The formaldehyde-donating activity of N5,N10-methylene tetrahydrofolic acid in xenobiotic biotransformation.
Reaction of reproterol, (7-(3-[2-(3,5-dihydroxyphenyl)-2-hydroxyethylamino]propyl)theophyl line (I), with formaldehyde liberated in a solution of N5,N10-methylene tetrahydrofolic acid at pH 7.3 led to the formation of 7-[3-(4,6,8-trihydroxy-1,2,3,4-tetrahydroisoquinolinyl-2)propyl]th eophylline (II), but no such reaction was observed in a solution of N5-methyl tetrahydrofolic acid. Compound II was also formed by incubation of I with rat-liver subcellular fractions. The highest formaldehyde-donating activity was found in the soluble fraction but some activity was also observed with washed mitochondria and microsomes. Dimedone was transformed to methylene bisdimedone by incubation with the soluble fraction. The amount of formaldehyde liberated in the soluble fraction during a four hour incubation at 22 degrees C was 1-3.6 mumol/g of liver. Metaproterenol and terbutaline, structurally related to I, reacted with formaldehyde to yield the corresponding tetrahydro-isoquinolines. The rate of this chemical reaction for the three drugs correlated with the amount of the tetrahydroquinolines formed by incubation with the soluble fraction and in orally dosed rats.
D000818:Animals; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D003600:Cytosol / Q000378:metabolism; D004355:Drug Stability; D005557:Formaldehyde / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism*; D008297:Male; D009921:Metaproterenol / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013726:Terbutaline / Q000378:metabolism; D013763:Tetrahydrofolates / Q000378:metabolism*
D013763:Tetrahydrofolates; C013123:5,10-methylenetetrahydrofolic acid; D005557:Formaldehyde; D009921:Metaproterenol; D013726:Terbutaline