Cysteinesulfinate metabolism. altered partitioning between transamination and decarboxylation following administration of beta-methyleneaspartate.

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 beta-sulfinyl-pyruvate, which spontaneously decomposes to pyruvate and SO2. In the present studies, the in vivo partitioning of cysteinesulfinate between these two pathways was evaluated by administering to mice L-[1-14C]cysteinesulfinate, which is metabolized to 14CO2 by both pathways, or L-[3-14C]cysteinesulfinate, which is converted to 14CO2 only if taurine is not formed. Within 6 h, respiratory 14CO2 accounted for 90% of the [1-14C]cysteinesulfinate injected, whereas only 18% of administered [3-14C]cysteinesulfinate was recovered as 14CO2. When the data are corrected for differences in the formation of 14CO2 from [1-14C]- and [3-14C]pyruvate and for a small formation of 14CO2 from radiolabeled hypotaurine, it is concluded that approximately 85% of administered cysteinesulfinate is decarboxylated to hypotaurine, whereas approximately 15% is transaminated. Of the hypotaurine formed, approximately 90% is oxidized to taurine. beta-Methylene-DL-aspartate, an irreversible inhibitor of glutamate-oxal-oacetate transaminase (Cooper, A.J.L., Fitzpatrick, S. M., Kaufman, C., and Dowd, P. (1982) J. Am. Chem. Soc. 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 beta-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 vivo. Highly purified cysteinesulfinate decarboxylase is also shown to decarboxylate L-aspartate to beta-alanine and, very slowly, glutamate to gamma-aminobutyrate. The enzyme is not active toward alpha-methylcysteinesulfinate or alpha-methylaspartate; alpha-methyl-DL-[1-14C]cysteinesulfinate is not metabolized by the mouse.