Selective regulation of S-adenosylmethionine decarboxylase activity by the spermine analogue 6-spermyne.
Polyamine-biosynthesis activity is known to be negatively regulated by intracellular polyamine pools. Accordingly, treatment of cultured L1210 cells with 10 microM-spermine rapidly and significantly lowered ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) activities in a sequential manner. By contrast, treatment for 48 h with 10 microM of the unsaturated spermine analogue 6-spermyne lowered AdoMetDC activity, but not ODC activity. An initial decrease in ODC activity at 2 h was attributed to a transient increase in free intracellular spermidine and spermine brought about through their displacement by the analogue. Thereafter, ODC activity recovered steadily to control values as 6-spermyne pools increased and spermidine and spermine pools decreased owing to analogue suppression of AdoMetDC activity. The apparent ability of 6-spermyne to regulate AdoMetDC, but not ODC, activity suggests an interesting structure-function correlation and demonstrates that the typical co-regulation of these enzyme activities can be dissociated. This, in turn, may reflect the existence of independent regulatory binding sites for the two enzymes.
Porter
C W
CW
Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, NY 14263.
McManis
J
J
Lee
D
D
Bergeron
R J
RJ
D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism*; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D011073:Polyamines / Q000096:biosynthesis; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D011073:Polyamines; C057395:6-spermyne; D013096:Spermine; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase