Transfer of the methyl group from <i>N</i>5-methyltetrahydrofolates to homocysteine in <i>Escherichia coli</i>

Guest, J. R.; Friedman, Steven G.; Foster, M. A.; Tejerina, G.; Woods, D. D.

doi:10.1042/bj0920497

Cited by 55 publications

(31 citation statements)

References 12 publications

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“…The functions of these cofactors have been investigated and are described and discussed by Guest et al (1964a) and Guest, Friedman, Foster, Tejerina & Woods (1964b).…”

Section: Discussionmentioning

confidence: 99%

Two enzymic mechanisms for the methylation of homocysteine by extracts of Escherichia coli

Foster¹,

Tejerina²,

Guest³

et al. 1964

Biochemical Journal

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“…The functions of these cofactors have been investigated and are described and discussed by Guest et al (1964a) and Guest, Friedman, Foster, Tejerina & Woods (1964b).…”

Section: Discussionmentioning

confidence: 99%

Two enzymic mechanisms for the methylation of homocysteine by extracts of Escherichia coli

Foster¹,

Tejerina²,

Guest³

et al. 1964

Biochemical Journal

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“…2.1.1.13)] using methyl group from 5-methyltetrahydrofolate and the coenzyme methylcobalamin (vitamin B12) [17]. Methionine synthase is the only enzyme that uses both vitamin B9 (in the form of methyl-tetrahydrofolate) and vitamin B12 (in the form of methylcobalamin) [18]. The other only enzyme that uses vitamin B12 in the form of adenosylcobalamin is methylmalonyl CoA mutase.…”

Section: Perspectivesmentioning

confidence: 99%

Methionine Metabolism in Humans: New Perspectives on Epigenetic Inheritance

Venkatachalam

2014

J Mol Genet Med

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Epigenetic control by methylation is directly dependent on SAM/methionine. Free methionine aside from being used for protein synthesis is activated to universal methyl group donor SAM and the methyl group from it can be transferred mainly onto DNA, histones, mRNA and noncoding (Nc) RNA, in the nucleus and onto various cytosolic recipients by specific methyltransferases. The product S-adenosylhomocysteine (SAH) from methyltransferase reaction is cleaved into free homocysteine and adenosine. Homocysteine has two fates, one to enter methionine resynthesis which requires methionine synthase (MetS), the coenzymes N5-methyltetrahydrofolate (vitamin B9) and methylcobalamin (vitamin B12). The second option of homocysteine is to enter cysteine synthesis pathway which requires cystathionine -synthase (CBS), serine, vitamin B6 (pyridoxal phosphate) and cystathionine γ-lyase (CGL). I predict serine and vitamin B6 are the critical diverting factors in a fully developed organism where the methylation is minimal and all other factors such as MetS, B9, B12, ATP, Methionine adenosyltransferase (MAT), are more relevant during normal development or in abnormal deregulated cancer cell metabolism. In a developed organism the demethylation pathway would play a critical role during tissue regeneration and must involve hydroxylation (CH2OH), oxidation (CHO) and decarboxylation (COOH) and the corresponding hydroxylase, oxidase and decarboxylase. The hydroxylation is predicted to involve vitamin C (ascorbate) and decarboxylation would involve (vitamin B6). The control of methylation and equally the demethylation is extremely crucial for epigenetic control mechanisms (gene suppression/expression) and any dysregulation would cause abnormal tissues/cancer.

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“…The formed 5-methyltetrahydrofolate is subsequently used as a single carbon donor for methylation of L-homocysteine, resulting in the formation of L-methionine, catalyzed by methionine synthase (EC 2.1.1.13) (14). In addition to the synthesis of L-methionine, this pathway also provides the basic building block for de novo synthesis of nucleotides (adenine, guanine, and thymidine), generates single-carbon donor units in the form of SAM, and is a central part of sulfur metabolism.…”

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confidence: 99%

Methylenetetrahydrofolate Reductase Activity Is Involved in the Plasma Membrane Redox System Required for Pigment Biosynthesis in Filamentous Fungi

et al. 2010

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Methylenetetrahydrofolate reductases (MTHFRs) play a key role in biosynthesis of methionine and Sadenosyl-L-methionine (SAM) via the recharging methionine biosynthetic pathway. Analysis of 32 complete fungal genomes showed that fungi were unique among eukaryotes by having two MTHFRs, MET12 and MET13. The MET12 type contained an additional conserved sequence motif compared to the sequences of MET13 and MTHFRs from other eukaryotes and bacteria. Targeted gene replacement of either of the two MTHFR encoding genes in Fusarium graminearum showed that they were essential for survival but could be rescued by exogenous methionine. The F. graminearum strain with a mutation of MET12 (Fg⌬MET12) displayed a delay in the production of the mycelium pigment aurofusarin and instead accumulated norrubrofusarin and rubrofusarin. High methionine concentrations or prolonged incubation eventually led to production of aurofusarin in the MET12 mutant. This suggested that the chemotype was caused by a lack of SAM units for the methylation of nor-rubrofusarin to yield rubrofusarin, thereby imposing a rate-limiting step in aurofusarin biosynthesis. The Fg⌬MET13 mutant, however, remained aurofusarin deficient at all tested methionine concentrations and instead accumulated nor-rubrofusarin and rubrofusarin. Analysis of MET13 mutants in F. graminearum and Aspergillus nidulans showed that both lacked extracellular reduction potential and were unable to complete mycelium pigment biosynthesis. These results are the first to show that MET13, in addition to its function in methionine biosynthesis, is required for the generation of the extracellular reduction potential necessary for pigment production in filamentous fungi.

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Transfer of the methyl group from N5-methyltetrahydrofolates to homocysteine in Escherichia coli

Abstract: * Abbreviations for members ofthe folic acidgroup, based on PtG for pteroylglutamate: H4PtG, tetrahydropteroylmonoglutamate; H4PtG3, tetrahydropteroyltriglutamate; derivatives of these compounds are indicated as, e.g., N5-methyl-H4PtG.

Cited by 55 publications

References 12 publications

Two enzymic mechanisms for the methylation of homocysteine by extracts of Escherichia coli

Two enzymic mechanisms for the methylation of homocysteine by extracts of Escherichia coli

Methionine Metabolism in Humans: New Perspectives on Epigenetic Inheritance

Methylenetetrahydrofolate Reductase Activity Is Involved in the Plasma Membrane Redox System Required for Pigment Biosynthesis in Filamentous Fungi

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