The elucidation of the mechanism of folate catabolism in the rat

Murphy, Maryanne; Keating, Mary A.; Boyle, P.; Weir, Donald G.; Scott, John M.

doi:10.1016/0006-291x(76)90756-7

Cited by 70 publications

(40 citation statements)

References 17 publications

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“…If the radioactivity not recovered in the urine or faeces is retained in the tissues, man excretes a higher percentage of the tissue folates as scission products than the rat (Table IV). This is consistent with the suggestion that catabolism proceeds via oxidative cleavage on the C9-NIO bond (Murphy et al, 1976;Saleh et al, 1981 since the hepatic NAD/NADH ratio is higher in man than rat (R. A. Harris, personal communication).…”

Section: Discussionsupporting

confidence: 79%

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Folate metabolism in man: the effect of malignant disease

Saleh¹,

Pheasant²,

Blair³

et al. 1982

Br J Cancer

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The metabolism of [2-14C]+[3', 5', 7, 9-3H] folic acid and [214C]+[3', 5', 7, 9-3H] 10-formylfolate was studied in hospital inpatients. Metabolites detected in the urine after folic acid feeding included the unchanged compound, other folates and a number of breakdown products, such as p-acetamidobenzoyl-L-glutamate and p-acetamidobenzoate. This confirms the existence of a folate catabolic pathway in man. Patients with malignant disease excreted less of the dose in urine, incorporated more into the reduced folate pool, and showed decreased catabolism of folate, when compared to controls. 10-Formylfolate was excreted largely unchanged, and appears not to be reduced by man. Also 10-formylfolate interfered with the reduction of folic acid given simultaneously.

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Section: Discussionsupporting

confidence: 79%

“…There have been no detailed studies since the introduction of the unambiguous technique of using a mixture of 14C-and 3H-labelled species by ourselves, and the recognition of a breakdown process as a major route of metabolism of folates in the rat (Murphy et al, 1976;Connor et al, 1979).…”

mentioning

confidence: 99%

Folate metabolism in man: the effect of malignant disease

Saleh¹,

Pheasant²,

Blair³

et al. 1982

Br J Cancer

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“…p-Acetamidobenzoate and p-acetamidobenzoyl-L-glutamate (Murphy et al, 1976) have been identified as catabolites of 3H folate tracers; pterin and isoxanthopterin have been detected after folic acid administration (Fukushima & Shiota, 1972;Krumdieck et al, 1978) and reported an unidentified pteridine as a metabolite of 3H-and 14C-folic acid.…”

mentioning

confidence: 99%

Folate catabolism in tumour-bearing rats and rats treated with methotrexate

Saleh¹,

Pheasant²,

Blair³

1981

Br J Cancer

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The metabolism of (2-14C) + (3',5',7,9-3H) folic acid was studied in normal rats, tumour-bearing rats and rats treated with methotrexate (MTX). The experiments were designed to investigate changes in the catabolism and folate. The breakdown of folate to scission products was again demonstrated to be a normal phenomenon. Catabolites excreted included p-acetamidobenzoate, p-acetamidobenzoyl-L-glutamate, 3H2O, urea and a number of pterins. The catabolic process was decreased in the presence of a tumour and increased by the administration of MTX. MTX also led to the excretion of 4 additional radioactive pterins not found in normal urine. The possible mechanisms of folate breakdown are discussed with reference to the point of action of MTX.

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“…Recently, fragmentation products of folates have been reported in rat urine after doses of either 3',5',9-[3H]-folic acid (Murphy et al, 1976) or a mixture of 2-[14C]-and 3',5',9-[3H]-10-formylfolate tetraglutamate (Connor et al, 1977 Collection of urine and faeces-Urine was collected into flasks containing 10 ml of phosphate buffer (pH 7-0) with 2% (w/v) sodium ascorbate and 0-005%o (w/v) of dithiothreitol.…”

mentioning

confidence: 99%