title: Assessment of arylamine N-acetyltransferase (NAT1) activity in mononuclear leukocytes of cystic fibrosis patients.
abstract: The clearance of sulphamethoxazole (SMX), a compound metabolised primarily by the N-acetyltransferase NAT1, is increased in cystic fibrosis (CF) patients. We assessed the activity and kinetic properties of NAT1 in lysates of peripheral blood mononuclear leukocytes (MNL) from CF (n = 17) and control (n = 22) subjects using SMX and p-aminobenzoic acid (PABA) as test substrates. The Km and Vmax values of both substrates in MNL from CF patients and control subjects were not significantly different. The acetylation of PABA (100 microM) by intact MNL from CF patients (n = 4) was not different from the observed in intact MNL from controls (n = 9) (25 +/- 3 pmol h-1 per 10(6) MNL vs 27 +/- 4 pmol h-1 per 10(6) MNL). These results suggest that there are not systemic changes in this enzyme in CF. The increased metabolic clearance of SMX may therefore be related to factors other than alterations in the level of activity of the N-acetyltransferase NAT1.
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: A E
authors.initials: AE
authors.lastname: Cribb
authors.forename: B
authors.initials: B
authors.lastname: Tsui
authors.forename: R
authors.initials: R
authors.lastname: Isbrucker
authors.forename: R T
authors.initials: RT
authors.lastname: Michael
authors.forename: C T
authors.initials: CT
authors.lastname: Gillespie
authors.forename: J
authors.initials: J
authors.lastname: Brown-Bonomo
authors.forename: P
authors.initials: P
authors.lastname: Barrett
authors.forename: T
authors.initials: T
authors.lastname: Levatte
authors.forename: K W
authors.initials: KW
authors.lastname: Renton
mesh_terms: D010129:4-Aminobenzoic Acid / Q000378:metabolism*; D000107:Acetylation; D000293:Adolescent; D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000097:blood*; D002499:Centrifugation, Density Gradient; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D003550:Cystic Fibrosis / Q000201:enzymology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D013420:Sulfamethoxazole / Q000378:metabolism*
chemical_list: D001191:Arylamine N-Acetyltransferase; D013420:Sulfamethoxazole; D010129:4-Aminobenzoic Acid