Methioninase and selenomethionine but not Se-methylselenocysteine generate methylselenol and superoxide in an in vitro chemiluminescent assay: Implications for the nutritional carcinostatic activity of selenoamino acids

Julian E. Spallholz, Vince P. Palace, Ted W. Reid

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

Methylselenol from selenium metabolism is postulated to be and most experimental evidence now indicates that it is the selenium metabolite responsible for the dietary chemoprevention of cancers. Using the recombinant enzyme methioninase, methylselenol-generating chemiluminesence by superoxide (O2.-) is shown to be catalytically produced from L-selenomethionine and D,L-selenoethionine, but not from methionine or L-Se-methylselenocysteine (SeMC). Methylselenol enzymaticaly generated by methioninase activity from the substrate selenomethionine arises from an initial putative selenium radical as measured by chemiluminesence in the absence of glutathione (GSH). In the presence of GSH, superoxide was generated as measured by chemiluminesence and superoxide dismutase inhibition of chemiluminescence. Ascorbic acid also quenched the chemiluminesence from the activity of methioninase with selenomethionine. Methylselenol and other redox cycling selenium compounds are almost assuredly accountable for inducing cell-cycle arrest and apoptosis in cancer cells in vitro and in vivo. Methylselenol generated from selenomethionine by methioninase is catalytic alone in oxidizing thiols, i.e. GSH, generating superoxide and inducing oxidative stress in direct proportion to its concentration. Se- methylselenocysteine in vivo is very likely carcinostatic in like manner to selenomethionine by generating methylselenol from other enzymatic activity, i.e. beta-lyase or amino acid oxidases.

Original languageEnglish
Pages (from-to)547-554
Number of pages8
JournalBiochemical Pharmacology
Volume67
Issue number3
DOIs
StatePublished - Feb 1 2004

Keywords

  • Apoptosis
  • Cancer
  • Methylselenol
  • Se-methylselenocysteine
  • Selenium
  • Selenomethionine
  • Superoxide

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