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Evidence for S-adenosylmethionine Independent Catabolism of Methionine in the Rat^1,2,

Departments of Nutritional Sciences and Meat and Animal Science, University of Wisconsin, Madison, Wisconsin 53706

Experiments conducted with rats in vivo comparing the metabolism of methionine and S-methyl-L-cysteine and in vitro comparing methionine, S-methyl-L-cysteine and S-adenosyl-L-methionine indicate that a substantial portion of the oxidative metabolism of the methionine methyl group occurs by pathways that are independent of S-adenosylmethionine formation. Inclusion of 1.2% or 2.4% of S-methyl-L-cysteine in a diet containing 3% of L-methionine depressed the conversion of the methionine 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 methionine 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 methionine 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 methionine to CO₂, the rate of conversion of the methyl group of S-adenosyl-L-methionine to CO₂ was less than 1% of that of methionine even when the concentration of S-adenosylmethionine was saturating. Addition of saturating levels of unlabeled S-adenosylmethionine to the homogenate system did not effect the rate of conversion of the methionine methyl carbon to CO₂. Although S-adenosylmethionine-dependent metabolism of methionine, 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 methionine methyl group was derived by a pathway or pathways independent of S-adenosylmethionine formation. Formaldehyde and formate have been tentatively identified as intermediates in catabolism of the methionine methyl group by this (these) pathway(s).

KEY WORDS: • methyl groups • methionine • S-methylcysteine • S-adenosylmethionine

¹ Research supported by funds from the College of Agricultural and Life Sciences. University of Wisconsin, the Graduate School, University of Wisconsin and by Public Health Service Research Grant #AM 15227.

² Paper No. 675 from the Department of Meat and Animal Science.

³ Present address: Department of Physiology and Biophysics, Colorado State University, Fort Collins, Colorado 80521.

Manuscript received 29 January 1976.