Cysteinesulfinate Metabolism

L-Cysteinesulfinate, a quantitatively important catabolite of L-cysteine, is a substrate of both cysteinesulfinate decarboxylase and glutamate-oxaloacetate transaminase. The former enzyme initiates a pathway leading to taurine; the latter enzyme forms /3-sulfinylpyruvate, which spontaneously decomposes to pyruvate and SOZ. In the present studies, the in uiuo partitioning of cysteinesulfinate between these two pathways was evaluated by administering to mice ~-[l-‘~Cl cysteinesulfinate, which is metabolized to 14C02 by both pathways, or L-[3-‘4C]cysteinesulfinate, which is converted to 14C02 only if taurine is not formed. Within 6 h, respiratory 14C02 accounted for 90% of the [l-‘“Cl cysteinesulfinate injected, whereas only 18% of administered [3-‘4C]cysteinesulfinate was recovered as 14COz. When the data are corrected for differences in the formation of 14C02 from [l-‘“Cland [3-14C]pyruvate and for a small formation of 14C02 from radiolabeled hypotaurine, it is concluded that -85% of administered cysteinesulfinate is decarboxylated to hypotaurine, whereas -15% is transaminated. Of the hypotaurine formed, -90% is oxidized to taurine. P-Methylene-DLaspartate, an irreversible inhibitor of glutamate-oxaloacetate transaminase (Cooper, A. J. L., Fitzpatrick, S. M., Kaufman, C., and Dowd, P. (1982) J. Am. Chem. Sot. 104, 332-334) was given to mice with the expectation that conversion of cysteinesulfinate to hypotaurine would be increased. Surprisingly, the extent of cysteinesulfinate transamination increased about 3-fold. Additional studies indicate that P-methyleneaspartate is a potent, irreversible inhibitor of purified rat liver cysteinesulfinate decarboxylase and that inactivation of the decarboxylase predominates over inactivation of the transaminase in ho. Highly purified cysteinesulfinate decarboxylase is also shown to decarboxylate L-aspartate to p-alanine and, very slowly, glutamate to y-aminobutyrate. The enzyme is not active toward a-methylcysteinesulfinate or a-methylaspartate; a-methyl-oL-[l-‘4C]cysteinesulfinate is not metabolized by the mouse.