title: Influence of reducing carbohydrates on (6S)-5-methyltetrahydrofolic acid degradation during thermal treatments.
abstract: The mechanism and kinetics of the degradation of (6S)5-methyl-5,6,7,8-tetrahydrofolic acid in an aqueous solution in the presence of reducing carbohydrates such as glucose and fructose were investigated for thermal treatments. Preliminary experiments indicated that the presence of reducing carbohydrates, especially fructose (1.6 mM-1.5 M), strongly enhanced folate degradation at moderate temperatures (50-90 degrees C, 0-60 min). Identification of the predominant folate degradation products by LC-MS and NMR pointed to the formation of N(2alpha)-[1-(carboxyethyl)]-5-methyl-5,6,7,8-tetrahydrofolic acid diastereomers besides other folate degradation products upon prolonged heating (24 h, 100 degrees C) of (6S)5-methyl-5,6,7,8-tetrahydrofolic acid in fructose or dihydroxyacetone solutions. Using a Bayesian multiresponse kinetic modeling approach, kinetic characterization and elucidation of the degradation mechanism in the presence of equimolar amounts of dihydroxyacetone, fructose, and glucose were achieved. On the basis of the established degradation mechanism for (6S)5-methyl-5,6,7,8-tetrahydrofolic acid oxidation in the literature, it was shown that nonenzymatic glycation occurred due to reaction of dihydroxyacetone with 5-methyl-7,8-dihydrofolic acid. During thermal treatments (85-110 degrees C, 0-60 min), the nonenzymatic glycation reaction was characterized by an activation energy of 61.3 +/- 9.3 and 77.6 +/- 7.8 kJ mol(-1) in the presence of, respectively, dihydroxyacetone and fructose. Addition of L-ascorbic acid (1.13 mM) to folate samples (0.04 mM) with equimolar amounts of fructose prior to heating (100 degrees C, 0-45 min) was shown to retard the formation of 5-methyl-7,8-dihydrofolic acid and hence prevented the formation of the carboxyethylated derivatives under the investigated conditions.
authors.affiliation: Department of Microbial and Molecular Systems, Laboratory of Food Technology, Leuven Food Science and Nutrition Research Centre, Katholieke Universiteit Leuven, Kasteelpark Arenberg 22, Box 2457, 3001 Leuven, Belgium.
authors.forename: Philippe H C J
authors.initials: PH
authors.lastname: Verlinde
authors.forename: Indrawati
authors.initials: I
authors.lastname: Oey
authors.forename: Lien
authors.initials: L
authors.lastname: Lemmens
authors.forename: Wim M
authors.initials: WM
authors.lastname: Deborggraeve
authors.forename: Marc E
authors.initials: ME
authors.lastname: Hendrickx
authors.forename: Ann M
authors.initials: AM
authors.lastname: Van Loey
mesh_terms: D004098:Dihydroxyacetone / Q000494:pharmacology; D004355:Drug Stability; D005492:Folic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006031:Glycosylation; D006358:Hot Temperature; D007700:Kinetics; D010084:Oxidation-Reduction; D012996:Solutions; D013763:Tetrahydrofolates / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water
chemical_list: D012996:Solutions; D013763:Tetrahydrofolates; D014867:Water; D005632:Fructose; C012429:5-methyldihydrofolate; D005492:Folic Acid; D005947:Glucose; D004098:Dihydroxyacetone; C005984:5-methyltetrahydrofolate