Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A greater number of inherited metabolic disorders can now be treated with special diets or cofactors. Recent progress is illustrated by the example of various hyperphenylalaninaemias (HPHE), of maple syrup urine disease (MSUD) and of various homocystinurias (HCY). Of special importance for the future is a severe embryopathy in infants of mothers with HPHE and its possible prevention by reintroducing a phenylalanine - restricted diet for the mother before conception. Of considerable scientific interest and therapeutic impact is also the treatment of patients with HPHE due to tetrahydrobiopterin deficiency. This consists in substituting the patients' metabolism with this cofactor of phenylalanine hydroxylase as well as with neurotransmitters. Cofactor deficiencies have also been described in MSUD and HCY, and substitution with high doses of thiamine and pyridoxin has been successful. The management of the acute metabolic derangement of neonatal MSUD is a great therapeutic challenge even to experienced metabolic centres. Rational therapy for homocystinurias due to remethylation defects is still being explored. In siblings with methylenetetrahydrofolate reductase deficiency we used leucovorin for the first time and with success.
 ...
PMID:[Diet therapy and coenzyme therapy in hereditary metabolic diseases]. 613 9

Pig liver methylenetetrahydrofolate reductase catalyzes the reduction of quinonoid dihydropterins in vitro. Either NADPH or methyltetrahydrofolate can serve as the electron donor. Methylenetetrahydrofolate reductase can also suppor phenylalanine hydroxylation in vitro by regeneration of the tetrahydropterin cofactor. These results lend support to the proposal that reduction of methylenetetrahydrofolate proceeds by tautomerization of the 5-iminium cation to form quinonoid 5-methyldihydrofolate, which is then reduced to methyltetrahydrofolate (Matthews, R. G., and Haywood, B. J. (1979) Biochemistry 18, 4845-4851). Under Vmax conditions, the turnover numbers for the NADPH-linked reductions of the quinonoid forms of 6,7-dimethyldihydropterin, dihydrobiopterin, and dihydrofolate are all about the same as that for the reduction of methylenetetrahydrofolate. The Km values for racemic mixtures of the same quinonoid acceptors are 40, 30, and 20 microM, respectively, while the Km for (6R,S)methylenetetrahydrofolate is 20 microM at pH 7.2 in phosphate buffer. The reduction of quinonoid dihydropterins is inhibited by adenosylmethionine and dihydropteroylhexaglutamate, which are known to modulate methylenetretrahydrofolate reductase activity.
 ...
PMID:Characterization of the dihydropterin reductase activity of pig liver methylenetetrahydrofolate reductase. 696 65

Drought is a major abiotic stress affecting all levels of plant organization and, in particular, leaf elongation. Several experiments were designed to study the effect of water deficits on maize (Zea mays) leaves at the protein level by taking into account the reduction of leaf elongation. Proteomic analyses of growing maize leaves allowed us to show that two isoforms of caffeic acid/5-hydroxyferulic 3-O-methyltransferase (COMT) accumulated mostly at 10 to 20 cm from the leaf point of insertion and that drought resulted in a shift of this region of maximal accumulation toward basal regions. We showed that this shift was due to the combined effect of reductions in growth and in total amounts of COMT. Several other enzymes involved in lignin and/or flavonoid synthesis (caffeoyl-CoA 3-O-methyltransferase, phenylalanine ammonia lyase, methylenetetrahydrofolate reductase, and several isoforms of S-adenosyl-l-methionine synthase and methionine synthase) were highly correlated with COMT, reinforcing the hypothesis that the zone of maximal accumulation corresponds to a zone of lignification. According to the accumulation profiles of the enzymes, lignification increases in leaves of control plants when their growth decreases before reaching their final size. Lignin levels analyzed by thioacidolysis confirmed that lignin is synthesized in the region where we observed the maximal accumulation of these enzymes. Consistent with the levels of these enzymes, we found that the lignin level was lower in leaves of plants subjected to water deficit than in those of well-watered plants.
 ...
PMID:Water deficits affect caffeate O-methyltransferase, lignification, and related enzymes in maize leaves. A proteomic investigation. 1572 45