Hydrolysis of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate at pH 2.5 to 4.5.
At pH 4.0 to 4.5, 5,10-methenyltetrahydrofolate is hydrolyzed to only 5-formyltetrahydrofolate if reducing agents are present or iron-redox cycling is suppressed. At pH 4.0, the equilibrium position for this hydrolysis is approximately equal concentrations of both folates. If no reducing agents are used or iron-redox cycling is promoted, considerable amounts of 10-formyldihydrofolate are also formed. It is likely that 10-formyldihydrofolate has been misidentified as 5,10-hydroxymethylenetetrahydrofolate, which was reported to accumulate during the hydrolysis of 5, 10-methenyltetrahydrofolate to 5-formyltetrahydrofolate [Stover, P. and Schirch, V. (1992) Biochemistry 31, 2148-2155 and 2155-2164; (1990) J. Biol. Chem. 265, 14227-14233]. Since 5, 10-hydroxymethylenetetrahydrofolate is reported to be the viable in vivo substrate for serine hydroxymethyltransferase-catalyzed formation of 5-formyltetrahydrofolate, and 5, 10-hydroxymethylenetetrahydrofolate probably does not accumulate, the above folate metabolism is now doubtful. It is hypothesized that mildly acidic subcellular organelles provide an environment for the hydrolysis of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate in vivo, and there is no requirement for enzyme catalysis. Finally, 10-formyltetrahydrofolate is susceptible to iron-catalyzed oxidation to 10-formyldihydrofolate at pH 4 to 4.5.
Baggott
J E
JE
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
D001205:Ascorbic Acid / Q000737:chemistry; D002021:Buffers; D002850:Chromatography, Gel; D002951:Citrates / Q000737:chemistry; D004226:Dithioerythritol / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry; D005575:Formyltetrahydrofolates / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D010710:Phosphates / Q000737:chemistry; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D013763:Tetrahydrofolates / Q000737:chemistry*
D002021:Buffers; D002951:Citrates; D005575:Formyltetrahydrofolates; D010710:Phosphates; D012996:Solutions; D013763:Tetrahydrofolates; D004226:Dithioerythritol; C018092:5,10-methenyltetrahydrofolate; D005492:Folic Acid; C120486:10-formyl-7,8-dihydrofolic acid; D001205:Ascorbic Acid