Oxidative degradation of dihydrofolate and tetrahydrofolate

Abstract

degradation of dihydrofolate and tetrahydrofolate.Can. J. Biochem. 43,999-1009Biochem. 43,999- (1970. 7,8-Dihydrofolate has been degraded oxidatively using ferricyaniae under anaerobic conditions. Three reaction pathways have been found for this oxidation, and these pathways can be controlled by variation of the pH and by the nature of the buffer anion. At pH 9, treatment s f dihydrofolate with two equivalents of ferricyanide leads to quantitative formation of folate. At pH 5.6 in morpholinoethanesulfonic acid buffer, the same reactants produce p-arninobenzoylglutarnate, dihydrsxanthogterin, and formaldehyde. Each of these products has been identified, and isolated in high yield. 6-Formyldihydropterin can be isolated by oxidation of dihydrofolate in either phosphate or carboxylic acid buffers. This compound does not appear to be an intermediate in the formation of dihydroxanthopterin under the conditions of our experiments. Tetrahydrofolate was also degraded oxidatively using ferricyanide. Although it is more susceptible to cleavage than is dihydrofolate, tetrahydrofolate gives similar products. In addition, moderate quantities of pterin were isolated from oxidation of tetrahydrofolate at pH 5.6.

Reduced 6,6,8‐Trimethylpterins

“…It has been shown that tetrahydrofolic acid decomposes in aqueous buffer under oxidative conditions to give 7,8-dihydroxanthopterin and pterin [15,161. We believe that loss of the p-aminobenzoylglutamic acid side chain occurs from the quinonoid form of dihydrofolic acid in an analogous manner to the loss of the dihydroxypropyl side chain from q-BH2 [4] (259.…”

Purification and Properties of a Folate-catabolizing Enzyme

“…This suggestion is supported by the observation that the addition of EDTA to the homogenization buffer eliminated 5-formyl-THF catabolic activity in rat liver extracts. Ferric iron is an oxidant, and some studies have demonstrated that non-ferritin-bound iron catalyzes the oxidation of folate derivatives in vitro (6,39). Passage of purified ferritin through a 0.5 ϫ 2-cm Chelex 100 cation affinity column to remove non-ferritin-bound iron did not diminish the catalytic activity, indicating that if iron is a catalyst, it functions only when bound to ferritin.…”

“…Oxidation can occur by at least two distinct mechanisms that are essentially irreversible. The quinazoline ring can be sequentially oxidized to dihydrofolate and then to folic acid through a quinonoid dihydrofolate intermediate (5,6). This mechanism is also shared by tetrahydropterin oxidation (7,8).…”

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

“…to an increased produc-ing binding proteins, and/or to the inhibiblled p-acetamidobenzoyl-tion of uptake of folates into cells (Goldhe catabolic rate remained man, 1971). MTX also increased the eas 4.4% of the radio-catabolism of folate, which is seen as an the tissues after 8 h was increase in urinary catabolites, particu-,cetamidobenzoyl-L-gluta-larly p-acetamidobenzoyl-L-glutamate tumour-bearing animals, (28% of the activity retained in the tissues >% for the controls (Table after hyde, p-aminobenzoyl-L-glutamate, dihydroxanthopterin and 7,8-dihydropterin-21-1 5 9 28-0 6-carboxaldehyde (Chippel & Scrimgeour, 1970). The dihydro derivatives are likely the folate molecule most to oxidize further, giving xanthopterin ds by oxidative scission and pterin-6-carboxylic acid respectively.…”