-enriched yeast had plasma selenium that paralleled changes in their selenium intake [23].

Associations of Selenomethionine with other chemical compounds

• Beginning 7 days after 7,12-dimethylbenz(a)anthracene treatment, rats were assigned randomly to the control group or to one of two selenium treatment groups receiving either 3.4 ppm of selenium as sodium selenite or 3.4 ppm as selenomethionine in their drinking water [24].
• A randomized, double-blinded, placebo-controlled 2 x 2 factorial chemoprevention trial was conducted in Linxian, China to assess the effects of selenomethionine and celecoxib on the natural history of esophageal squamous dysplasia [25].
• The formation of nitrite rather than nitrate from peroxynitrite was enhanced by GPx or by selenomethionine [19].
• Plasma was sampled before supplementation and at 4-wk intervals during supplementation and was assayed for the 2 plasma selenoproteins, glutathione peroxidase and selenoprotein P. RESULTS: Full expression of glutathione peroxidase was achieved with 37 mug Se/d as selenomethionine and with 66 mug/d as selenite [26].
• In the present study, we evaluated three different selenium compounds; selenite, selenocystamine, and selenomethionine to determine the relative importance of the prooxidative effects of these compounds with regard to their ability to induce apoptosis [27].

Gene context of Selenomethionine

• The crystal structure of Rv1347c was determined by multiwavelength anomalous diffraction phasing from selenomethionine-substituted protein and refined at 2.2 angstrom resolution (r = 0.227, R(free) = 0.257) [28].
• On the basis of RT-PCR analysis, SM and p-XSC increased p53 gene expression by 2-fold in AR cells but not in AI cells and only SM enhanced epidermal growth factor receptor in AR cells [29].
• Selenomethionine induces sustained ERK phosphorylation leading to cell-cycle arrest in human colon cancer cells [30].
• Both p-XSC and p-XMS reduced cell number and total protein concentration compared to control-treated AR and AI cells, while SM and MSC exhibited no effect on growth of AR and AI cells [29].
• The technique of multiple-wavelength anomalous dispersion (MAD) with the selenomethionine form of IL-1 alpha was utilized in combination with a single mercury derivative to provide the starting phases [31].

Analytical, diagnostic and therapeutic context of Selenomethionine

• Cell-free protein synthesis systems have been developed for large-scale production of protein samples for NMR (stable-isotope labeling) and X-ray crystallography (selenomethionine substitution) [32].
• Phases were obtained from one selenomethionine residue introduced by site-directed mutagenesis [33].
• Instrumental to the structure determination were selenomethionine substitution and the use of argon during purification and crystallization [34].
• The selenoamino acid fraction was isolated by size exclusion LC followed by the separation of selenomethionine and the carboxymethylated selenocysteine by capillary HPLC [35].
• More generally, combining cell-free incorporations of selenomethionine into proteins with FTIR difference spectroscopy provides a useful method for investigating the role of methionines in protein structure and function [36].

References