Figure 1.

Polyamines Biosynthesis and Catabolic Pathway. Polyamine biosynthesis begins with arginine, where arginase (ARG) converts arginine to ornithine. Next, ornithine decarboxylase (ODC) converts ornithine to putrescine. S-adenosylmethionine decarboxylase (SamDC) then catalyzes the decarboxylation of S-adenosylmethionine. Next, spermidine synthase (SpdS) then transfers the aminopropyl moiety from the decarboxylated S-adenosylmethionine to putrescine, converting it into spermidine. Finally, spermine synthase (SpmS) catalyzes a similar aminopropyl transfer activity from the decarboxylated S-adenosylmethionine to convert spermidine to spermine. Polyamine catabolism is catalyzed by spermine/spermidine N1-acetyltransferase (SSAT) and N1-acetylpolyamine oxidase (PAO). SSAT can acetylate spermine and spermidine to N-acetylspermine and N-acetylspermidine, respectively. These acetylated products can be cleaved by PAO into spermidine and putrescine along with a generation of H₂O₂. Spermine can also be oxidized to spermidine by the enzyme spermine oxidase (SMO). For studying the polyamines pathway, two commonly used drugs include difluoromethylornithine (DFMO) which irreversibly inhibits ODC, and N1,N11-diethylnorspermine (DENspm) which activates SSAT.