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.
Kishida
K
K
Laboratory of Biochemistry and Pharmacology, Osaka Prefecture College of Nursing, 3-7-30 Habikino, Habikino-shi, Osaka 583-8555, Japan. kkishida@osaka-hsu.ac.jp
Saida
N
N
Yamamura
N
N
Iwai
Y
Y
Sasabe
T
T
D000818:Animals; D013437:Carbon-Sulfur Lyases / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D003545:Cysteine / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008704:Methazolamide / Q000737:chemistry / Q000378:metabolism*; D013057:Spectrum Analysis
D002257:Carbonic Anhydrase Inhibitors; D013437:Carbon-Sulfur Lyases; C108902:cysteine-S-conjugate beta-lyase; D003545:Cysteine; D008704:Methazolamide