Cysteine conjugate of methazolamide is metabolized by beta-lyase

Bovine kidney and liver homogenates degraded a cysteine conjugate of methaz olamide, S-(5-acetylimino-4-methyl-Delta (2)-1,3,4-thiadiazolin-2-yl)cystei ne. We isolated the degradation product following incubation with kidney ho mogenate by high-performance liquid chromatography on reversed-phase column s. The chemical structure was confirmed by proton and carbon-13 nuclear mag netic resonance spectroscopy (H-1 NMR and C-13 NMR, respectively), and elem ental analysis by high-resolution mass spectrometry to be N-(3-methyl-5-mer capto-Delta (4)-1,3,4-thiadiazol-2-yl)acetamide, a thiol compound. The reac tion is thought to be catalyzed by a pyridoxal-dependent enzyme(s) as indic ated by an inhibition study using aminooxyacetic acid. Possible involvement of the thiol compound in the development of an adverse effect is discussed . (C) 2001 Wiley-Liss, Inc.