THE INABILITY OF THE RAT TO UTILIZE THE METHYL GROUPS OF METHIONINE SULFONE AND OXIDIZED CASEIN FOR METHYLATION OF HOMOCYSTINE

Abstract

Methionine sulfone has been found incapable of substituting for methionine in the growth of the rat (1).When casein is oxidized by hydrogen peroxide, the resulting oxidized casein (2) cannot support the growth of the rats unless the tryptophan and methionine oxidized in the process are replaced (3).This fact, together with chemical evidence (2), indicates that in the modified protein molecule methionine has been converted to the sulfone, rather than to the sulfoxide which will support growth (4).By paper chromatography of hydrolysates, Dent (5) recently confirmed the absence of methionine sulfoxide and the presence of the sulfone in oxidized casein.The rat experiments (1,3), as well as the frequent use of oxidized casein in bacteriological assay work, indicate the absence of metabolic conversion of methionine sulfone, either as free amino acid or in protein linkage, to methionine.However, the possibility remains that the methyl group of the sulfone may be available for transmethylation.A recent paper by Valyi-Nagy (6) gives evidence for an intermediary rBle of the sulfoxide in the demethylation of methionine.This author also implicates sulfone formation as an intermediary step in the process, although without experimental support.An experiment mentioned by us earlier (3) showed pronounced growth of rats when a choline-free diet containing 15 per cent oxidized casein was supplemented with 0.36 per cent homocystine, suggesting the conclusion, at that time, that transmethylation may occur.It was subsequently found that under the conditions of this laboratory homocystine will induce growth without the benefit of methyl donors in the diet (7).In the light of this finding the conclusion that the methyl of methionine sulfone is available for methylation of homocystine became questionable.Further study indicated that the ability of our rats to grow in the absence of known methyl donors is related to preexperimental nutritional conditions which evidently result in the storage of a factor or factors involved in methylation and possibly a synthesis of such factors by intestinal bacteria (8, 9).It became possible to abolish the homocystine-induced 163