The metabolism and physiological disposition of radioactively labelled folate derivatives in the rat

Simple method for the quantitative analysis of endogenous folate catabolites p-aminobenzoylglutamate (pABG) and its acetamido (apABG) derivative in human serum and urine by liquid chromatography-tandem mass spectrometry

“…Of all the folate metabolites present in the urine, only apABG persisted at high levels for the 10-day period of the experiment. This finding is corroborated by the works of Connor et al [13] and Pheasant et al [14,15].…”

The metabolism of 5-methyltetrahydropteroyl-l-glutamic acid and its oxidation products in the rat

“…The experiments with 5-CH3-H4PteGlu labelled in the folate skeleton show that this portion of the molecule is assimilated into the folate pool, as shown by the formation of formylfolate in urine and polyglutamates in the tissues, and is degraded by scission to the same catabolites as pteroyl-Lglutamic acid (Murphy et al, 1976;Connor et al, 1979). This is the first report of the catabolism of a naturally occurring reduced folate and supports the model of folate metabolism proposed by Pheasant et al (1981). The observation of elevated 3H/'4C ratios in the excreted folates also suggests that the secondary isotope effect observed during the intestinal transport and metabolism of folic acid (Connor et al, 1980) is not restricted to oxidized folates.…”

“…PteGlu at 100ug/kg body wt., 10%; Pheasant et al, 1981). Also the methyl group of 5-'4CH3-H4PteGlu was not incorporated into polyglutamates, suggesting that demethylation must occur before polyglutamate synthesis.…”

“…The recovery of radioactivity from both doses of the mixed-label compound shows an excess of 14C over 3H in the faeces and the reverse in urine ( Table 3). Chromatography of the urine showed the presence of the following radioactive species: 10formyl-PteGlu, 5-CH3 H4PteGlu, an unidentified dual-labelled species, p-acetamidobenzoyl-L-glutamate and p-acetamidobenzoate (for further details of the identifications, see Pheasant et al, 1981). The distribution of these metabolites is given in Table 4.…”

Folate metabolism in man: the effect of malignant disease

“…Earlier investigations by Ratanasthien et al (1974), using a microbiological assay, showed no metabolism of orally administered 10-formylfolate by man. However, Pheasant et al (1981) found that radiolabelled 10-formylfolate was incorporated into the reduced folate pool of the rat. Further studies undertaken using radiolabelled 10-formylfolate in man, to resolve these apparent discrepancies, are described here.…”