Properties of spermidine N-acetyltransferase from livers of rats treated with carbon tetrachloride and its role in the conversion of spermidine into putrescine.

A cytosolic spermidine N-acetyltransferase has been partially purified from livers of rats treated with carbon tetrachloride or thioacetamide. This enzyme formed N’-acetylspermidine when incubated with spermidine and acetyl-coA. The enzyme was also able to acetylate spermine, norspermidine, norspermine and, at a much slower rate, 1,3-diaminopropane. Putrescine, cadaverine, homospermidine, and histones were not substrates ( ~ 2 % activity of spermidine) distinguishing this enzyme from a previously described chromatinassociated N-acetyltransferase which acetylates histones and numerous polyamines including putrescine. The enhancement of the N’-acetylspermidine synthase by carbon tetrachloride required both protein and RNA synthesis. Crude liver extracts from carbon tetrachloride-treated rats in which spermidine N-acetyltransferase activity had greatly increased were able to carry out the conversion of spermidine into putrescine in vitro provided that acetyl-coA was added. Oxidation of N‘-acetylspermidine by polyamine oxidase appears likely to be responsible for this reaction. The 40-fold increase in putrescine content of the liver within 6 h of treatment with carbon tetrachloride was not reduced significantly by administration of a-difluoromethylornithine which prevented the rise in ornithine decarboxylase. However, by 12 h the rise in putrescine was substantially reduced by a-dlfluoromethylornithine. These results indicate that the pathway of putrescine production via spermidine acetylation and oxidation was responsible for most of the rise in putrescine up to 6 h after treatment with carbon tetrachloride but that decarboxylation of ornithine was the predominant pathway at later times.