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Nonenzymatic Degradation and Salvage of Dietary Folate: Physicochemical Factors Likely to Influence Bioavailability

1995; Academic Press; Volume: 55; Issue: 1 Linguagem: Inglês

10.1006/bmme.1995.1030

1095-5577

Mark Lucock, M. Priestnall, Ioannis Daskalakis, C.J. Schorah, Jennifer Wild, Malcolm I. Levene,

Fluoride Effects and Removal

We investigated the oxidative degradation pathway of 5CH3-H4PteGlu, the main extracellular folate and the predominant form of the vitamin found in food and blood, BCH3-H4PteGlu is oxidized to 5CH3-5,6-H2PteGlu which subsequently undergoes C9-N10 bond cleavage yielding a pteridine residue and P-ABG, the latter step resulting in irreversible loss of vitamin activity. Under moderately acid conditions typical of the postprandial gut (pH 3.5) 5CH3-H4PteGlu is fairly stable (t12 = 273.6 min), while 5CH3-5,6-H2PteGlu is rapidly degraded (t12 = 16.9 min). In a neutral environment (pH 6.4) stability is reversed; 5CH(3)-H(4)PteGlu t12 = 12.0 mins, 5CH3-5,6-H2PteGlu t12 = 1504.6 min. Ascorbic acid was efficacious in the facile salvage of 5CH3-H4PteGlu from 5CH3-5,6-H2PteGlu which occurred rapidly and with significant efficiency (100% conversion) under acid (pH 3.5) conditions, t12 = 1.3 min (1 mmol/liter ascorbate), but was less efficient under neutral (pH 6.4) conditions t12 = 273.6 min (36% conversion). The presence of zinc and iron broadly maintains the pattern of effect, but increases all reaction rates. PteGlu was stable under all conditions studied. These results obtained in an artificial environment were supported by findings in human gastric juice: at a gastric pH of 1.47 with low endogenous ascorbate (7.0 μmol/liter), 5CH3-5,6-H2PteGlu and 5CH3-H4PteGlu both degrade instantly via C9-N10 bond cleavage to yield an equimolar amount of P-ABG. If the same gastric juice is spiked at 58.0 μmol/liter ascorbate (moderate endogenous concentration), 5CH3-H4PteGlu is stable (t12 = 334.7 min), while 5CH3-5,6-H2PteGlu is instantly salvaged to 5CH3-H4PteGlu with 43.3% efficiency, and the remaining 5CH3-5,6-H2PteGlu is degraded to P-ABG. In gastric juice with an elevated pH of 7.0 and no endogenous ascorbate, 5CH3-5,6-H2PteGlu and 5CH3-H4PteGlu are both stable, with no C9-N10 bond cleavage. This, for 5CH3-H4PteGlu, is in apparent contrast to findings at pH 6.4 in an artificial environment. The same gastric juice spiked to 50 μmol/liter ascorbate did not result in 5CH3-H4PteGlu salvage from 5CH3-5,6-H2PteGlu. These results may represent evidence of a biological role for gastric ascorbic acid in maintaining efficient folate bioavailability from dietary sources which reportedly contain significant amounts of folate as 5CH3-5,6-H4PteGlu. The clinical aspects of such an intimate relationship between gastric ascorbate and dietary folate are discussed, as are the implications for interpretation of bioavailability studies using nondiscriminatory folate assays which incorporate ascorbate into the assay procedure and thus convert metabolically inactive 5CH3-5,6-H2PteGlu into active 5CH3-H4PteGlu.