Spermidine/spermine-N¹-acetyltransferase (SSAT) regulates cellular polyamine content. Since polyamines play critical roles in normal and neoplastic growth and in ion channel regulation, SSAT is a key enzyme in these processes. SSAT is very highly regulated. Its content is adjusted in response to alterations in polyamine content to maintain polyamine homeostasis. Certain polyamine analogs can mimic the induction of SSAT and cause a loss of normal polyamines. This may have utility in cancer chemotherapy. SSAT activity is also induced via a variety of other stimuli including toxins, hormones, cytokines, natural products, and stress pathways and by ischemia-reperfusion injury. Transgenic manipulation of SSAT activity has revealed that, in addition to effects mediated directly via alterations in polyamine catabolism, SSAT activity links polyamine metabolism to lipid and carbohydrate metabolism by means of alterations in the content of acetyl-CoA and ATP. A variety of other effects of increased SSAT activity include death of pancreatic cells, blockage of regenerative tissue growth, behavioral changes, keratosis follicularis spinulosa decalvans and hair loss. These are very likely due to changes in polyamine and putrescine levels, although increased oxidative stress via the oxidation of acetylated polyamines may also contribute. Recently, it has been found that the SSAT protein and/or a related protein thialysine acetyltransferase interact with a number of other important proteins including the HIF-1α subunit, the p65 subunit of NF-B and α9β1 integrin and alters the function of these proteins. It is not yet clear whether this functional alteration involves protein acetylation, local polyamine concentration changes or other effects.

Key words: Polyamines, Spermine, Spermidine, Acetyl CoA