o-Hydroxyphenylethanol, a novel lactone ring-opened metabolite of coumarin.
A novel metabolite of coumarin was isolated by high pressure liquid chromatography from in vitro incubations with a rat liver 10,000g postmitochondrial supernatant fraction. Mass spectral analysis and co-chromatography with authentic reference compound was utilized to identify the lactone ring-opened metabolite as o-hydroxyphenylethanol. Formation of this metabolite required both the microsomal and cytosolic fractions and the maximum rate of production was observed in the presence of both NADPH and NADH. Analysis of urine from rats administered [14C]coumarin established that o-hydroxyphenylethanol was formed in vivo and the amount excreted was about 15% of that of o-hydroxyphenylacetic acid, the major urinary metabolite. Precursor-product relationship studies indicated that o-hydroxyphenylethanol was readily converted to o-hydroxyphenylacetic acid both in vivo and in vitro while the reverse reaction was not observed. The relationships of these results to the currently accepted pathway(s) leading to ring-opened coumarin products are discussed.
D000818:Animals; D001711:Biotransformation; D002855:Chromatography, Thin Layer; D003374:Coumarins / Q000378:metabolism*; D000431:Ethanol / Q000031:analogs & derivatives*; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D003374:Coumarins; D000431:Ethanol; C043584:2-hydroxyphenylethanol; C030123:coumarin; D010626:Phenylethyl Alcohol