Enzymatic studies on the metabolism of the tetrahydrofurfuryl mercaptan moiety of thiamine tetrahydrofurfuryl disulfide, 3

In vitro metabolism of the tetrahydrofuran ring was studied using [35S]methyl tetrahydrofurfuryl sulfone as a substrate with rat liver homogenates. The tetrahydrofuran ring was first hydroxylated by liver microsomes in the presence of NADPH and O2. The reaction product was isolated and identified as methyl 5-hydroxytetra-hydrofurfuryl sulfone by instrumental analyses of the infrared, nuclear magnetic resonance, and mass spectra. An NADH-generating system could not support this microsomal hydroxylation, and the involvement of a peroxidative reaction was excluded. Methyl 5-hydroxytetrahydrofurfuryl sulfone thus formed was further oxidized to 4-hydroxy-5-methylsulfonylvaleric acid by incubation with the hepatic cytosol. Microsomes were no longer necessary for the second reaction. These results indicated that the tetrahydrofuran ring was first hydroxylated at the 5-position by microsomes and further cleaved to the straight-chain fatty acid via the intermediate formation of either an aldehyde form or a 7-lactone in the presence of cytosol.