Folate availability

There are various analytical platforms used to measure folate concentrations in food, each with its advantages and drawbacks. Microbiological assay makes use of bacteria (e.g. Lactobacillus easel) that are very dependent on folate availability for their growth. This assay is commonly used to determine the total folate contents in food, which is expressed in terms of folic acid equivalents. The most important limitation of microbiological assay is that the various vitamers are not distinguishable... 

Biochemical Functions. Ascorbic acid has various biochemical functions, involving, for example, coUagen synthesis, immune function, dmg metabohsm, folate metaboHsm, cholesterol cataboHsm, iron metaboHsm, and carnitine biosynthesis. Clear-cut evidence for its biochemical role is available only with respect to coUagen biosynthesis (hydroxylation of prolin and lysine). In addition, ascorbic acid can act as a reducing agent and as an effective antioxidant. Ascorbic acid also interferes with nitrosamine formation by reacting direcdy with nitrites, and consequently may potentially reduce cancer risk. 

Radiolabeled folate provides a powerful tool for folate bioavaHabiUty studies in animals and for diagnostic procedures in humans. Deuteration at the 3- and 5-positions of the central benzene ring of foHc acid (31) was accompHshed by catalytic debromination (47,48) or acid-cataly2ed exchange reaction (49). Alternatively, deuterium-labeled fohc acid (32) was prepared by condensing pteroic acid with commercially available labeled glutamic acid (50). 

Sulphonamides are structural analogues of PABA. They competitively inhibit the incorporation of PABA into dihydropteroic acid and there is some evidence for their incorporation into false folate analogues which inhibit subsequent metabolism. The presence of excess PABA will reverse the inhibitory action of sulphonamides, as will thymine, adenine, guanine and methionine. However, these nutrients are not normally available at the site of infections for which the sulphonamides are used. 

Milk is an excellent source of calcium, phosphorus, riboflavin (vitamin B2), thiamine (vitamin Bl) and vitamin B12, and a valuable source of folate, niacin, magnesium and zinc (Food Standards Agency, 2002). In particular, dairy products are an important source of calcium, which is vital for maintaining optimal bone health in humans (Prentice, 2004). The vitamins and minerals it provides are all bioavailable (i.e. available for absorption and use by the body) and thus milk consumption in humans increases the chances of achieving nutritional recommendations for daily vitamins and mineral intake (Bellew et al., 2000). 

The DNA-mediated effects of fluropyrimidines can be modulated by a number of agents, such as leucovorin (LV), levamisole, and interferon-alpha (IFN-alpha). LV prolongs TS inhibition by increasing the availability of the reduced folate cofactor necessary for formation of the inactive TS-FdUMP complex (21) (Fig. 4). Studies show alpha-interferon can potentiate 5-FU-mediated cyotoxicity, but the mechanisms are not yet defined (22,23). Another approach to modulate the activity of fluoropyrimidines is the use of the nucleoside transport inhibitor dipyridamole. Dipyridamole probably permits... 

Some commonly used detectors are UV (at 280 nm), ELD, ED and microbiological assay of collected fractions. UV presents a low sensitivity, but all folate derivatives respond to this detection. ELD is used even if some compounds, like folic acid, do not fluoresce. Therefore, a postcolumn derivatization, involving hypochlorite to cleave folic acid, di- and tetra-hydrofolic acid oxidatively to fluorescence pterins [571], has been introduced. Eewer reports on the use of LC-MS for folate detection are available in the literature [578-580]. 

Folic acid is used for the treatment of folate deficiency. Oral folic acid is usually the therapy of choice. For megaloblastic anemia doses of 5 mg daily for 4 months should be effective. Folinic acid is available in a parenteral formulation which may be indicated when oral therapy is not feasible and for rescue treatments following certain anti-cancer regimens. 

Methotrexate inhibits folate metabolism by preventing methylenetetrahydrofolate reductase from converting 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate thus inhibiting thymidylate synthase conversion of dUMP to dTMP. DNA replication is effectively decreased by the diminution of dTMP availability. As shown in Fig. 2, multiple enzymes mediate the folate cycle. Thus, genetic variation in these enzymes may... 

Folacin bioavailability varies among the vitamers (120,125). Folic acid is more readily available than the naturally occurring food folates but may be less available from fortified foods than in aqueous solution or tablet form. Food folates have been reported to be 30-80% as available as folic acid. Folacin availability, absorption, and metabolism were recently reviewed (20,120,122). 

In addition to the larger families of preparatively useful aldolases, some less common aldolases have been evaluated lately for preparative use. A range of mechanistically distinct enzymes, which are actually categorized as transferases but which also catalyze aldol-related additions through the aid of cofactors such as pyridoxal 5-phosphate (PLP), thiamine pyrophosphate (TPP), tetrahydro-folate (THF), or coenzyme A (CoA), are becoming more frequently applied in organic synthesis. Because of their emerging importance and/or commercial availability, a selection of these enzymes and examples of their synthetic utility will be included in further separate chapters. 

Ncphrocaps Ascorbic acid, folate, niacinamide, thiamine iimnuniincf, rihu flavin. pyridoxinc HCI. cyanncnhalamin, calcium ftintulheEiaic. and hiolin Shell cviipAitioii is not available ... 

The availability of erythropoietin has had a significant positive impact for patients with chronic renal failure. Erythropoietin consistently improves the hematocrit and hemoglobin level and usually eliminates the need for transfusions in these patients. An increase in reticulocyte count is usually observed in about 10 days and an increase in hematocrit and hemoglobin levels in 2-6 weeks. Most patients can maintain a hematocrit of about 35% with erythropoietin doses of 50-150 IU/kg intravenously or subcutaneously three times a week. Failure to respond to erythropoietin is most commonly due to concurrent iron deficiency, which can be corrected by giving oral iron. Folate supplementation may also be necessary in some patients. 

While there are no epidemiologic data available on lipotropic factors and colon cancer in human populations, results of animal studies suggest a possible role for this class of nutrients (choline, methionine, vitamin and folate) in colon carcinogenesis (69). Table XVI lists results typical of those observed when rats are fed a diet high in fat, low in lipotropes and exposed to a colon carcinogen. 

Folate in the human organism is converted to tetrahydrofolate (THF or FH4) by a reductive process. The reduction reaction is a stepwise one folate to dihydrofolate, then to THF. A single enzyme, dihydrofolate reductase, catalyzes both steps. The reaction is inhibited by folate analogues and the antitumor agents methotrexate and aminopterin (Figure 6.3). Because THF is required for DNA biosynthesis (Chapter 10) and tumors have a very high level of DNA biosynthetic activity, even modest decreases in THF availability will inhibit tumor growth. 

A 6-month-old infant has been fed unmodified cow s milk supplemented with com flour. He was healthy except that he was severely anemic, and an X-ray of his wrist showed retarded bone development. His hemoglobin was only 4.5 g/dL, and he had an elevated serum alkaline phosphatase. He was treated with iron supplements, folate, and ascorbic acid to no avail. Then serum copper analysis was done, and it showed a level of 9 fig/dL (normal is 85-163 /ig/dL). Thereupon his diet was supplemented with copper sulfate, and he showed dramatic improvement. Address the following questions ... 

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