ASSESSMENT OF ARYLAMINE N-ACETYLTRANSFERASE (NAT1) ACTIVITY IN MONONUCLEAR LEUKOCYTES OF CYSTIC-FIBROSIS PATIENTS

The clearance of sulphamethoxazole (SMX), a compound metabolised prima rily 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 aci d (PABA) as test substrates, The K-m and V-max values of both substrat es in MNL from CF patients and control subjects were not significantly different. The acetylation of PABA (100 mu M) by intact MNL from CF p atients (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 systemi c changes in this enzyme in CE The increased metabolic clearance of SM X may therefore be related to factors other than alterations in the le vel of activity of the N-acetyltransferase NAT1.