Arylamine N-acetyltransferase in erythrocytes of cystic fibrosis patients.
Sulphamethoxazole, a substrate of human arylamine N-acetyltransferase, is used in the treatment of cystic fibrosis patients, who metabolise the drug rapidly. Increased metabolic clearance of sulphamethoxazole has been suggested to account for this rapid metabolism. Arylamine N-acetyltransferase type 1 is expressed in erythrocytes and leucocytes and the activity in erythrocytes is shown to contribute approximately 99% of the activity of arylamine N-acetyltransferase type 1 in blood cells. Arylamine N-acetyltransferase type 1 activity in erythrocytes from 16 adult cystic fibrosis patients and 19 age-matched controls were compared. Although there is a variation in erythrocyte arylamine N-acetyltransferase type 1 activity within each group, no difference was found when the two groups were compared. All individuals from the cystic fibrosis and control groups were investigated for certain allelic variants of the arylamine N-acetyltransferase type 1 gene (NAT1). Only one copy of a mutant NAT1 allele (NAT1*11) was found. The heterozygous NAT1 individual is a cystic fibrosis patient with a low level of erythrocyte arylamine N-acetyltransferase type 1 activity. A second distinct arylamine N-acetyltransferase isozyme, arylamine N-acetyltransferase type 2, is encoded at the multi-allelic NAT2 locus. There was no correlation between erythrocyte arylamine N-acetyltransferase-1 activity and NAT2 alleles present in either the cystic fibrosis or control groups. The distribution of NAT2 alleles was very similar in the two groups. The increased clearance of sulphamethoxazole in cystic fibrosis patients appears unlikely to be due to erythrocyte arylamine N-acetyltransferase type 1 activity or to inheritance of alleles at either the NAT1 or NAT2 loci.
Risch
A
A
Department of Pharmacology, University of Oxford, UK.
Smelt
V
V
Lane
D
D
Stanley
L
L
van der Slot
W
W
Ward
A
A
Sim
E
E
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000890:Anti-Infective Agents / Q000378:metabolism; D001191:Arylamine N-Acetyltransferase / Q000097:blood* / Q000235:genetics*; D003550:Cystic Fibrosis / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000097:blood* / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013420:Sulfamethoxazole / Q000378:metabolism
D000890:Anti-Infective Agents; D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D013420:Sulfamethoxazole