Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Folate utilization

Folate antagonists (eg, methotrexate and certain antiepileptics) are used ia treatment for various diseases, but their adininistration can lead to a functional folate deficiency. Folate utilization can be impaired by a depletion of ziac (see Zinc compounds). In humans, the intestinal bmsh border folate conjugase is a ziac metaHoenzyme (72). One study iadicates that the substantial consumption of alcohol, when combiaed with an iaadequate iatake of folate and methionine, may iacrease the risk of colon cancer (73). Based on this study, it is recommended to avoid excess alcohol consumption and iacrease folate iatake to lower the risk of colon cancer. [Pg.42]

There is another fundamental difference between folate utilization in microbial and mammalian cells. Bacteria and protozoa are unable to take up exogenous folate and must synthesize it themselves. This is carried out in a series of reactions involving first the synthesis of dihydropteroic acid from one molecule each of pteridine and p-aminobenzoic acid (PABA). Glutamic acid is then added to form DHF which is reduced by DHFR to THF. Mammalian cells do not make their own DHF, instead they take it up firm dietary nutrients and convert it to THF using DHFR. [Pg.176]

There is another fundamental difference between folate utilization in microbial and mammalian cells (Fig. 12.7). Bacteria and protozoa are unable to... [Pg.216]

Wang, P., Read, M., Sims, P. F., and Hyde, J. E. (1997). Sulfadoxine resistance in the human malaria parasite Plasmodium falciparum is determined by mutations in dihydropteroate synthetase and an additional factor associated with folate utilization. Mol. Microbiol. 23, 979-986. [Pg.389]

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). [Pg.50]

Figure 45-16. Sources and utilization of one-carbon substituted folates. Figure 45-16. Sources and utilization of one-carbon substituted folates.
The enzyme mediating remethylation, 5-methyltetrahy-drofolate-betaine methyltransferase (Fig. 40-4 reaction 4), utilizes methylcobalamin as a cofactor. The kinetics of the reaction favor remethylation. Faulty remethylation can occur secondary to (1) dietary factors, e.g. vitamin B12 deficiency (2) a congenital absence of the apoenzyme (3) a congenital inability to convert folate or B12 to the methylated, metabolically active form (see below) or (4) the presence of a metabolic inhibitor, e.g. an antifolate agent that is used in an antineoplastic regimen. [Pg.675]

A similar set of conditions was utilized by Reif et al.76 to analyze folic acid, using leucovorin as an internal standard. Other authors77 have used similar conditions to study extensively the identity of possible leucovorin contaminants. In addition to these partition /ionization surpression methods, anion exchange hplc has been used to separate CF from other naturally occurring folates,78 and some correlation has been made between the number of glutamyl residues and retention time. [Pg.343]

Glycinamide ribonucleotide transformylase (GAR Tfase) is a folate-dependent enzyme essential to the de novo purine biosynthetic pathway. It utilizes the cofactor 10-formyl tetrahydrofohc acid (10-formyl-THF) to transfer a formyl group to the primary amine of its substrate a-glycinamide ribonucleotide. Potent, and potentially selective, inhibitors of GARTfase and de novo purine biosynthesis have been shown to be promising as antitumor drugs. [Pg.253]

L-Tetrahydrofolic acid is a versatile intermediate for the manufacture of various folates, e.g., L-leucovorin [19], which is used in cancer therapy, or Metafolin , which is used as a vitamin in functional food. To our knowledge optically pure L-tetrahydrofolic acid is still obtained by repeated fractional crystallization from an equimolar mixture of diastereoisomers formed by nondiastereoselective hydrogenation of folic acid. In order to increase the yield of l-tetrahydrofolic acid and to avoid recrystallization steps, we checked the utility of our ligand for the diastereoselective hydrogenation of folic acid dimethyl ester benzenesulfonate (Scheme 1.4.4). [Pg.122]

Aromatic compounds arise in several ways. The major mute utilized by autotrophic organisms for synthesis of the aromatic amino acids, quinones, and tocopherols is the shikimate pathway. As outlined here, it starts with the glycolysis intermediate phosphoenolpyruvate (PEP) and erythrose 4-phosphate, a metabolite from the pentose phosphate pathway. Phenylalanine, tyrosine, and tryptophan are not only used for protein synthesis but are converted into a broad range of hormones, chromophores, alkaloids, and structural materials. In plants phenylalanine is deaminated to cinnamate which yields hundreds of secondary products. In another pathway ribose 5-phosphate is converted to pyrimidine and purine nucleotides and also to flavins, folates, molybdopterin, and many other pterin derivatives. [Pg.1420]

Methylation of dUMP to give thymidylate is catalyzed by thymidylate synthase and utilizes 5,10-methylenetetra-hydrofolate as the source of the methyl group. This reaction is unique in the metabolism of folate derivatives because the folate derivative acts both as a donor of the one-carbon group and as its reductant, using the reduced pteridine ring as the source of reducing potential. Consequently, in this reaction, unlike any other in folate metabolism, dihydrofolate is a product (fig. 23.16). Since folate derivatives are present in cells at very low concentrations, continued syn-... [Pg.546]

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. [Pg.102]

Tetrahydrofolate cofactors participate in one-carbon transfer reactions. As described above in the section on vitamin B12, one of these essential reactions produces the dTMP needed for DNA synthesis. In this reaction, the enzyme thymidylate synthase catalyzes the transfer of the one-carbon unit of N 5,N 10-methylenetetrahydrofolate to deoxyuridine monophosphate (dUMP) to form dTMP (Figure 33-2, reaction 2). Unlike all of the other enzymatic reactions that utilize folate cofactors, in this reaction the cofactor is oxidized to dihydrofolate, and for each mole of dTMP produced, one mole of tetrahydrofolate is consumed. In rapidly proliferating tissues, considerable amounts of tetrahydrofolate can be consumed in this reaction, and continued DNA synthesis requires continued regeneration of tetrahydrofolate by reduction of dihydrofolate, catalyzed by the enzyme dihydrofolate reductase. The tetrahydrofolate thus produced can then reform the cofactor N 5,N 10-methylenetetrahydrofolate by the action of serine transhydroxy- methylase and thus allow for the continued synthesis of dTMP. The combined catalytic activities of dTMP synthase, dihydrofolate reductase, and serine transhydroxymethylase are often referred to as the dTMP synthesis cycle. Enzymes in the dTMP cycle are the targets of two anticancer drugs methotrexate inhibits dihydrofolate reductase, and a metabolite of 5-fluorouracil inhibits thymidylate synthase (see Chapter 55 Cancer Chemotherapy). [Pg.750]

However, lack of utilization of exogenous folate may not fully explain the apparently indispensable nature of the synthesis of 7,8-dihydropteroate in plasmodium, toxoplasma, and eimeria. It is known that most of the folate molecules in mammalian cells are linked with polyglutamates in the cytoplasm and are transported across cell membranes with difficulty. It may compound the problem of obtaining 7,8-dihydropteroate or dihydrofolate for the parasite and makes all of the enzymes... [Pg.1192]

Most of the dietary folate undergoes reduction and methylation within the intestinalmucosa and what enters theportal bloodstream is alargely 5-methyl-tetrahydrofolate. Single doses of more than about 200 /xg of folic acid saturate the intestinal dUiydrofolate reductase, so that free folic acid is absorbed and circulates in the bloodstream. It can be taken up by tissues, reduced to tetrahy-drofolate, and utilized. [Pg.274]

Methylene-Tetrahydrofolate Reductase The reduction of methylene-tetrahydrofolate to methyl-tetrahydrofolate, shown in Figure 10.7, is catalyzed hy methylene-tetrahydrofolate reductase, a flavin adenine dinucleotide-dependent enzyme during the reaction, the pteridine ring of the substrate is oxidized to dihydrofolate, then reduced to tetrahydrofolate by the flavin, which is reduced by nicotinamide adenine dinucleotide phosphate (NADPH Matthews and Daubner, 1982). The reaction is irreversible under physiological conditions, and methyl-tetrahydrofolate - which is the main form of folate taken up into tissues (Section 10.2.2) - can only be utilized after demethylation catalyzed by methionine synthetase (Section 10.3.4). [Pg.284]

Unlike most enzymes utilizing or metabolizing tetrahydrofolate, methionine synthetase has equal activity toward methyl-tetrahydrofolate mono- and polyglutamates. As discussed in Section 10.2.2, demethylation of methyl-tetrahydrofolate is essendal for the polyglutamylation and intracellular accumulation of folate. [Pg.291]


See other pages where Folate utilization is mentioned: [Pg.56]    [Pg.740]    [Pg.750]    [Pg.727]    [Pg.275]    [Pg.275]    [Pg.275]    [Pg.281]    [Pg.282]    [Pg.51]    [Pg.377]    [Pg.377]    [Pg.4924]    [Pg.56]    [Pg.740]    [Pg.750]    [Pg.727]    [Pg.275]    [Pg.275]    [Pg.275]    [Pg.281]    [Pg.282]    [Pg.51]    [Pg.377]    [Pg.377]    [Pg.4924]    [Pg.274]    [Pg.437]    [Pg.253]    [Pg.376]    [Pg.341]    [Pg.93]    [Pg.272]    [Pg.805]    [Pg.185]    [Pg.456]    [Pg.182]    [Pg.150]    [Pg.142]    [Pg.310]    [Pg.274]    [Pg.278]    [Pg.286]   
See also in sourсe #XX -- [ Pg.176 ]




SEARCH



Utilization of One-Carbon Substituted Folates

© 2024 chempedia.info