Developmental aspects of polyamine interconversion in rat brain

Abstract

In the mammalian organism putrescine is formed by two reactions: (a) decarboxylation of ornithine and (b) degradation of spermidine via the so-called interconversion pathway. The latter comprises N1-acetylation of spermidine by a cytosolic acetyltransferase. and oxidative splitting of N1-acetylspermidine to putrescine by polyamine oxidase (PAO). It has previously been shown that specific inhibition of PAO causes a time-dependent accumulation of N1-acetylspermidine in brain, which is a measure of spermidine turnover. Another consequence of PAO inhibition is the decrease of brain putrescine concentration, proportional to its normal formation from spermidine. This observation allowed us to demonstrate the increasing significance of polyamine interconversion with brain maturation. The results support our hypothesis that the mechanisms which regulate cellular polyamine concentrations change during normal brain maturation from a system in which l-ornithine decarboxylase is dominating to a more sophisticated system in which both synthetic and catabolic processes become equally important regulatory factors.In contrast with current views, the activity of S-adenosylmethionine decarboxylase rather than that of ornithine decarboxylase limits the rate of polyamine biosynthesis during early brain development. In the mature brain the total amount of putrescine, which is formed both by decarboxylation of ornithine and by degradation of spermidine, limits the rate of spermidine formation. Changes of the regulatory system analogous to those described in this work are presumably not exclusive for brain, but rather characteristic for a variety of differentiating cells.