Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The concentrations of folate-dependent enzymes in Neurospora crassa Lindegren A wild type (FGSC no. 853), Ser-l mutant, strain H605a (FGSC no. 118), and for mutant, strain C-24 (FGSC no. 9), were compared during exponential growth on defined minimal media. Both mutants were partially lacking in serine hydroxymethyltransferase, but contained higher concentrations of 10-formyltetrahydrofolate synthetase than did the wild type. Mycelia of the mutants contained higher concentrations of these enzymes when growth media were supplemented with 1mM-glycine. In the wild-type, this glycine supplement also increased the specific activities of 5,10-methylenetetrahydrofolate dehydrogenase and 5,10-methylenetetrahydrofolate reductase. 5. During growth, total folate and polyglutamyl folate concentrations were greatest in the wild-type. Methylfolates were not detected in mutant Ser-l, and were only present in the for mutant after growth in glycine-supplemented media. Exogenous glycine increased folate concentration threefold in the wild type, mainly owing to increases in unsubstituted polyglutamyl derivatives. 3. Feeding experiments using 14C-labelled substrates showed that C1 units were generated from formate, glycine and serine in the wild type. Greater incorporation of 14C occurred when mycelia were cultured in glycine-supplemented media. Formate and serine were precursors of C1 units in the mutants, but the ability to cleave glycine was slight or lacking.
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PMID:One-carbon metabolism in Neurospora crassa wild-type and in mutants partially deficient in serine hydroxymethyltransferase. 13 22

1. The concentrations of folate derivatives in aerobic cultures of Saccharomyces cerevisiae (A.T.C.C. 9763) were determined by microbiological assay employing Lactobacillus casei (A.T.C.C. 7469) and Pediococcus cerevisiae (A.T.C.C. 8081). Cells cultured in media lacking l-methionine contained higher concentrations of folate derivatives than cells grown in the same media supplemented with 2.5mumol of l-methionine/ml. The concentrations of highly conjugated derivatives were also decreased by supplementing the growth medium with l-methionine. 2. DEAE-cellulose column chromatography of extracts prepared from cells grown under these conditions revealed that the concentrations of methylated tetrahydrofolates were drastically decreased by the methionine supplement. Smaller decreases were also observed in the concentrations of formylated and unsubstituted derivatives. 3. The concentrations of four enzymes of C(1) metabolism were compared after 6h of growth in the presence and in the absence of l-methionine (2.5mumol/ml). The specific activities of formyltetrahydrofolate synthetase, methylenetetrahydrofolate reductase and serine hydroxymethyltransferase were not altered by this treatment but that of 5-methyltetrahydrofolate-homocysteine methyltransferase was decreased by approx. 65% when l-methionine was supplied. The activities of 5-methyltetrahydrofolate-homocysteine methyltransferase, serine hydroxymethyltransferase and formyltetrahydrofolate synthetase were not appreciably altered by l-methionine in vitro. In contrast this amino acid was found to inhibit the activity of methylenetetrahydrofolate reductase. 4. Feeding experiments employing sodium [(14)C]formate indicated that cells grown in the presence of exogenous methionine, although having less ability to convert formate into methionine, readily incorporated (14)C into serine and the adenosyl moiety of S-adenosylmethionine. 5. It is suggested that exogenous l-methionine controls C(1) metabolism in Saccharomyces principally by regulation of methyl-group biogenesis within the folate pool.
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PMID:Regulation of C metabolism by L-methionine in Saccharomyces cerevisiae. 419 57

Clostridium thermoaceticum ferments xylose, fructose, and glucose with acetate as the only product. In fermentations with mixtures of the sugars, xylose is first fermented, then fructose, and last, glucose. Fructose inhibits the fermentation of glucose, and this inhibition appears to be due to a repression of the synthesis of an enzyme needed for glucose utilization. Addition of metals to the culture medium increases the cell yield drastically from about 7 to 18 g per liter, and Y(glucose) values between 40 and 50 are obtained. According to the postulated pathways of the fermentation of glucose and synthesis of acetate from CO(2) by C. thermoaceticum, 3 mol of ATP are available as energy for growth. Thus a Y(adenosine 5'-triphosphate) of 13 to 16 is obtained. Because the normal Y(ATP) value is 10.5, this could mean that an additional source of ATP is available by an unknown mechanism. The addition of metals also increases the nicotinamide adenine dinucleotide phosphate-dependent formate dehydrogenase activity, the overall reaction ((14)CO(2) --> acetate), and the incorporation of the methyl group of 5-methyltetrahydrofolate into acetate. These reactions are catalyzed very efficiently by cells harvested in early growth, whereas cells obtained at the end of a fermentation have very low formate dehydrogenase activity and capacity to incorporate CO(2) into acetate. The following enzymes involved in the synthesis of acetate from CO(2) and in the metabolism of pyruvate are present in extracts of C. thermoaceticum: 10-formyltetrahydrofolate synthetase, 5,10-methenyltetrahydrofolate cyclohydrolase, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methylenetetrahydrofolate reductase, phosphate acetyltransferase, and acetate kinase. These enzymes are not or are very little affected by the addition of metals to the growth medium. The amount of corrinoids in cells from early growth is low, whereas it is high in cells harvested late in growth. The opposite is found for the activity of delta-aminolevulinate dehydratase, which is high at the beginning of growth and low at the end.
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PMID:Fermentation of glucose, fructose, and xylose by Clostridium thermoaceticum: effect of metals on growth yield, enzymes, and the synthesis of acetate from CO 2 . 470 93

Clostridium formicoaceticum ferments fructose labeled with (14)C in carbon 1, 4, 5, or 6 via the Embden Meyerhof pathway. In fermentations of fructose in the presence of (14)CO(2), acetate is formed labeled equally in both carbons. Extracts convert the methyl groups of 5-methyltetrahydrofolate and methyl-B(12) to the methyl group of acetate in the presence of pyruvate. Formate dehydrogenase, 10-formyltetrahydrofolate synthetase, 5,10-methenyltetrahydrofolate cyclohydrolase, 5,10-methylenetetrahydrofolate dehydrogenase, and 5,10-methylenetetrahydrofolate reductase are present in extracts of C. formicoaceticum. These enzymes are needed for the conversion of CO(2) to 5-methyltetrahydrofolate. It is proposed that acetate is totally synthesized from CO(2) via the reactions catalyzed by the enzymes listed above and that 5-methyltetra-hydrofolate and a methylcorrinoid are intermediates in this synthesis.
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PMID:Fermentation of fructose and synthesis of acetate from carbon dioxide by Clostridium formicoaceticum. 505 46

The activity of 4 enzymes involved in the formation and interconversion of folate coenzymes has been examined in liver and kidney of healthy and Ehrlich ascites carcinoma-bearing mice. In the liver, a 50% increase of methylenetetrahydrofolate reductase activity was shown soon after tumour cell inoculation, while the activity of formyltetrahydrofolate synthetase and methylenetetrahydrofolate dehydrogenase decrease by 20% at an advanced stage of tumour development. In kidneys of the host mouse the only change observed was a decrease of dihydrofolate reductase activity. The levels of activity of all assayed enzymes found in host organs were similar to that in Ehrlich carcinoma cells.
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PMID:Folate enzymes in Ehrlich ascites carcinoma-bearing mice. 639 50

Women who take folic acid periconceptionally reduce their risk of having a child with a neural tube defect (NTD) by >50%. A variant form of methylenetetrahydrofolate reductase (MTHFR) (677C-->T) is a known risk factor for NTDs, but the prevalence of the risk genotype explains only a small portion of the protective effect of folic acid. This has prompted the search for additional NTD-associated variants in folate-metabolism enzymes. We have analyzed five potential single-nucleotide polymorphisms (SNPs) in the cytoplasmic, nicotinamide adenine dinucleotide phosphate-dependent, trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase (MTHFD1) for an association with NTDs in the Irish population. One SNP, R653Q, in this gene appears to be associated with NTD risk. We observed an excess of the MTHFD1 "Q" allele in the mothers of children with NTD, compared with control individuals. This excess was driven by the overrepresentation of QQ homozygotes in the mothers of children with NTD compared with control individuals (odds ratio 1.52 [95% confidence interval 1.16-1.99], P=.003). We conclude that genetic variation in the MTHFD1 gene is associated with an increase in the genetically determined risk that a woman will bear a child with NTD and that the gene may be associated with decreased embryo survival.
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PMID:A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group. 1238 33

Mild hyperhomocysteinemia is a probable risk factor for atherosclerotic diseases and stroke. Recently, associations of elevated plasma homocysteine concentrations in the acute phase and of MTHFR 677 TT genotype with spontaneous cervical artery dissections (sCAD) have been reported. The purpose of this study was to test this hypothesis in the currently largest sample of patients with sCAD, taking into account known factors influencing plasma homocysteine levels. Ninety-five patients with past sCAD were compared with 95 age- and sex-matched healthy individuals. Homocysteine, vitamin B6, B12, folate, and polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T), cystathionine beta-synthase (CBS 844ins68bp) and methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase (MTHFD1 G1958A) were assessed and any associations were analysed using multivariate statistics. The occurrence of sCAD was associated with elevated homocysteine levels with an odds ratio of 1.327 per 20 % percentile. Homocysteine levels were influenced by gender, smoking status, occurrence of hypertension, vitamin B12 and folate levels, and by the MTHFR TT genotype. MTHFR, CBS 844ins68bp, and MTHFD1 G1958A genotype were not independently associated with the occurrence of sCAD. These data suggest that elevated homocysteine is associated with the occurrence of sCAD. The MTHFR C677T polymorphism is associated with the homocysteine level.
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PMID:Plasma homocysteine, MTHFR C677T, CBS 844ins68bp, and MTHFD1 G1958A polymorphisms in spontaneous cervical artery dissections. 1550 5

Low maternal folate or vitamin B12 status has been implicated in numerous pregnancy complications including spontaneous abortion. The primary aim of this study was to test a polymorphism within the trifunctional folate enzyme MTHFD1 (5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthetase) for an association with a mother's risk of having an unexplained second trimester pregnancy loss. We genotyped 125 women who had at least one unexplained spontaneous abortion or intrauterine fetal death between 13 and 26 weeks gestation and 625 control women with no history of prior pregnancy loss. Our study is the first to identify an association between the MTHFD1 1958G-->A (R653Q) polymorphism and the maternal risk of having an unexplained second trimester pregnancy loss. Women who are MTHFD1 1958AA homozygous have a 1.64-fold increased risk of having an unexplained second trimester loss compared to women who are MTHFD1 1958AG or 1958GG [OR 1.64 (1.05-2.57), P = 0.03]. It has been reported that polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR), 677C-->T (A222V), transcobalamin II (TCII), 776C-->G (P259R), are associated with pregnancy loss. Both variants were tested in this study. Neither showed evidence of significantly affecting the maternal risk of having a second trimester pregnancy loss. In conclusion, the MTHFD1 1958AA genotype may be an important maternal risk factor to consider during pregnancy.
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PMID:A polymorphism in the MTHFD1 gene increases a mother's risk of having an unexplained second trimester pregnancy loss. 1612 74

The aetiology of non-syndromic cleft lip with or without cleft palate (CL/P) is very complex. It has been shown that polymorphic variants of genes encoding key proteins of folate and methionine metabolism might be important maternal risk factors of having a child with this craniofacial anomaly. Therefore, in our study, mothers with CL/P children as well as control mothers were examined for prevalence of polymorphisms of genes that encode methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1) and reduced folate carrier 1 (RFC1). We observed that there were no statistical differences in allele and genotype frequencies of MTHFR c.677C>T, MTHFD1 c.1958G>A and RFC1 c.80G>A between mothers who had children with CL/P and control mothers. However, mothers with MTR c.2756AG or GG genotype displayed a 2.195-fold increased risk of having a child with CL/P (95% CI 1.189-4.050, p = 0.011). The mechanism by which polymorphic transition of MTR gene might increase the maternal risk of having CL/P progeny is unknown. Our observations are consistent with a significant role of the methyl cycle in the development of craniofacial structures in humans.
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PMID:Maternal MTR genotype contributes to the risk of non-syndromic cleft lip and palate in the Polish population. 1671 3

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by overexpression of cytokines and T cell accessory molecules, which is due to a reduction of DNA regulatory region methylation in T cells. It has been shown that polymorphic variants of genes encoding key enzymes of folate and methionine metabolism may have an effect on DNA methylation. Therefore, in patients with SLE (n = 106) and controls (n = 141) we examined the distribution of polymorphisms of genes encoding methionine synthase (MTR); 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1); and methylenetetrahydrofolate reductase (MTHFR). We found that MTR 2756AG (919DG) or GG (919GG) genotype exhibited 2.005-fold increased risk of SLE (95% CI = 1.177-3.416, P = 0.0146). However, MTHFR 677C > T (A222V) and MTHFD1 1958G > A (R653Q) allele and genotype frequencies did not exhibit statistical differences between SLE patients and controls. Since MTR is located on 1q43, our findings confirm the significance of the role of 1q region and the methyl cycle in etiopathogenesis of SLE.
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PMID:MTR 2756 A > G polymorphism is associated with the risk of systemic lupus erythematosus in the Polish population. 1766 38


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