Evidence for S adenosylmethionine independent catabolism of methionine in the rat

Abstract

The metabolism of the methionine methyl group is thought of principally in terms of the activation of L methionine (Met) to S adenosyl L methionine (SAM) followed by the transfer of the methyl group to numerous acceptor molecules. Young rats adapted to a high Met diet convert up to 45% of the methyl carbon from ingested Met to respired CO2 within 24 hours. It has not been clearly established that this rapid and extensive methyl group oxidation occurs solely by pathways involving the activation of Met to SAM followed by the transfer of the methyl group to intermediary metabolites which yield CO2. Experiments conducted with rats in vivo comparing the metabolism of Met and S methyl L cysteine and in vitro comparing methionine, S methyl L cysteine and SAM indicate that a substantial portion of the oxidative metabolism of the Met methyl group occurs by pathways that are independent of SAM formation. Inclusion of 1.2% or 2.4% of S methyl L cysteine in a diet containing 3% of L Met depressed the conversion of the Met methyl and carboxyl carbons to CO2 by 39% and 28%, and 52% and 33%, respectively, for the two levels of S methyl L cysteine. Inclusion of 1.65% of Met in a diet containing 2.4% of S methyl L cysteine did not affect the conversion of the methyl group of S methylcysteine to CO2, but 3% of Met depressed the conversion of the S methylcysteine methyl group to CO2 to 87% of control values. Greater inhibitions were seen when these substrates were compared in a liver homogenate. In a rat liver homogenate system optimized for the conversion of the methyl group of Met to CO2, the rate of conversion of the methyl group of SAM to CO2 was less than 1% of that of Met even when the concentration of SAM was saturating. Addition of saturating levels of unlabeled SAM to the homogenate system did not effect the rate of conversion of the Met methyl carbon to CO2. Although SAM dependent metabolism of Met, leading to incorporation of the methyl carbon into sarcosine and serine, could be demonstrated in liver homogenates, essentially all of the CO2 produced from the Met methyl group was derived by a pathway or pathways independent of SAM formation. Formaldehyde and formate have been tentatively identified as intermediates in catabolism of the Met methyl group by this (these) pathway(s).