Folic acid folate, derivatives

Folic acid derivatives (folates) are acceptors and donors of one-carbon units for all oxidation levels of carbon except that of CO2 (where biotin is the relevant carrier). The active coenzyme form of folic acid is tetrahydrofolate (THF). THF is formed via two successive reductions of folate by dihydrofolate reductase (Figure 18.35). One-carbon units in three different oxidation states may be bound to tetrahydrofolate at the and/or nitrogens (Table 18.6). These one-carbon units... 

Folic acid or folate (Fig. 1) is the collective name for more than 100 derivatives of pteroyl-mono-L-gluta-mate. In plant and animal tissues, folic acid mostly occurs as pteroyloligo-L-glutamate (PteGluJ, with up to eight glutamyl residues. 

The chemical structure of folate (or folic acid) is shown in Figure 5.8. In humans, folate usually occurs as polyglutamate derivatives. The active form of folate is THF, sometimes shown as FH4) is derived from folate via two reductase reactions. THF functions as a carrier of one-carbon groups in varying oxidation states (Table 5.1). 

Recently, Choy et al. also reported that LDHs are an efficient drug reservoir for folate derivatives [187]. Folic acid derivatives, folinic acid and methotrexate (MTX), have been successfully hybridized with Mg/Al LDHs by ion-exchange reactions. Cellular uptake tests with the MTX-LDH hybrids were carried out in the fibroblast (human tendon) and osteosarcoma (SaOS-2) cell lines by in vitro assay. They found that the LDH not only plays a role as a biocompatible delivery matrix for drugs but also facilitates a significant increase in the delivery efficiency. 

These are pyrimidine derivatives and are effective because of differences in susceptibility between the enzymes in humans and in the infective organism. Anticancer agents based on folic acid, e.g. methotrexate, inhibit dihydrofolate reductase, but they are less selective than the antimicrobial agents and rely on a stronger binding to the enzyme than the natural substrate has. They also block pyrimidine biosynthesis. Methotrexate treatment is potentially lethal to the patient, and is usually followed by rescue with folinic acid (A -formyl-tetrahydrofolic acid) to counteract the folate-antagonist action. The rationale is that folinic acid rescues normal cells more effectively than it does tumour cells. 

Folate, the anion of folic acid, is made up of three different components—a pteridine derivative, 4-aminobenzoate, and one or more glutamate residues. After reduction to tetrahydrofolate (THF), folate serves as a coenzyme in the Q metabolism (see p. 418). Folate deficiency is relatively common, and leads to disturbances in nucleotide biosynthesis and thus cell proliferation. As the precursors for blood cells divide particularly rapidly, disturbances of the blood picture can occur, with increased amounts of abnormal precursors for megalocytes megaloblastic anemia). Later, general damage ensues as phospholipid... 

Folic acid derivatives folate, 7,8-dihydrofolate, Bu N--l>0< Me0H-H,0 (35 65) Ocnidccyl 238... 

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]. 

The compound sulfanilamide exhibits a structural similarity to para-amino benzoic acid (PABA). Woods and Fields proposed the theory that sulfonamides, being structurally similar to PABA, inhibit bacterial folate synthetase so that folic acid is not formed which is needed for a number of metabolic reactions. Folic acid derived from PABA is essential for bacterial metabolism. Sulfonamides inhibit the enzyme folic acid synthetase which is... 

Folic acid and its polyglutamyl derivatives can be reduced to the THF coenzymes in two stages the first step is a slow reduction with NADPH to 7,8-dihydro-folate (step a, Fig. 15-18). The same enzyme that catalyzes this reaction rapidly reduces the dihydrofolates... 

Although the terms folic acid and folate are often used interchangeably, correctly/ofic acid refers to the oxidized compound, pteroyl monoglutamate, and the various tetrahydrofolate derivatives are collectively known as folates. 

The folate in foods consists of a mixture of the different one-carbon substituted derivatives, with varying numbers of conjugated glutamyl residues. The biological availability of these vitamers differs and is consistently lower than that of free folic acid (pteroyl monoglutamate), which is the compound that... 

The enzyme dihydrofolic acid (DHF) S5mthase (see below) converts p-aminobenzoic acid (PABA) to DHF which is subsequently converted to tetrahydric folic acid (THF), purines and DNA. The sulphonamides are structurally similar to PABA, successfully compete with it for DHF s)mthase and thus ultimately impair DNA formation. Most bacteria do not use preformed folate, but humans derive DHF from dietary folate which protects their cells from the metabolic effect of sulphonamides. Trimethoprim acts at the subsequent step by inhibiting DHF reductase, which converts DHF to THF. The drug is relatively safe because bacterial DHF reductase is much more sensitive to trimethoprim than is the human form of the enzyme. Both sulphonamides and trimethoprim are bacteriostatic. 

Vitamin M Vitamin M is also called pteroylglutaminic add or folic acid. It was isolated from yeast extract by Wills in 1930. Its structure was described by Anger in 1946. Folic add is made up of pteridine + p-aminobenzoic add + glutamic add. There are several known derivatives, called folates, which are capable of mutual restructuring. The coenzyme tetrahydrofolic acid, which plays a role in many biochemical reactions, is formed with the help of Bi2. Around 50% of total body folate are stored in the liver. A folate-binding protein (FBP) is available for transport. Folate undergoes enterohepatic circulation. The release of folate from the liver cells is stimulated by alcohol, which increases urine excretion. Folate deficiency (e.g. in the case of alcohol abuse) is accompanied by the development of macrocytosis. 

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