Methionine reductase

Besides thiol repair there also exists direct repair for one of the oxidation products of methionine, methionine sulfoxide. The enzyme peptide methionine sulfoxide reductase reduces the methionine sulfoxide formed in proteins due to oxidation and is therefore able to reconstitute the normal protein (Fig. 3). Besides methionine sulfoxide there exists a further oxidation product of methionine, methionine sulfone, which can not be repaired. The cycle of methionine oxidation and efficient methionine sulfoxide repair, and the early and easy oxidation of the methionine in proteins, led some authors to hypothesize that methionine acts as an intramolecular antioxidant for some proteins and so protects other amino acids from oxidation [12]. Besides the peptide methionine sulfoxide reductases, there also exists methionine reductases able to... 

Supplements of 400 Ig/d of folate begun before conception result in a significant reduction in the incidence of neural mbe defects as found in spina bifida. Elevated blood homocysteine is an associated risk factor for atherosclerosis, thrombosis, and hypertension. The condition is due to impaired abihty to form methyl-tetrahydrofolate by methylene-tetrahydrofolate reductase, causing functional folate deficiency and resulting in failure to remethylate homocysteine to methionine. People with the causative abnormal variant of methylene-tetrahydrofolate reductase do not develop hyperhomocysteinemia if they have a relatively high intake of folate, but it is not yet known whether this affects the incidence of cardiovascular disease. 

The dihydrofolate reductase enzyme (DHFR) is involved in one-carbon metabolism and is required for the survival of prokaryotic and eukaryotic cells. The enzyme catalyzes the reduction of dihydrofolate to tetrahydrofolate, which is required for the biosynthesis of serine, methionine, purines, and thymidylate. The mouse dihydrofolate reductase (mDHFR) is a small (21 kD), monomeric enzyme that is highly homologous to the E. coli enzyme (29% identify) (Pelletier et al., 1998). The three-dimensional structure of DHFR indicates that it is comprised of three structural fragments F[l], F[2] andF[3] (Gegg etal., 1997). 

Flavin Mononucleotide (FMN) Methionine synthase reductase, Chorismate synthase... 

MsrA, thioredoxin-dependent peptide methionine sulfoxide reductase... 

One form of remethylation deficit involves defective metabolism of folic acid, a key cofactor in the conversion of homocysteine to methionine. Methylenetetra-hydrofolate reductase (Fig. 40-4 reaction 11) reduces... 

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... 

MATTHEWS, R.G., SHEPPARD, C GOULDING, C., Methylenetetrahydrofolate reductase and methionine synthase biochemistry and molecular biology, Eur. J. Pediatr., 1998,157, S54-S59. 

Studies on three different iron-sulfur enzyme systems, which all require S-adenosyl methionine—lysine 2,3-aminomutase, pyruvate formate lyase and anaerobic ribonucleotide reductase—have led to the identification of SAM as a major source of free radicals in living cells. As in the dehydratases, these systems have a [4Fe-4S] centre chelated by only three cysteines with one accessible coordination site. The cluster is active only in the reduced... 

The best characterized B 12-dependent methyltransferases is methionine synthase (Figure 15.11) from E. coli, which catalyses the transfer of a methyl group from methyltetrahydrofolate to homocysteine to form methionine and tetrahydrofolate. During the catalytic cycle, B12 cycles between CH3-Co(in) and Co(I). However, from time to time, Co(I) undergoes oxidative inactivation to Co(II), which requires reductive activation. During this process, the methyl donor is S-adenosylmethionine (AdoMet) and the electron donor is flavodoxin (Fid) in E. coli, or methionine synthase reductase (MSR) in humans. Methionine synthase... 

MTHFR = methylene tetrahydrofolate reductase DHFR = dihydrofolate reductase SAM = S-adenosyl methionine... 

Boschi-Mueller S., Azza S., Sanglier-Cianferani S., Talfoumier F., Van Dorsselear A., and Barnalnt G. (2000), A sulfenic acid enzyme intermediate is involved in the catalytic mechanism of methionine sulfoxide reductase from E.coli, J. Biol. Chem. 275, 35908-35913. 

Moskovitz J., Flescher E., Berlett B.S., Azare J., Poston J.M., and Stadtman E.R. (1998), Overexpression of peptide-methionine sulfoxide reductase in Saccharomy-ces cerevisiae and human T cells provides them with high resistance to oxidative stress, Proc. Nat. Acad. Sci. U.S.A. 95, 14071-14075. 

The stem-loop structure in the noncoding 3 region of selenoprotein mRNAs has also been termed a SECTS element in mammals although it has a different overall structure. ° In silica analysis of the human genome sequence, using this consensus SECTS element along with the presence of the characteristic UGA codon within an exon, has led to the discovery of several new selenoproteins, including a selenium-dependent methionine sulfoxide reductase. It has been shown that a specific complex exists for selenoprotein synthesis that shuttles between the nucleus and the cytosol. This possibly protects the preformed complex for nonsense-mediated decay to allow for more efficient selenoprotein synthesis. The specific tRNA needed for selenocysteine... 

These three compounds exert many similar effects in nucleotide metabolism of chicks and rats [167]. They cause an increase of the liver RNA content and of the nucleotide content of the acid-soluble fraction in chicks [168], as well as an increase in rate of turnover of these polynucleotide structures [169,170]. Further experiments in chicks indicate that orotic acid, vitamin B12 and methionine exert a certain action on the activity of liver deoxyribonuclease, but have no effect on ribonuclease. Their effect is believed to be on the biosynthetic process rather than on catabolism [171]. Both orotic acid and vitamin Bu increase the levels of dihydrofolate reductase (EC 1.5.1.4), formyltetrahydrofolate synthetase and serine hydroxymethyl transferase in the chicken liver when added in diet. It is believed that orotic acid may act directly on the enzymes involved in the synthesis and interconversion of one-carbon folic acid derivatives [172]. The protein incorporation of serine, but not of leucine or methionine, is increased in the presence of either orotic acid or vitamin B12 [173]. In addition, these two compounds also exert a similar effect on the increased formate incorporation into the RNA of liver cell fractions in chicks [174—176]. It is therefore postulated that there may be a common role of orotic acid and vitamin Bj2 at the level of the transcription process in m-RNA biosynthesis [174—176]. 

This enzyme [EC 1.8.4.5], also known as methionine S-oxide reductase, catalyzes the reaction of L-methionine with oxidized thioredoxin to produce L-methionine S-oxide and reduced thioredoxin. Dithiothreitol can substitute for reduced thioredoxin in the reverse reaction. In addition, other methyl sulfoxides can replace methionine sulfoxide in the reverse reaction. 

METHIONINE ADENOSYLTRANSFERASE METHIONINE y-LYASE METHIONINE SULFOXIDE REDUCTASE Methionine synthase,... 

PEPTIDOMIMETIC COMPOUND PEPTIDE METHIONINE SULFOXIDE REDUCTASE... 

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