Metabolism, cellular actions, and cytotoxicity of selenomethionine in cultured cells.
Selenomethionine metabolism and the biochemical basis for its cytotoxicity were analyzed in cultured human and murine lymphoid cells. The metabolic pathways were also addressed, using purified mammalian enzymes and crude tissue extracts. Selenomethionine was found to be effectively metabolized to S-adenosylmethionine analog, and that analog was further metabolized in transmethylation reactions and in polyamine synthesis, similarly to the corresponding sulphur metabolites of methionine. Selenomethionine did not block these pathways, nor was there a specific block on the synthesis of DNA, RNA, or proteins when added to the culture medium. Selenomethionine showed cytotoxicity at above 40 microM levels. Yet, low selenomethionine levels (10 microM) could replace methionine and support cell growth in the absence of methionine. Selenomethionine toxicity took place concomitantly with changes in S-adenosylmethionine pools. D-form was less cytotoxic than L-form. Methionine concentration modified the cytotoxicity. Together, this indicates that selenomethionine uptake and enzymic metabolism are involved in the cytotoxicity in a yet unknown way.
Kajander
E O
EO
Department of Biochemistry and Biotechnology, University of Kuopio, Finland.
Harvima
R J
RJ
Eloranta
T O
TO
Martikainen
H
H
Kantola
M
M
Kärenlampi
S O
SO
Akerman
K
K
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008223:Lymphoma; D008715:Methionine / Q000378:metabolism*; D008716:Methionine Adenosyltransferase / Q000378:metabolism; D008745:Methylation; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012436:S-Adenosylmethionine / Q000378:metabolism; D012645:Selenomethionine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C069627:adenosylselenomethionine; D012436:S-Adenosylmethionine; D012645:Selenomethionine; D008715:Methionine; D008716:Methionine Adenosyltransferase