Selenium metabolites

Hasunuma, R., T. Ogawa, Y. Fujise, and Y. Kawanashi. 1993. Analysis of selenium metabolites in urine samples of minke whales (Balaenoptera acutorostrata) using ion exchange chromatography. Comp. Biochem. Physiol. 104C 87-89. 

Figure 2 Selenium metabolites and critical metabolic intermediates in selenoprotein synthesis. Two-dimensional structures of each molecule are shown with common name below.

Nakamuro, K., Nakanishi, K., Okuno, T., Hasegawa, T., and Sayato, Y. 1997. Comparison of methylated selenium metabolites in rats after oral administration of various selenium compounds. Jpn. J. Toxicol. Environ. Health 43, 182-189. 

B. Gammelgaard, K. E. Madsen, J. Bjerrum, L. Bendahl, O. Jons, J. Olsen, U. Sidenius, Separation, purification and identification of the major selenium metabolite from human urine by multidimensional HPLC-ICP-MS and APCI-MS, J. Anal. Atom. Spectrom., 18 (2003), 65-70. 

Lanfear, J., Fleming, J., Wu, L., VVeb.ster, G., and Harrison, P R. (1994). The selenium metabolite selenodiglutathionc induces p.53 and apoptosis Relevance to the chemopre vention effects of selenium CitTCinogetiessi 15,1387-1392. 

These 16 compounds identified in urine mostly by HPLC/ICPMS include the compound 102 plus 15 other selenium metabolites (Table 18). For many of these, the assignments have been made on very little evidence and require confirmation before the compounds can be accepted as typical urine metabolites [216, 217]. Some, such as methylselenol, have already been retracted by their discoverers. Selenosugar 95 is now firmly established as a major urinary metabolite when selenium is administered, and it is also a constituent of natural urine. There have also been reports of selenosugar 94 and selenosugar 96 as minor constituents. Selenite appears to be a common minor metabolite in normal urine. 

Selenosugar(96) 4 Yes firmly established as a major selenium metabolite after supplementation with selenite or selenized yeast also data showing it is present in... 

Ongoing investigations into selenium metabolism include state-of-the-art methods such as HPLC/ICPMS in combination with MS/MS. Data on the profile of selenium metabolites will elucidate the element s essential and toxic roles and relate individual Se species with observed health effects. 

Se NMR spectroscopy has been considered a suitable method for tracing selenium metabolites or the fate of organoselenides in a hydrobromic acid -bromine digestion system. In particular, selena analogues of the amino acids... 

The major selenium metabolite from human urine identified as Se-sugar (methylseleno-A-acetylselenohexosamine)... 

Ogra, Y, Ishiwata, K., Takayama, H., Aimi, N., Suzuki, K. T. Identification of a novel selenium metabolite, 5e-methyl-iV-acetylselenohexosamine, in rat urine by high-performance liquid... 

In vitro studies of human plasma and whole blood incubated with sodium selenite have indicated that selenite is accumulated in erythrocytes by an active transport mechanism (Lee et al. 1969). Several studies indicate that the selenite is chemically altered in the erythrocyte and then transported back into the plasma, where the selenium metabolite binds to plasma proteins (Burk 1974 Hirooka and Galambos 1966a Lee et al. 1969). 

In rats, the trimethylselenonium ion has been identified as the predominant urinary metabolite following intraperitoneal administration of sodium selenite (Byard and Baumann 1967), sodium selenate, selenomethionine, selenocystine, or methylselenocysteine, or following ingestion of seleniferous wheat (Palmer et al. 1970). A total of 30.8% of the urinary selenium was in the form of trimethylselenonium after administration of 15 ppm selenium in wheat. Another major selenium metabolite that appeared in the urine more slowly than the trimethylselenonium ion was identified chromatographically, but the chemical structure of that metabolite was not defined (Palmer et al. 1970). 

The arrow with an asterisk indicates the site of the oral Se tracer. Arrows between compartments represent pathways of fractional transport. Compartments depicted as rectangles represent delays. G1, G2, G3, three gut compartments, probably small intestine ENT, enterocytes (intestinal cells) HPL, compartment in hepatopancreatic subsystems or lymphatic system L/P, liver and pancreas LI, large intestine T1, T2, T3, T4, peripheral tissues, e.g., skeletal muscle, bone, kidney. Feces and urine along the gastrointestinal tract, enterohepatic recirculation, four kinetically distinct plasma pools, P1-P4, a subsystem consisting of the liver and pancreas, two tissue subsystems that are slowly turning-over, and a pathway for reutilization of selenium metabolites from peripheral tissues. The bold lines indicate the major modifications to the Selenite Model (Figure 3-8). 

The metabolism of selenium is now fairly well understood. To become incorporated into selenium-specific proteins (e.g., glutathione peroxidase, thioredoxin reductase, iodothyronine 5 -deiodinase) through a cotranslational mechanism requires that selenium be in the form of selenide (Sunde 1990). All forms of selenium can be transformed to selenide, although the rates of transformation vary. For example, selenate is not converted to selenide as readily as selenite. The formation of selenide from selenocysteine requires a specific enzyme, selenocysteine (3-lyase, which catalyzes the decomposition of selenocysteine to alanine and hydrogen selenide. Excess selenium is methylated and exhaled or excreted in the urine in both humans and animals. Further research is required to determine which selenium metabolites or intermediates lead to toxicity. 

Byard JL, Baumann CA. 1967. Selenium metabolites in the urine of rats given a subacute dose of selenite [Abstract], Fed F roc 26 479. 

Hasunuma R, Tsuda M, Ogawa T, et al. 1993. Selenium metabolite levels in human urine after dosing selenium in different chemical forms. Bull Environ Contam Toxicol 51 756-763. 

Ip C, Thompson HJ, Zhu Z, et al. 2000b. In vitro and in vivo studies of methylseleninic acid Evidence that a monomethylated selenium metabolite is critical for cancer chemoprevention. Cancer Res 60 2882-... 

Wu L, Lanfear J, Harrison PR. 1995a. The selenium metabolite selenodiglutathione induces cell death by a mechanism distinct from H202 toxicity. Carcinogenesis 16(7) 1579-1584. 

The work of Kuehnelt et provided the first quantitative data on excretion rate and relative quantities of the various selenium metabolites, and showed that selenosugar F13-1 was by far the major metabolite (70%) with smaller quantities of selenosugars F13-2 and F13-3. Differences in excretion rate were also noted depending on the form of selenium ingested, but the metabolic pattern of compounds remained the same. These data support an accepted metabolic pathway for selenium that describes various selenium sources converting to selenide, which is then transformed into selenocysteine and incorporated into selenoproteins. ... 

Monovalent gold salts impacted metabolism of seleifium, copper, and zinc. Intravenous Au" " may adversely affect the availability of seleifium for synthesis of selenoenzymes. Rats given gold sodium thiomalate iv at 25.0 or 50.0 xmol/kg BW had sigifificantly altered seleifium deposition, as measured by radioselenium-75. These effects included the almost complete cessation of Se exhalation as dimethyl sulfide and the accumulation of Se in blood plasma. Direct chemical reaction with nucleophilic selenium metabolites in the body may underlie these alterations. Auranofin inhibited selenium-glutathione peroxidase in bovine erythrocytes this enzyme... 

Electrospray MS that allows a precise ( lDa) determination of molecular mass is an invaluable tool for the identification and a prerequisite for further characterization of compounds in speciation analysis. ESTMS has been applied mostly to commercial standards or synthetic preparations. Pneumatically assisted ESTMS is used to identify Se-adenosylhomocysteine in an extract of selenized yeast. Selenium in garlic has been speciated by parallel ICP-MS and electrospray tandem MS. A novel selenium metabolite in rat mine, the selenosugar di-asteriomer Se-methyl-N-acetylhexosamine, has been identified by this method. It should be emphasized that when authentic standards are not available the use of tandem MS is vital to confirm selenium speciation indicated by means of hyphenated seleni-mn-specific detection. 

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