Effect of inhibitors of protein synthesis on rat liver spermidine N-acetyltransferase.
The increase in spermidine N-acetyltransferase activity in rat liver produced by carbon tetrachloride was completely prevented by simultaneous treatment with inhibitors of protein and nucleic acid synthesis suggesting that the increase results from the synthesis of new protein rather than the release of the enzyme from a cryptic inactive form. Treatment with cycloheximide 2 h after carbon tetrachloride also completely blocked the rise in spermidine N-acetyltransferase seen 4 h later. Such treatment completely prevented the fall in spermidine and rise in putrescine in the liver 6 h after carbon tetrachloride confirming the importance of the induction of spermidine N-acetyltransferase in the conversion of spermidine into putrescine. When cycloheximide was administered to rats in which spermidine N-acetyltransferase activity had been stimulated by prior treatment with carbon tetrachloride or thioacetamide, the activity was lost rapidly showing that the enzyme protein has a rapid rate of turnover. The half-life for the enzyme in thioacetamide-treated rats was 40 min, whereas the half-life for ornithine decarboxylase (which is well known to turn over very rapidly) was 27 min. In carbon tetrachloride-treated rats the rate or protein degradation was reduced and the half-life of spermidine N-acetyltransferase was 155 min and that for ornithine decarboxylase was 65 min. It appears that three of the enzymes involved in the synthesis and interconversion of putrescine and spermidine namely, ornithine decarboxylase, S-adenosylmethionine decarboxylase and spermidine N-acetyltransferase have rapid rates of turnover and that polyamine levels are regulated by changes in the amount of these enzymes.
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000201:enzymology*; D008954:Models, Biological; D009955:Ornithine Decarboxylase / Q000378:metabolism; D014176:Protein Biosynthesis; D011700:Putrescine / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D013095:Spermidine / Q000378:metabolism; D013853:Thioacetamide / Q000494:pharmacology; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D002251:Carbon Tetrachloride; D003513:Cycloheximide; D009955:Ornithine Decarboxylase; D011700:Putrescine; D012313:RNA; D013095:Spermidine; D013853:Thioacetamide; D000099228:Diamine N-Acetyltransferase