title: Mammals reduce methionine-S-sulfoxide with MsrA and are unable to reduce methionine-R-sulfoxide, and this function can be restored with a yeast reductase.
abstract: Methionine is an essential amino acid in mammals at the junction of methylation, protein synthesis, and sulfur pathways. However, this amino acid is highly susceptible to oxidation, resulting in a mixture of methionine-S-sulfoxide and methionine-R-sulfoxide. Whether methionine is quantitatively regenerated from these compounds is unknown. Here we report that SK-Hep1 hepatocytes grew on methionine-S-sulfoxide and consumed this compound by import and methionine-S-sulfoxide reductase (MsrA)-dependent reduction, but methionine-R-sulfoxide reductases were not involved in this process, and methionine-R-sulfoxide could not be used by the cells. However, SK-Hep1 cells expressing a yeast free methionine-R-sulfoxide reductase proliferated in the presence of either sulfoxide, reduced them, and showed increased resistance to oxidative stress. Only methionine-R-sulfoxide was detected in the plasma of wild type mice, but both sulfoxides were in the plasma of MsrA knock-out mice. These results show that mammals can support methionine metabolism by reduction of methionine-S-sulfoxide, that this process is dependent on MsrA, that mammals are inherently deficient in the reduction of methionine-R-sulfoxide, and that expression of yeast free methionine-R-sulfoxide reductase can fully compensate for this deficiency.
authors.affiliation: Redox Biology Center, University of Nebraska, Lincoln, Nebraska 68588-0664, USA.
authors.forename: Byung Cheon
authors.initials: BC
authors.lastname: Lee
authors.forename: Dung Tien
authors.initials: DT
authors.lastname: Le
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008322:Mammals; D008715:Methionine / Q000031:analogs & derivatives* / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010088:Oxidoreductases / Q000378:metabolism*; D051140:Selenoproteins / Q000737:chemistry; D013997:Time Factors; D014162:Transfection; D015003:Yeasts / Q000201:enzymology*
chemical_list: D051140:Selenoproteins; D008715:Methionine; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; C013111:methionine sulfoxide