Enzymatic Reactions of Methionine Sulfoximine CONVERSION TO THE CORRESPONDING a-IMINO AND a-KETO ACIDS AND TO a-KETOBUTYRATE AND METHANE SULFINIMIDE*

L-Methionine sulfoximine is a substrate of L-amino acid oxidase (Crotalus adamanteus), glutamine transaminase, and y-cystathionase. In the reaction catalyzed by L-amino acid oxidase, methionine sulfoximine is converted to oc-imino-y-methylsulfoximinylbutyrate, which undergoes rapid y elimination yielding methane sulfinimide and 2-imino-3-butenoic acid. Methane sulfinimide is converted to methane sulfonamide, methane sulfinic acid, and methane sulfonic acid; 2-imino&butenoic acid is hydrolyzed to vinylglyoxylate, which polymerizes to an insoluble product. When the reaction is carried out in the presence of semicarbazide, the imine formed initially is quantitatively trapped as a-keto-y-methylsulfoximinylbutyrate semicarbazone, from which the free cY-keto acid may be obtained. When the reaction is carried out in the presence of a mercaptan (RSH), a y exchange reaction occurs leading to formation of a new ol-keto acid substituted in the y position by an SR-group; thus, oc-keto-y-(P-hydroxyethiol)butyric acid (S-(hydroxyethyl)-2-keto-4-mercaptobutyric acid) was obtained when L-methionine sulfoximine was oxidized in the presence of 2-mercaptoethanol, and enzymatic transamination of this cy-keto acid with L-glutamine gave the new amino acid, cw-hydroxyethionine. The reaction of L-methionine sulfoximine with y-cystathionase yields 1 mol each of a-ketobutyrate and methane sulfinimide; the latter is hydrolyzed almost exclusively to methane sulfinic acid. Transamination of L-methionine sulfoximine yields the corresponding cu-keto acid (a-keto-y-methylsulfoximinylbutyrate), which is stable. Some of these reactions may occur in vivo, and thus contribute to the toxicity of Lmethionine sulfoximine.