Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification

@article{Goyette1994HumanMR,
  title={Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification},
  author={Philippe Goyette and James S. Sumner and Renate Milos and Alessandra M. V. Duncan and David S. Rosenblatt and Rowena G. Matthews and Rima Rozen},
  journal={Nature Genetics},
  year={1994},
  volume={7},
  pages={195-200}
}
Methylenetetrahydrofolate reductase (MTHFR) catalyses the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, a cofactor for homocysteine methylation to methionine. MTHFR deficiency, an autosomal recessive disorder, results in homocysteinemia. Using degenerate oligonucleotides based on porcine peptide sequence data, we isolated a 90–bp cDNA by PCR from pig liver RNA. This cDNA was used to isolate a human cDNA, the predicted amino acid sequence of which shows strong homology to… Expand
Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR)
TLDR
The isolation and characterization of the human and mouse genes for MTHFR are reported, finding the exon sizes, locations of intronic boundaries, and intron sizes are quite similar between the two species. Expand
Characterization of a pseudogene for murine methylenetetrahydrofolate reductase
TLDR
The structure of this paralogous gene and the identification of a repeat sequence at the 3′ end of this pseudogene suggest that it arose by retrotransposition of a mis-spliced Mthfr transcript. Expand
Methylenetetrahydrofolate Reductase: Comparison of the Enzyme from Mammalian and Bacterial Sources
Methylenetetrahydrofolate reductase catalyzes the reduction of methylenetetrahydrofolate to methyl-tetrahydrofolate, which serves as the methyl donor for the conversion of homocysteine to methionineExpand
Methylenetetrahydrofolate reductase and methionine synthase: biochemistry and molecular biology
TLDR
Structural/function studies on the bacterial proteins, summarized in this review, are relevant to the function of the human enzymes; in particular Studies on the effects of bacterial mutations analogous to those causing hyperhomocysteinemia in human may shed light on the defects associated with these mutations. Expand
Molecular phylogenetic analysis of methylenetetrahydrofolate reductase family of proteins.
TLDR
A previously unrecognized ATP synthase motif was found in all of the examined plant MTHFRs, suggesting a different functional capability to the plant M THFRs in addition to the known function. Expand
Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase
TLDR
The Ala222Val MTHFR, however, has an enhanced propensity to dissociate into monomers and to lose its FAD cofactor on dilution; the resulting loss of activity is slowed in the presence of methyltetrahydrofolate or adenosylmethionine. Expand
Methylenetetrahydrofolate reductase: a common human polymorphism and its biochemical implications.
TLDR
This review presents biochemical studies of a human polymorphism in methylenetetrahydrofolate reductase, which catalyzes the reaction shown below. Expand
Genomic structure and transcript variants of the human methylenetetrahydrofolate reductase gene
TLDR
The results of this study render the full-length characterisation of affected alleles in severe homocystinuria and moderate hyperhomocysteinaemia due to MTHFR deficiency and provide a basis for investigating the regulation of the human MTH FR gene. Expand
Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency
TLDR
The molecular basis of severe MTHFR deficiency in four unrelated families from Turkish/Greek ancestry is reported, and four novel mutations in the MTH FR gene are identified: two missense (983A→G; 1027T→G) and two nonsense (1084C→T; 1711C→ T) mutations. Expand
Functional characterization of missense mutations in severe methylenetetrahydrofolate reductase deficiency using a human expression system
TLDR
In vitro expression of 22 severe MTHFR missense mutations and two known single nucleotide polymorphisms is reported and decreased affinity for NADPH in individual mutant enzymes is confirmed, a result previously described in primary patient fibroblasts. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 22 REFERENCES
Methylenetetrahydrofolate reductase (MR) deficiency: thermolability of residual MR activity, methionine synthase activity, and methylcobalamin levels in cultured fibroblasts.
TLDR
Looking at MeCbl accumulation and MS activity in fibroblasts from 15 patients with MR deficiency found methyltetrahydrofolate levels were often lowest in the patients with early onset disease, and all but two patients had levels of methionine synthase within the control range. Expand
Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease.
TLDR
The thermostability of lymphocyte MTHFR is determined in 212 patients with proven coronary artery disease and in 202 controls without clinical evidence of atherosclerotic vascular disease and it is concluded that thermolabile MTHfr is a variant of MTH FR deficiency which is inherited as an autosomal recessive trait. Expand
Intermediate hyperhomocysteinemia resulting from compound heterozygosity of methylenetetrahydrofolate reductase mutations.
TLDR
Four subjects with thermolabile methylenetetrahydrofolate reductase (MTHFR) were discovered among 16 "obligate" heterozygotes for severe MTHFR deficiency and their family members and it is postulated that subjects with this genetic compound are more susceptible to the development of intermediate hyperhomocysteinemia despite normal folate and B12 levels. Expand
Nucleotide sequence of metF, the E. coli structural gene for 5-10 methylene tetrahydrofolate reductase and of its control region.
TLDR
The nucleotide sequence of the E.coli metF gene (888 nucleotides), coding for 5-10 methylene tetrahydrofolate reductase, has been determined and no structural evidence was found for an attenuation mechanism regulating the independent metF transcriptional unit. Expand
Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus
Deficiency of ornithine transcarbamylase (OTC; EC 2.1.3.3), a hepatic mitochondrial enzyme involved in the detoxification of ammonia1,2, is a severe inborn error of metabolism. It is an X-linkedExpand
Methylenetetrahydrofolate reductase from pig liver.
  • R. Matthews
  • Chemistry, Medicine
  • Methods in enzymology
  • 1986
TLDR
This chapter describes assay, purification, and properties of methylenetetrahydrofolate reductase from pig liver, which catalyzes the reaction which commits tetrahydofolate-bound one-carbon units to the pathway leading to homocysteine regeneration. Expand
Purification and characterization of methylenetetrahydrofolate reductase from human cadaver liver.
TLDR
It is suggested that human methylenetetrahydrofolate reductase is composed of two identical subunits of 75 kDa each but is cleaved into a major single band due to autolysis in cadaver liver. Expand
Purification and properties of methylenetetrahydrofolate reductase from pig liver.
TLDR
Methylenetetrahydrofolate reductase from pig liver has been purified to homogeneity, as judged by several criteria, and exhibits a typical flavoprotein absorption spectrum. Expand
Mammalian methylenetetrahydrofolate reductase. Partial purification, properties, and inhibition by S-adenosylmethionine.
TLDR
5,10-Methylenetetrahydrofolate reductase has been purified several hundred-fold from both rat and pig liver and exhibits a strong NADPH-specific diaphorase (reduced-NAD:lipoamide oxidoreductase, EC 1.6.4.2) activity. Expand
Symptomatic and asymptomatic methylenetetrahydrofolate reductase deficiency in two adult brothers.
TLDR
Two brothers with 5,10-methylene tetrahydrofolate reductase (MTHFR) deficiency are described and MTHFR deficiency should be considered in the differential diagnosis of unexplained neurologic disease in adolescents and adults. Expand
...
1
2
3
...