Biosynthesis of Polyamines in Mouse Brain: Effects of Methionine Sulfoximine and Adenosylhomocysteine

Abstract

This study examines the consequences on cerebral polyamine biosynthesis of increases and decreases in cerebral methylation. Increases were elicited by administering the convulsant agent methionine sulfoximine (MSO) and decreases by elevating in vivo the cerebral levels of the methylation inhibitor S -adenosyl-homocysteine. Following the intraventricular (i.vt.) administration of one of the two possible polyamine precursors, [1,4- 14 C]putrescine, the specific radioactivity (sra) of the newly formed [ 14 C]spermidine remained unchanged. Conversely, after i.vt. l-[3,4- 14 C]methionine, the other polyamine precursor, significantly higher sra values for [ 14 C]spermidine and [ 14 C]spermine were recorded in the brains of the MSO-treated animals. [ 14 C] S - adenosylmethionine in the brain of the MSO-treated animals was also more highly labeled following [1- 14 C]-methionine, indicating its accelerated formation relative to controls. We also investigated the effect of the administration of adenosine + homocysteine, a treatment that results in elevated brain adenosylhomocysteine levels, on polyamine biosynthesis from [3,4- 14 C]-methionine. The results of these experiments show both significantly lower sra values for [ 14 C]spermidine and [ 14 C]spermine and significantly higher than control endogenous methionine levels, a clear sign of the existence of a retardation in the conversion of methionine to polyamines under these conditions. In conclusion, the present study demonstrates that while interference with cerebral methylation results in significant alterations of the rate of formation of the methionine moiety of spermidine and spermine, it has no effect on the entry of the putrescine moiety into the two polyamine molecules.