Figure 1.

Polyamine Metabolism and Transport. Ornithine is converted to putrescine via ornithine decarboxylase (ODC). Methionine is converted to S-adenosylmethionine (SAM) via methionine adenosyltransferase (MAT) and SAM is converted to decarboxylated S-adenosylmethionine (dc-SAM) via the action of S-adenosylmethionine decarboxylase (SAMDC). Putrescine is converted to spermidine via spermidine synthase (SRM) and an aminopropyl fragment derived from dc-SAM. Similarly, spermidine is converted to spermine via spermine synthase (SMS) and dc-SAM. Back conversion can occur via N-acetylation using spermidine/spermine N¹-acetyltransferase (SSAT) to form N¹-acetyl derivatives, which can be oxidized by acetylpolyamine oxidase (APAO) to generate the respective polyamine. N¹-acetylpolyamines can also be excreted by cells to maintain intracellular polyamine levels and exogenous polyamines can be imported to increase intracellular polyamine pools via the polyamine transport system. Spermine oxidase (SMOX) allows direct conversion of spermine to spermidine. PDAC: pancreatic ductal adenocarcinoma; DFMO: difluoromethylornithine; MCHA: trans-4-methyl-cyclohexylamine; CDAP: N-cyclohexyl-1,3-diaminopropane; PTI: polyamine transport inhibitor.