Methylenetetrahydrofolate reductase MTHFR enzyme

Methylenetetrahydrofolate reductase (MTHFR) catalyzes the NAD(P)H-dependent reduction of 5,10-methylenetetrahydrofolate (CH2-THF) to 5-methyltetrahydrofolate (CH3-THF). CH3-THF then serves as a methyl donor for the synthesis of methionine. The MTHFR proteins and genes from mammalian liver and E. coli have been characterized,12"15 and MTHFR genes have been identified in S. cerevisiae16 and other organisms. The MTHFR of E. coli (MetF) is a homotetramer of 33-kDa subunits that prefers NADH as reductant,12 whereas mammalian MTHFRs are homodimers of 77-kDa subunits that prefer NADPH and are allosterically inhibited by AdoMet.13,14 Mammalian MTHFRs have a two-domain structure the amino-terminal domain shows 30% sequence identity to E. coli MetF, and is catalytic the carboxyterminal domain has been implicated in AdoMet-mediated inhibition of enzyme activity.13,14... 

Methylenetetrahydrofolate is then reduced to CH3-THF by the vitamin B2 (riboflavin)-dependent enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), using NADPH as cosubstrate. MTHFR is the key enzyme for diverting 5,10-methylentetrahydrofolate to methylation of homocysteine or to DNA synthesis though the conversion of uracil to thymidine. 

Weisberg I, et al, A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 1998 64(3) 169-172. 

Methylenetetrahydrofolate reductase (MTHFR) is encoded by the MTHFR gene located on chromosome lp36.22. It is the rate-limiting enzyme in the folic acid metabolic cycle that is critical for the... 

The deficiencies of cystathionine )5-synthase (CBS), sulfite oxidase, and methylenetetrahydrofolate reductase (MTHFR) may all result in central nervous system dysfunction, in particular mental retardation [1-3]. Defects of CBS and sulfite oxidase both cause dislocated lenses of the eyes, but the phenotypes are different otherwise. The manifestations of CBS deficiency, the most common of these disorders, and MTHFR deficiency range from severely affected to asymptomatic patients both may cause vascular occlusion. Deficiency of sulfite oxidase is clinically uniform, but genetically heterogeneous, and functional deficiency of the enzyme can result from several inherited defects of molybdenum cofactor biosynthesis [2, 4]. Hereditary folate malabsorption and defects of cobalamin transport (transcobala-min II deficiency) or cobalamin cofactor biosynthesis (cblC-G diseases) may cause megaloblastic anemia, in addition to CNS dysfunction [3, 5, 6]. 

Methylentetrahydrofolate reductase (MTHFR) is another key enzyme of 5-FU metabolism, alternating 5-FU sensitivity indirectly by folate pool variations. MTHFR plays an important role in the action of 5-FU, an inhibitor of TS, by converting 5,10-methylenetetrahydrofolate, a substrate of TS, to 5-methyltetrahydrofolate (19). 

MSCB (master seed cell bank) 746 MTHFR, see methylenetetrahydrofolate reductase MTT (3,4,5-dmethylthiazol-2yl-2,5-diphenyl tetrazolium bromide) 640 Mucolytic enzymes 1376 Mucopolysaccharidosis 24, 862 Multiangle light scattering (MALS) 162 Multilamellae vesicles 1370 Multifunctional-type nanodevice (MEND) 1522... 

Methyltetrahydrofolate (5-MTHF). The circulating form of folic acid in humans. 5-MTHF is produced by 5,10-methylenetetrahydrofolate via the action of MTFH reductase (MTHFR). 5-MTHF scavenges peroxynitrites, the main BH4 oxidant, and helps to BH4 regeneration inside the human vascular wall. It is considered the key mediator of folic acid s vascular effects (as in the presence of the C677T mutation in MTHFR gene that reduces enzyme s activity almost by half). 

MTHFR Methylenetetrahydrofolate reductase MS Methionine synthase THF Tetrahydrofoiate A an enzyme... 

Figure 44.1 Folate-mediated one carbon metabolism network. Enzymes and transport proteins are enclosed in rectangular boxes. AHCY S-adenosyDiomocys-teine hydrolase AICART 5-aminoimidazole carboxamide ribonucleotide transferase BHMT betaine homocysteine methyltransferase CBS cystathionine beta-synthase DHFR dihydrofolate reductase FR folate receptor FTCD formimidoyltransferase cyclodeaminase GART glycinamide ribonucleotide transformylase MATs (MATI/MATIII) adenosylmethionine transferase enzyme I/III MS methionine synthase MSR methionine synthase reductase MT methyltransferase MTHFD methylenetetrahydrofolate dehydrogenase MTHFR 5,10-methylenete-trahydrofolate reductase MTHFS 5,10-methylenetetrahydrofolate synthase. RFC reduced folate AdoMet 5-adenosylmethionine AdoHcy S-adenosylhomocysteine Hey homocysteine SHMT serine hydroxymethyltransferase TS thymidylate synthase.

---