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)

As many as one-third of mutations in a gene result in the corresponding enzyme having an increased Michaelis constant, or K(m), (decreased binding affinity) for a coenzyme, resulting in a lower rate of reaction. About 50 human genetic dis-eases due to defective enzymes can be remedied or ameliorated by the administration of high doses of the vitamin component of the corresponding coenzyme, which at least partially restores enzymatic activity. Several single-nucleotide polymorphisms, in which the variant amino acid reduces coenzyme binding and thus enzymatic activity, are likely to be remediable by raising cellular concentrations of the cofactor through high-dose vitamin therapy. Some examples include the alanine-to-valine substitution at codon 222 (Ala222-->Val) [DNA: C-to-T substitution at nucleo-tide 677 (677C-->T)] in methylenetetrahydrofolate reductase (NADPH) and the cofactor FAD (in relation to cardiovascular disease, migraines, and rages), the Pro187-->Ser (DNA: 609C-->T) mutation in NAD(P):quinone oxidoreductase 1 [NAD(P)H dehy-drogenase (quinone)] and FAD (in relation to cancer), the Ala44-->Gly (DNA: 131C-->G) mutation in glucose-6-phosphate 1-dehydrogenase and NADP (in relation to favism and hemolytic anemia), and the Glu487-->Lys mutation (present in one-half of Asians) in aldehyde dehydrogenase (NAD + ) and NAD (in relation to alcohol intolerance, Alzheimer disease, and cancer).
 ...
PMID:High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms. 1191 49

A modestly elevated total plasma homocysteine concentration (tHcy) is generally accepted as an independent and graded risk factor for various pathologies, including vascular diseases, neural tube defects, Alzheimer disease, and pregnancy complications. We analyzed 5 common functional polymorphisms in enzymes involved in homocysteine metabolism (ie, methylenetetrahydrofolate reductase [MTHFR] 677C>T and 1298A>C, methionine synthase [MTR] 2756A>G, cystathionine beta-synthase [CBS] 844ins68, and methionine synthase reductase [MTRR] 66A>G) in 452 young adults, and quantified their independent and interactive effects on tHcy concentrations. Serum folate, red cell folate, vitamin B(12), and tHcy concentrations were significantly influenced by MTHFR 677C>T genotypes. A particularly strong interaction was observed between the MTHFR 677TT genotype and serum folate, which led to a high tHcy phenotype that was more pronounced in males. The genetic contribution to the variance in tHcy was estimated to be approximately 9%, compared with approximately 35% that could be attributed to low folate and vitamin B(12). Our study indicates that dietary factors are centrally important in the control of tHcy levels in young adults with additional, but somewhat weaker, genetic effects. These data underscore the potential benefits that may be gained by improving the dietary status of young adults, and provide support for the implementation of folate/B-vitamin food fortification programs.
 ...
PMID:Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults. 1264 43

The establishment of medical genomics in Mexico offers the possibility to study in a more comprehensive manner the etiological factors of different diseases, providing a global view of the interaction between the genome and the environment. Nutrition is recognized as a significant determinant in several diseases, yet its interaction with polymorphisms, and in general with the genome, has not been properly addressed Mexico has a high prevalence of polymorphisms of the methylenetetrahydrofolate reductase gene, and in both clinical and basic studies this has been associated with an increased susceptibility of developing Alzheimer's disease. We propose a potential nutrigenomic approach for the study of Alzheimer disease in Mexico.
 ...
PMID:[Alzheimer's disease and methylenetetrahydrofolate reductase gene polymorphisms: a potential nutrigenomic approach for Mexico]. 1951 22