Cysteine conjugate of methazolamide is metabolized by beta-lyase

Bovine kidney and liver homogenates degraded a cysteine conjugate of methazolamide, S-(5-acetylimino-4-methyl-Delta2-1,3,4-thiadiazolin-2-yl)cysteine. We isolated the degradation product following incubation with kidney homogenate by high-performance liquid chromatography on reversed-phase columns. The chemical structure was confirmed by proton and carbon-13 nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR, respectively), and elemental analysis by high-resolution mass spectrometry to be N-(3-methyl-5-mercapto-Delta4-1,3,4-thiadiazol-2-yl)acetamide, a thiol compound. The reaction is thought to be catalyzed by a pyridoxal-dependent enzyme(s) as indicated by an inhibition study using aminooxyacetic acid. Possible involvement of the thiol compound in the development of an adverse effect is discussed.