Authors: Tuomo A Keinänen Mervi T Hyvönen Leena Alhonen Jouko Vepsäläinen Alex R Khomutov
Publish Date: 2013/09/11
Volume: 46, Issue: 3, Pages: 605-620
Abstract
Polyamine metabolism is intimately linked to the physiological state of the cell Low polyamines levels promote growth cessation while increased concentrations are often associated with rapid proliferation or cancer Delicately balanced biosynthesis catabolism uptake and excretion are very important for maintaining the intracellular polyamine homeostasis and deregulated polyamine metabolism is associated with imbalanced metabolic red/ox state Although many cellular targets of polyamines have been described the precise molecular mechanisms in these interactions are largely unknown Polyamines are readily interconvertible which complicate studies on the functions of the individual polyamines Thus nonmetabolizable polyamine analogues like carbonmethylated analogues are needed to circumvent that problem This review focuses on methylated putrescine spermidine and spermine analogues in which at least one hydrogen atom attached to polyamine carbon backbone has been replaced by a methyl group These analogues allow the regulation of both metabolic and catabolic fates of the parent molecule Substituting the natural polyamines with methylated analogues offers means to study either the functions of an individual polyamine or the effects of altered polyamine metabolism on cell physiology In general gemdimethylated analogues are considered to be nonmetabolizable by polyamine catabolizing enzymes spermidine/spermineN 1acetyltransferase and acetylpolyamine oxidase and they support shortterm cellular proliferation in many experimental models Monomethylation renders the analogues chiral offering some advantage over gemdimethylated analogues in the specific regulation of polyamine metabolism Thus methylated polyamine analogues are practical tools to meet existing biological challenges in solving the physiological functions of polyamines
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