Chemical structures and the polyamine pathway.

(A) Chemical structure of curcumin (diferuloylmethane). (B) Chemical structures of the natural polyamines spermine, spermidine, and putrescine, the polyamine analogue bis(ethyl)norspermine (BENSpm), and the ODC inhibitor difluoromethylornithine (DFMO). (C) The mammalian polyamine pathway: ornithine decarboxylase (ODC) converts ornithine into putrescine, which acquires sequential aminopropyl groups to form spermidine followed by spermine. The aminopropyl group is derived from decarboxylated S-adenosylmethionine (dcSAM), and its addition onto putrescine or spermidine is mediated by spermidine and spermine synthases (SRM and SMS, respectively). Two routes exist for spermine catabolism: (1) it can be oxidized by spermine oxidase (SMOX) to produce spermidine, which is accompanied by H2O2 and aldehyde generation, or (2) it can undergo acetylation by spermidine/spermine N1-acetyltransferase (SSAT). Acetylated spermine is either exported from the cell or oxidized back to spermidine by peroxisomal N1-acetylpolyamine oxidase (PAOX). Spermidine also undergoes this 2-step acetylation/oxidation back to putrescine via an N1-acetylspermidine intermediate.