Toxicity of polyamines and their metabolic products

Polyamines are ubiquitous and essential components of mammalian cells. They have multiple functions including critical roles in nucleic acid and protein synthesis, gene expression, protein function, protection from oxidative damage, the regulation of ion channels, and maintenance of the structure of cellular macromolecules. It is essential to maintain a correct level of polyamines, and this amount is tightly regulated at the levels of transport, synthesis, and degradation. Catabolic pathways generate reactive aldehydes including acrolein and hydrogen peroxide via a number of oxidases. These metabolites, particularly those from spermine, can cause significant toxicity with damage to proteins, DNA, and other cellular components. Their production can be increased as a result of infection or cell damage that releases free polyamines and activates the oxidative catabolic pathways. Since polyamines also have an important physiological role in protection from oxidative damage, the reduction in polyamine content may exacerbate the toxic potential of these agents. Increases in polyamine catabolism have been implicated in the development of diseases including stroke, other neurological diseases, renal failure, liver disease, and cancer. These results provide new opportunities for the early diagnosis, prevention, and treatment of disease.