Folates chemical structures

Methotrexate (MTX, chemical structure shown in Fig. 1.) competitively inhibits the dehyrofolate reductase, an enzyme that plays an essential role in purine synthesis. The dehydrofolate reductase regenerates reduced folates when thymidine monophosphate is formed from deoxyuridine monophosphate. Without reduced folates cells are unable to synthesize thymine. Administration of N-5 tetrahydrofolate or N-5 formyl-tetrahydrofolate (folinic acid) can bypass this block and rescue cells from methotrexate activity by serving as antidote. 

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). 

Figure 14.2 Chemical structure of folates. Folate molecules consist of pteridine, para-aminobenzoate (pABA), and glutamate moieties. Plants usually contain polyglutamylated forms of folates that are made by the addition of up to about six glutamate residues (which form the y-glutamate tail) attached to the first glutamate, each linked by amide bonds to the preceding molecule of glutamate through the y-carboxyl of the latter. Cl units at various levels of oxidation can be attached to NS and/or N1 0, as indicated by Ri and R2.

Vtamin A supplementation, 564-565 Vitamin B(, 493, 541-542 aminotranK/ei ase, 209 assessmenl of status, 546-550 biochcinistry, 542-545 cardiovascular disease and, 553 homocysteine and, 550-554 homocysbnuria, 550,554 toxidty, 550 water solubility, 27 Vitamin Bs deficiency, 545-546 Vitamin supplements, 551 Vitamin Bu, 493,507, 516 absorption, 81-82 assessment of status, 522-524 biocbemistry, 516-517 chemical structure, 517 Cobalt and, 4t homocystBine and, 553 Vitamin Bij dehdency, 517-524 causes of, 518-522 elderly population, 521,553 folate deficiency and, 507, 511-312, 518 hematologic signs, 513... 

Fig. 6 The chemical structure of folic acid and the series of distinct steps of the folate receptor-mediated endocytosis (adapted from Ref. [187] with permission)...

Chemical structure (Figure 10). Pteroylglutamic (PteGlu) is composed of a pterin moiety, 4-amino-benzoic acid and glutamic acid and is the parent substance numerous folates . 

Figure 29.1 Chemical structure of folate (folic acid).

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

Folates exist in many chemical forms. The coenzyme form that functions in accepting one-carbon groups is tetrahydrofolate polyglutamate (Fig. 40.2), generally just referred to as tetrahydrofolate or FH4. It has three major structural components, a bicyclic pteridine ring, para-aminobenzoic acid, and a polyglutamate tail consisting... 

Elucidation of the structure of the B vitamins resxilted in the development of analytical chemical methods. Such methods are useful in industries manufacturing vitamins in which measurements of microgram to milligram quantities are routine, but these same methods are often not applicable to biological fiuids that contain as little as picogram quantities. Colorimetric and fluorometric techniques have been developed for niacin and folate, but these techniques require complicated extraction procedures and blank determinations. They also suflFer from lack of specificity, and the results are often altered by interference from biologically inactive materials that occur naturally or are produced during extraction (16,20). 

Miller, G.H., Doukas, P.H. and Seydel, J.K. 1972. Sulfonamide structure-activity relationship in a cell-free system. Correlation of inhibition of folate synthesis with antibacterial activity and physico-chemical parameters. J. Med. Chem. 15 700-706. 

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