XENOBIOTIC BIOTRANSFORMING ENZYMES IN THE CENTRAL-NERVOUS-SYSTEM - ANISOFORM OF FLAVIN-CONTAINING MONOOXYGENASE (FMO4) IS EXPRESSED IN RABBIT BRAIN

The flavin-containing monooxygenase (FMO, EC 1.14.13.8) is involved in the metabolism of a number of important xenobiotics including many wh ich affect the central nervous system (CNS). Recently, reports in the literature concerning the amount, activity, location, and isozyme char acteristics of this enzyme in the brain have presented conflicting evi dence. In order to resolve some of the controversy surrounding FMO in the brain, a highly sensitive method for the detection of flavin-conta ining monooxygenase (FMO) mRNA in whole brain was employed. A poorly c onserved region of FMO transcripts was used to design five sets of oli gonucleotide primers. Each primer set was specific for one of the five currently known isoforms of FMO. Four and five isoforms, respectively , are expressed in rabbit liver and kidney, as determined by reverse t ranscription-polymerase chain reaction. However, only one set of prime rs amplified a specific rabbit brain cDNA fragment. The sequence of th e amplification product affirmed its identity as a segment of FMO4 cDN A. Thus, the FMO of rabbit brain may consist of a single, as yet uncha racterized isozyme and, contrary to several recent reports, is likely to be expressed at low levels.