Inhibition of D-3-aminoisobutyrate-pyruvate aminotransferase by 5-fluorouracil and alpha-fluoro-beta-alanine.
Among pyrimidine derivatives, we found that 5-fluorouracil potently inhibited purified rat liver D-3-aminoisobutyrate-pyruvate aminotransferase, whereas 5-fluorouridine did so to a much lesser extent. 5-Fluorouracil acted as a competitive inhibitor against beta-alanine with a Ki of 56 microM, and was uncompetitive against pyruvic acid, with a Ki of 73 microM. alpha-Fluoro-beta-alanine, a metabolite of 5-fluorouracil, was also a competitive inhibitor with respect to beta-alanine with a Ki of 8.0 mM. 5-Fluorouracil acted also as a competitive inhibitor of 4-aminobutyrate aminotransferase with respect to beta-alanine with a Ki value of 1.9 mM, and was uncompetitive against 2-oxoglutaric acid, with a Ki of 1.8 mM.
Kaneko
M
M
Faculty of Nutrition, Kobe-Gakuin University, Japan.
Kontani
Y
Y
Kikugawa
M
M
Tamaki
N
N
D000410:Alanine Transaminase / Q000037:antagonists & inhibitors; D000818:Animals; D005472:Fluorouracil / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D051381:Rats; D013941:Thymine / Q000031:analogs & derivatives; D000637:Transaminases / Q000037:antagonists & inhibitors*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
D015091:beta-Alanine; C032348:alpha-fluoro-beta-alanine; D000637:Transaminases; D000410:Alanine Transaminase; C019685:D-3-aminoisobutyrate-pyruvate aminotransferase; D013941:Thymine; D005472:Fluorouracil