Polyamine catabolism and disease

In addition to polyamine homoeostasis, it has become increasingly clear that polyamine catabolism call play a dominant role in drug response, apoptosis and the response 10 stressful, and contribute to the aetiology of several pathological states, including cancer. The highly inducible enzymes SSAT (spermidine/spermine N-1-acetyltransferase) and SMO (spermine oxidase) and the generally Constitutively expressed APAO (N-1-acetylpolyamine oxidase) appear to play critical roles in many normal and disease processes. The dysregulation of polyamine catabolism frequently accompanies several disease states and suggests that such dysregulation may both provide useful insight into disease mechanism and provide unique druggable targets that call be exploited for therapeutic benefit. Each of these enzymes has the potential to after polyamine homoeostasis in response to multiple cell signals and the two oxidases produce the reactive oxygen species H2O2 and aldehydes, each with the potential to produce pathological states. The activity of SSAT provides Substrates for APAO or substrates for the polyamine exporter, thus reducing the intracellular polyamine concentration, the net effect of which depends oil the magnitude and rate of any increase in SSAT. SSAT may also influence cellular metabolism via interaction with other proteins and by perturbing the content of acetyl-CoA and ATP. The goal of the present review is to cover those aspects of polyamine catabolism that have an impact on disease aetiology or treatment And to provide a solid background in this ever more exciting aspect of polyamine biology.