Evidence of a new metabolic pathway of 5-fluorouracil in Escherichia coli from in vivo 19F-NMR spectroscopy.
Two distinct metabolic pathways of 5-fluorouracil are proposed in Escherichia coli. The first metabolic pathway is a reductive degradation with the formation of dihydrofluorouracil as the first metabolite. The second metabolic pathway is shown to be a hydroxylating degradation, possibly with the formation of 5-hydro-6-hydroxy-5-fluorouracil as the first metabolite. The metabolites of both pathways undergo subsequent hydrolytic degradation with fluoride ion as the common final product. The chemical structures of these metabolites were partially identified by 19F-NMR. The results show a close resemblance between these two metabolic pathways with in vivo pyrimidine biodegradation. The reductive degradation has been proposed by several laboratories, whereas the hydroxy degradation has not been reported before. Both the reductive and hydroxy pathways are demonstrated in this report, to be independent reactions.
Lee
K R
KR
Institute of Life Science, National Tsing Hua University, Hsin-Chu, Taiwan, China.
Sheu
S Y
SY
D004926:Escherichia coli / Q000378:metabolism*; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000378:metabolism*; D006900:Hydroxylation; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy
C019389:5-fluorodihydrouracil; D005472:Fluorouracil