Acetazolamide inhibition of renal γ-glutamyl transpeptidase

Academic Article

Abstract

  • The effect of acetazolamide (AZ) on renal γ-glutamyl transpeptidase (EC 2.3.2.2) activity (γ-GT) was studied with the purified enzyme, subcellular fractions, and in the isolated functioning kidney. Activity of γ-GT was assessed using either one of two γ-glutamyl donors, γ-glutamyl-p-nitroanilide (γGpNA) or glutamine, and either the γ-glutamyl acceptor glycylglycine (Gly-Gly) or methionine (Met). With the microsomal enzyme and β-GpNA, AZ was shown to inhibit p-nitroaniline (p-NA) formation; however, γ-GpNA Km remained unchanged (1.8 mM), while the Vmax was reduced significantly, 333 vs 200 μmoles·min-1·mg-1. Adding Gly-Gly removed AZ inhibition, while AZ elevated the apparent Km for Gly-Gly from 16 to 48; AZ inhibition of γ-GT activity resulted in a decrease in γ-glutamyl-Gly-Gly formation consistent with interaction at the γ-glutamyl acceptor site. With glutamine as the β-glutamyl donor, AZ reduced NH3 and apparent γ-glutamylmethionine formation in the purified enzyme in agreement with inhibition at the acceptor site. In the functioning kidney, perfused with 10-3 M l- or d-glutamine, AZ (10-3 M) markedly reduced NH3 formation and increased glutamine excretion results consistent with AZ inhibition of the in situ γ-GT. © 1982.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Thornley-Brown D; Dass PD; Welbourne TC
  • Start Page

  • 3347
  • End Page

  • 3352
  • Volume

  • 31
  • Issue

  • 21