Flavin-containing monooxygenase 3 (FMO3) role in busulphan metabolic pathway
Fig 2
Concentration-time curves for tetrahydrothiophene and its three metabolites after incubation with recombinant FMO3.
Microsomes with cDNA-expressed human FMO3 were incubated with 25μM tetrahydrothiophene (THT). A time curve (0, 5, 15, 30 and 60min) was performed with triplicate incubations and a protein concentration of 0.35mg/mL. 96% of THT was metabolized by recombinant FMO3 in 15 min. The disappearance was accompanied by the formation of metabolites, mainly THT 1-oxide. The other two metabolites (sulfolane and 3-OH-sulfolane) started to appear at later time points, in line with sequential metabolism. (□) THT, solid line; (Δ) THT 1-oxide, dash/dotted; (○) sulfolane, dotted; (◊) 3-OH-sulfolane, solid line.