Folate stabilizers

Milk is not a rich source of dietary folate compared to other foods however, as is the case for riboflavin, folate concentrations can be significantly increased in many dairy products due to microbial fermentation. Among dairy products, fermented milks are considered a good potential matrix for folate fortification because folate-binding proteins present in milk improve folate stability and enhance the bioavailability of both 5-methyltetrahydrofolate (the most predominant natural form of the vitamin) and folic acid (Jones and Nixon 2002 Aryana 2003 Verwei et al. 2003). However, due to the potential risks of fortification with folic acid, the elaboration of fermented milks containing elevated levels of natural folates would be a better suited alternative. 

Coenzymes serve as recyclable shuttles—or group transfer reagents—that transport many substrates from their point of generation to their point of utilization. Association with the coenzyme also stabilizes substrates such as hydrogen atoms or hydride ions that are unstable in the aqueous environment of the cell. Other chemical moieties transported by coenzymes include methyl groups (folates), acyl groups (coenzyme A), and oligosaccharides (dolichol). 

The stability of [3, 5, 7,9-3H]folic acid (Fignre 10.10) was analyzed to determine whether the varied and conflicting resnlts regarding the characteristics of folate transport in L1210 cells conld be due to impurities in the labeled snbstrate [19]. The susceptibility of [3, 5, 7,9-3H]folic acid to decomposition during storage at -20°C... 

TK), 5-FU is activated to 5-fluorodeoxyuridine monophosphate (5-FdUMP). Potent inhibition of thymidylate synthase (TS) by 5-FdUMP is considered critical for 5-FU cytotoxicity. TS catalyzes the rate-limiting step of DNA synthesis, such as the conversion of dUMP into dTMP. Optimal TS function requires the formation of a covalent ternary complex consisting of TS, the folate cofactor 5,10-methylenetetra-hydrofolate (CH2THF), and 5-FdUMP. Inadequate cellular levels of 5,10-methyle-netetrahydrofolate reduce the stability of the ternary complex and consequently the inhibition of TS by 5-FdUMP. For this reason, 5-FU is administered in association with folinic acid, a precursor of 5,10-methylenetetrahydrofolate [40]. 

Recently a great deal of effort has been spent in studying the metabolism of leucovorin in vivo. This emphasis was prompted by the chemical stability of this folate and by the observation of a reduction in toxicity of methotrexate when it was given in conjunction with leucovorin. Fol-inic acid is found in human liver, but it is not the major circulating folate, which is 5-methyltetrahydrofolate. 

Folate is the generic name used to refer to a family of vitamers with related biological activity. Instead, folic acid (pteroylglutamin acid, PGA) (Fignre 19.16) refers to the most oxidized, stable, and easily adsorbable synthetic form (monoglutamate). It is commonly nsed in food supplements and in food fortification because of its stability and becomes biologically active after redaction. 

The major sources of folate are green vegetables, citrus fruits, legumes, egg yolk, wheat germ, and yeast [417]. This vitamin can be added only in the form of pteroylmonoglutamic acid [402]. The multiplicity of forms, low stability, low concentration, and the complex extraction and detection techniques make the analysis of folate in food a difficult task. 

Jones, M. L, Nixon, P. F. (2002). Tetrahydrofolates are greatly stabilized by binding to bovine milk folate-binding protein. J. Nutr., 132,2690-2694. 

Folate is sensitive to light and may be subject to photodecomposition. Heat treatment influences folate levels in milk. Pasteurization and the storage of pasteurized milks have relatively little effect on the stability of folate but UHT treatments can cause substantial losses. The concentration of oxygen in UHT milk (from the headspace above the milk or by diffusion... 

JG Hawkes, R Villota. Folates in foods reactivity, stability during processing, and nutritional implications. CRC Crit Rev Food Sci Nutr 28 439-540, 1989. 

METHOTREXATE ANTIMALARIALS -PYRIMETHAMINE t antifolate effect of methotrexate Pyrimethamine should not be used alone and is combined with sulfadoxine. Pyrimethamine and methotrexate synergistically induce folate deficiency Although the toxic effects of methotrexate are more frequent with high doses of methotrexate, it is necessary to do an FBC, liver and renal function tests before starting treatment even with low doses, repeating these tests weekly until therapy is stabilized and thereafter every 2-3 months. Patients should be advised to report symptoms such as sore throat and fever immediately, and also any gastrointestinal discomfort. A profound drop in white cell count or platelet count warrants immediate stoppage of methotrexate therapy and initiation of supportive therapy... 

Yoo, H.S. Park, T.G. Folate-receptor-targeted delivery of doxorubicin nano-aggregates stabilized by doxorubicin-PEG-folate conjugate. Journal of Controlled Release... 

B Fluorouracil is a prodrug that is metabolized to FdUMP and a triphosphate metabolite. FdUMP binds and interferes with thymidylate synthase, whereas the triphosphate metabolite interferes with RNA function. Leucovorin is a reduced form of folic acid. Leucovorin provides folate cofactors that stabilize the binding of FdUMP and thymidylate synthase, thus enhancing the cytotoxic effects of fluorouracil. 

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