Ibuprofen inhibits arylamine N-acetyltransferase activity in the bacteria Klebsiella pneumoniae.
Ibuprofen, one of the nonsteroidal anti-inflammatory drugs, inhibited arylamine N-acetyltransferase activity of Klebsiella pneumoniae both in vitro and in vivo. The NAT activities of Klebsiella pneumoniae were inhibited by ibuprofen in a dose-dependent manner both in vitro and in vivo. In vitro, the NAT activity was 0.675 +/- 0.028 nmol/min/mg of protein for the acetylation of 2-aminofluorene. In the presence of 8 mM ibuprofen, the NAT activity was 0.506 +/- 0.002 nmol/min/mg of protein for the acetylation of 2-aminofluorene. In vivo, the NAT activity was 0.279 +/- 0.016 nmol/min/10(10) colony forming units (CFU) for the acetylation of 2-aminofluorene. In the presence of 8 mM ibuprofen, the NAT activity was 0.228 +/- 0.008 nmol/min/10(10) CFU for the acetylation of 2-aminofluorene. The inhibition of NAT activity by ibuprofen was shown to persist for at least 4 h. For in vitro examination, the values of apparent Km and Vmax were 1.08 +/- 0.05 mM and 9.17 +/- 0.11 nmol/min/mg of protein, respectively, for 2-aminofluorene. However, when 8 mM of ibuprofen was added to the reaction mixtures, the values of apparent Km and Vmax were 1.19 +/- 0.01 mM and 6.67 +/- 0.11 nmol/min/mg of protein, respectively, for 2-aminofluorene. For in vivo examination, the values of apparent Km and Vmax were 1.24 +/- 0.48 mM and 4.18 +/- 1.06 nmol/min/10 x 10(10) CFU, respectively, for 2-aminofluorene. However, when 8 mM of ibuprofen was added to the culture, the values of apparent Km and Vmax were 0.95 +/- 0.29 mM and 2.77 +/- 0.37 nmol/min/mg protein, respectively, for 2-aminofluorene, respectively. This report is the first finding of ibuprofen inhibition of arylamine N-acetyltransferase activity in a strain of Klebsiella pneumoniae.
Chung
J G
JG
China Medical College Hospital, Taichung 400, Taiwan, Republic of China.
Lo
H H
HH
Hsieh
S E
SE
Yen
Y S
YS
D015073:2-Acetylaminofluorene / Q000378:metabolism; D000107:Acetylation; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005449:Fluorenes / Q000378:metabolism; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology* / Q000302:isolation & purification
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D005449:Fluorenes; C012177:2-aminofluorene; D015073:2-Acetylaminofluorene; D001191:Arylamine N-Acetyltransferase; D007052:Ibuprofen