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)

Extracts of human normal and leukemic leukocytes contain an enzyme that catalyzes a transfer of labeled methyl carbon from N5-[14C]methyltetrahydrofolate to tryptamine. Evidence is presented that this reaction is not attributable to a methyltransferase but to the following reaction sequence: (a) an oxidation of N5-[14C]methyltetrahydrofolate to N5, N10-[14C]methylenetetrahydrofolate that is catalyzed by N5, N10-methylenetetrahydrofolate reductase (EC 1.1.1.68); (b) spontaneous release of [14C]formaldehyde from N5, N10-[14C]methylenetetrahydrofolate; and (c) nonenzymatic condensation of [14C]formaldehyde with tryptamine to form a radioactive carboline derivative. The occurrence of this sequence in leukocytes is suggested by data that show that the enzyme reaction is strongly stimulated by addition of flavin adenine dinucleotide and that the final product is chromatographically identical to the adduct formed in the reaction of [14C]formaldehyde with tryptamine. In the absence of tryptamine, a product accumulates that can react with other HCHO acceptors, i.e., beta-phenylethylamine and dimedone; another reaction product is tetrahydrofolate. Production of formaldehyde is relatively more active in normal lymphocytes than in normal granulocytes, but it is even higher in lymphocytes of chronic lymphocytic leukemia. Activity in granulocytes from a subject with chronic myelocytic leukemia is also elevated but to a lesser extent than activity in lymphocytes of chronic lymphocytic leukemia. Activity in granulocytes from a subject with chronic myelocytic leukemia is also elevated but to a lesser extent than activity in lymphocytes of chronic lymphocytic leukemia. Formaldehyde production in leukocytes is only slightly stimulated by addition of various cobalamins, and activity is normal in leukocytes from a vitamin B12-deficient patient. We conclude that the system is cobalamin independent. Thus, there exists an active pathway from N5-methyltetrahydrofolate to tetrahydrofolate other than the one catalyzed by cobalamin-dependent N5-methyltetrahydrofolate-homocysteine methyltransferase.
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PMID:Production of formaldehyde from N5-methyltetrahydrofolate by normal and leukemic leukocytes. 1 82

In the presence of 5-methoxytryptamine (5-MeOT), 5-methyltetrahydrofolic acid (5-MTHF) yields 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-MeOTHbetaC) in rat brain extracts, possibly via formaldehyde formation catalyzed by methylenetetrahydrofolate reductase. The formation of 6-MeOTHbetaC in selected brain regions, ranging from 452 +/- 40 pmol formed per mg protein per hour in corpus striatum to 119 +/- 17 pmol in cingulate cortex, is significantly correlated with the regional distribution of 1,2,3,4-tetrahydro-beta-carboline (THbetaC) formed from 5-MTHF and tryptamine (r = 0.76, p less than 0.01) as well as that of methylene-beta-phenylethylimine (MbetaphiEI) from 5-MTHF and beta-phenylethylamine (betaphiEA; r = 0.90, p less than 0.01). FAD enhances the activity, lowering both Vmax and Km values with respect to 5-MeOT and Vmax, but not Km, with respect to 5-MTHF.
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PMID:Regional formation of 6-methoxy-1,2,3,4-tetrahydro-beta-carboline in rat brain extract. 119 18

Biochemical and morphologic studies on a patient with homocystinuria due to a deficiency of 5, 10-methylenetetrahydrofolate reductase (EC. 1.1.1.68) were performed. The concentrations of homocystine in the patient's plasma and urine were 2.97 mumol/dl and 44.67 mumol/24 hr, respectively. Activities of 5, 10-methylenetetrahydrofolate reductase (expressed as nanomoles of formaldehyde formed per hr per mg of protein) in cultured skin fibroblasts and liver tissue were 0.53 (control: 5.14) and 0.00 (control: 13.80), respectively. The major abnormalities were found in the arterial bed, consisting of intimal hyperplasia, fragmentation, and disruption of elastic lamellae and subcellular changes in the endothelial cells. Extensive thrombosis was observed. The brain and the liver also showed widespread pathologic changes. In the former, neuronal loss and cellular damage were prominent and extensive. Diffuse demyelination with moderate astrocytosis was found; but demyelination was out of proportion to the vascular changes. Hirano bodies in the cortical neurons and crystalline and lamellar bodies in the Purkinje cells were observed. In the liver, there were fatty change and mild to moderate portal fibrosis. Bizarre, giant mitochondria and membrane-bound multivesicular bodies were found. Mild pathologic changes were also observed in the striated muscles and the kidneys. Focal fragmentation, disruption, and smearing of the Z discs and disorganization of the myofilaments were found in the skeletal muscles. The kidneys showed shrunken glomeruli, thickened basement membranes, and swelling of epithelial as well as endothelial cells.
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PMID:Morphologic studies in a patient with homocystinuria due to 5, 10-methylenetetrahydrofolate reductase deficiency. 127 36

Severe methylenetetrahydrofolate reductase (MTHFR) deficiency with less than 2% of normal enzyme activity is characterized by neurological abnormalities, atherosclerotic changes, and thromboembolism. We have discovered a "new" variant of MTHFR deficiency which is characterized by the absence of neurological abnormalities, an enzyme activity of about 50% of the normal value, and distinctive thermolability under specific conditions of heat inactivation. In this study, lymphocyte MTHFR specific activities in the thermolabile variant and control groups were 5.58 +/- 0.91 and 10.33 +/- 2.89 nmol formaldehyde formed/mg protein/h, respectively. The difference was significant (P less than .01). However, there was overlap among the individual values from the two groups. On the other hand, residual MTHFR activity after heat inactivation was 11.2 +/- 1.43% in the thermolabile variant and 36.3 +/- 5.18% in the controls. There was no overlap. Enzyme studies in 10 subjects with thermolabile MTHFR and their family members support the hypothesis that thermolabile MTHFR is inherited as an autosomal recessive trait. To elucidate the association of thermolabile MTHFR with the development of coronary artery disease, we determined the thermostability of lymphocyte MTHFR in 212 patients with proven coronary artery disease and in 202 controls without clinical evidence of atherosclerotic vascular disease. Thermolabile MTHFR was found in 36 (17.0%) cardiac patients and 10 (5.0%) controls. The difference in incidence between the two groups was statistically significant (P less than .01). The average age at onset of clinical coronary artery disease in 36 patients with thermolabile MTHFR was 57.3 +/- 7.6 years (35-72 years). The mean total plasma homocysteine concentration in patients with thermolabile MTHFR was 13.19 +/- 5.32 nmol/ml and was significantly different from the normal mean of 8.50 +/- 2.80 nmol/ml (P less than .05). There was no association between thermolabile MTHFR and other major risk factors. We conclude that thermolabile MTHFR is a variant(s) of MTHFR deficiency which is inherited as an autosomal recessive trait. In addition, it is positively associated with the development of coronary artery disease. Determination of in vitro thermostability of lymphocyte MTHFR is a reliable method for identifying subjects with this abnormality.
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PMID:Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease. 199 39

The specific activities of four folate enzymes have been measured in livers from preterm infants (Group 1), full-term infants (Group 2), and from control subjects (Group 3). The four enzymes studied were methylene tetrahydrofolate reductase (EC 1.1.1.68), methionine synthetase (EC 2.1.1.13), methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5), and glutamate formiminotransferase (EC 2.1.2.5). The specific activities for methylenetetrahydrofolate reductase were 6.62 +/- 0.51, 4.42 +/- 0.31, and 2.60 +/- 0.40 (nmoles formaldehyde/mg protein/h, mean +/- S.E.) for groups 1, 2 and 3, respectively. The specific activities for the three groups for methionine synthetase were 0.99 +/0 0.11, 0.64 +/- 0.06, and 0.42 +/- 0.05 (nmoles methionine/mg protein/h), mean +/- S.E.). The specific activities for the three groups for glutamine formiminotransferase were 84.1 +/-10.7, 108.6 +/-14.6, and 104.3 +/- 17.8 (nmoles methenyltetrahydrofolate/mg protein/min, mean +/- S.E.). The specific activities for the three groups for methylenetetrahydrofolate dehydrogenase were 0.16 +/- 0.03, 0.39 +/- 0.07, and 0.92 +/- 0.16 (nmoles methenyltetrahydrofolate/mg protein/min, mean +/- S.E.). During development, the specific activities of methylenetetrahydrofolate reductase and methionine synthetase decreased whereas the specific activity of methylenetetrahydrofolate dehydrogenase increased and that of glutamate formiminotransferase remained constant. In addition, the activities of methylenetetrahydrofolate reductase, methionine synthetase, and methylenetetrahydrofolate dehydrogenase were significantly influenced by postnatal age.
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PMID:Differences in liver folate enzyme patterns in premature and full term infants. 705 Aug 70

Methylenetetrahydrofolate reductase catalyzes the reduction of N(5), N(10)-methylenetetrahydrofolate to N(5)-methyltetrahydrofolate. Because this substrate is unstable and dissociates spontaneously into formaldehyde and tetrahydrofolate, the customary method to assay the catalytic activity of this enzyme has been to measure the oxidation of [14C]N(5)-methyltetrahydrofolate to N(5), N(10)-methylenetetrahydrofolate and quantify the [14C]formaldehyde that dissociates from this product. This report describes a very sensitive radioenzymatic assay that measures directly the reductive catalysis of N(5),N(10)-methylenetetrahydrofolate. The radio-labeled substrate, [14C]N(5),N(10)-methylenetetrahydrofolate, is prepared by condensation of [C(14)]formaldehyde with tetrahydrofolate and the stability of this substrate is maintained for several months by storage at -80 degrees C in a pH 9.5 buffer. Partially purified methylenetetrahydrofolate reductase from rat liver, incubated with the radio-labeled substrate and the cofactors, NADPH and FAD at pH 7. 5, generates [14C]N(5)-methyltetrahydrofolate, which is stable and partitions into the aqueous phase after the assay is terminated with dimedone and toluene. A K(m) value of 8.2 microM was obtained under conditions of increasing substrate concentration to ensure saturation kinetics. This method is simple, very sensitive and measures directly the reduction of N(5), N(10)-methylenetetrahydrofolate to N(5)-methyltetrahydrofolate, which is the physiologic catalytic pathway for methylenetetrahydrofolate reductase.
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PMID:Radioenzymatic assay for reductive catalysis of N(5)N(10)-methylenetetrahydrofolate by methylenetetrahydrofolate reductase. 1108 90