Polyamines in living organisms

Abstract

Natural polyamines, putrescine, spermidine and spermine are ubiquitous cell components essential for normal cellular functions and growth. Chemically these compounds are very simple organic aliphatic cations and fully protonated under physiological conditions. There is a strong correlation between proliferation rate of the cells and their polyamine contents. Adjustments of intracellular concentrations of polyamines to physiological requirements are orchestrated by synthesis, polyamine uptake and catabolic reactions. synthesis can in principle be substituted by polyamine uptake from extracellular environment. Over accumulation of polyamines is controlled by release and by a feedback regulation system that involves synthesis of a protein, antizyme that leads to degradation of ornithine decarboxylase and repression of polyamine uptake. The development of specific polyamine biosynthesis inhibitors and structural analogues of polyamines have revealed that maintaining polyamine levels are a prerequisite for animal cell proliferation to occur. The interruption of polyamine biosynthesis or minimizing the uptake of exogenous polyamines via the polyamine transport system offers meaningful targets for treatment of certain hyperproliferative diseases, most notably cancer. The polyamines influence confusingly large number biological processes, yet despite several decades of intensive research work, their exact functions in living organisms remains obscure. In this review, the current state of scientific knowledge regarding polyamines, their functions and their metabolism in mammalian cells is presented.