NITRIC-OXIDE REVERSIBLY SUPPRESSES XANTHINE-OXIDASE ACTIVITY

The effects of nitric oxide (NO) on xanthine oxidase (XOD) activity an d the site(s) of the redox center(s) affected were investigated. XOD a ctivity was determined by superoxide (O-2(-)) generation and uric acid formation. NO reversibly and dose-dependently suppressed XOD activity in both determination methods. The suppression interval also disclose d a dose-dependent prolongation. The suppression occurred irrespective of the presence or absence of xanthine; indicating that the reaction product of NO and O-2(-), peroxynitrite, is not responsible for the su ppression. Application of synthesized peroxynitrite did not affect XOD activity up to 2 mu M. Methylene blue, which is an electron acceptor from Fe/S center, prevented the NO-induced inactivation. The results i ndicate that NO suppresses XOD activity through reversible alteration of the flavin prosthetic site.