Methylation homocysteine

N5-Methyltetrahydrofolate homocysteine methyl-transferase (= methionine synthase). This reaction is essential to restore tetrahydrofolate from N5-methyltetrahydrofolate (Fig. 2). 

In mammals and in the majority of bacteria, cobalamin regulates DNA synthesis indirectly through its effect on a step in folate metabolism, catalyzing the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate via two methyl transfer reactions. This cytoplasmic reaction is catalyzed by methionine synthase (5-methyltetrahydrofolate-homocysteine methyl-transferase), which requires methyl cobalamin (MeCbl) (253), one of the two known coenzyme forms of the complex, as its cofactor. 5 -Deoxyadenosyl cobalamin (AdoCbl) (254), the other coenzyme form of cobalamin, occurs within mitochondria. This compound is a cofactor for the enzyme methylmalonyl-CoA mutase, which is responsible for the conversion of T-methylmalonyl CoA to succinyl CoA. This reaction is involved in the metabolism of odd chain fatty acids via propionic acid, as well as amino acids isoleucine, methionine, threonine, and valine. 

Homocysteinuria (cystathionine synthase or homocysteine methyl transferase)... 

Answer A. Homocysteine, the substrate for the enzyme, accumulates increasing the risk of deep vein thrombosis and disrupting the normal crosslinking of fibrillin. Deficiency of homocysteine methyl transferase would cause homocystinuria, but would also predispose to megaloblastic anemia. 

Answer C Only methionine is degraded via the homocysteine/cystathionine pathway and would be elevated in the plasma of a cystathionine synthase-deficient patient via activation of homocysteine methyl-transferase by excess substrate. 

This cofactor is involved in the synthesis of acetic acid from C02,869 methionine from homocysteine (catalyzed by IV-methyltetrahydrofolate-homocysteine methyl transferase)870 and in the... 

S. cerevisiae converts inorganic Se to SeMet and incorporates it into the cellular protein in place of Met. The biosynthesis of SeMet proceeds via SeCys in analogy to that of Met, as was demonstrated in a study of a mutant strain of yeast requiring Met for growth due to a lack of homocysteine methyl transferase activity. When grown in Se-containing media, this strain produces SeCys, but no SeMet (Mason, 1994). While most of the SeCys is synthesized without involving Se-specific enzymes, recent studies indicate that some of the SeCys is also produced by a specific tRNA and incorporated into a 25 kDa... 

An alternative reaction for the remethylation of homocysteine to methionine can be accomplished by betaine homocysteine methyltrans-ferase, which uses betaine instead of 5-MTHF as the methyl donor. Unlike the MS reaction, which is believed to be ubiquitously present in all tissues, the betaine homocysteine methyl-transferase reaction occurs only in the liver and kidney. Betaine is not a required nutrient since the liver can synthesize betaine from choline. Betaine supplements, however, have been shown to lower plasma total homocysteine concentrations successfully in subjects with deficient homocysteine remethylation due to defects in MTHFR or MTRR and in those with deficient CBS activity. 

Although, as shown in Table 10.1, there are plausible mechanisms to suggest that homocysteine is a causative factor in cardiovascular disease, it is possible that hyperhomocysteinemia is a result of the renal damage that is an early event in cardiovascular disease, thus a proxy marker of disease rather than a causative factor (Jacobsen, 1998 hangman and Cole, 1999 Kircher and Sinzinger, 2000). in chronic renal failure, hyperhomocysteinemia is associated with cardiovascular disease, probably because of both impaired excretion of homocysteine and impaired activity of betaine homocysteine methyl-transferase elevated plasma dimethylglycine predicts plasma homocysteine (McGregor et al., 2001). 

Demyelination is because of failure of the methylation of arginine of myelin basic protein. The nervous system is especially vulnerable to depletion of S-adenosylmethionine in vitamin B12 deficiency because, unlike other tissues, it contains only methionine synthetase, which is vitamin B12-dependent and not vitamin B12-independent homocysteine methyl transferase that uses betaine as the methyl donor (Section 10.3.4 Weir and Scott, 1995). 

Methylation of homocysteine by 5-methyltetrahydrofolate-homocysteine methyl reductase depends on an adequate supply of 5-methyltetrahydrofoIate. The unmethylated folate is recycled in a cobalamin-dependent pathway, by remethylation to 5,10-methylene-tetrahydrofolate, and subsequent reduction to 5-methyltetrahydrofolate. The transferase enzyme, also named 5,10-methyltretrahydrofolate reductase catalyzes the whole cycle [3,91]. S-adenosylmethionine and 5-methyltetrahydrofolate are the most important methyl unit donors in biological system. S-adenosylmethionine is reported to regulate methylation and transsulfuration pathways in the homocysteine metabolism [3,91]. 

Homocysteine methyl transferase and glycinamide ribonucleotide (GAR) trans-formylase are examples of enzymes that require THF-coenzymes. 

Defective Activity of N -Methyltetrahydrofolate Homocysteine Methyl-Transferase and Cobalamin Activation... 

The syntheses of 5-thio-D-arabinose and -lyxose have been achieved conventionally by thiocarboxylate displacements on 5-sulphonate ester derivatives of these sugars, and their methyl glycosides were also prepared, both anomers being obtained. Methyl 5-thiopentopyran-osides (D-arabino. L-lyxo, D-ribo. and D-lyxo derivatives) have also been prepared from methyl 5-thio-3-0-tosyl-o<-D-xylopyranoside as outlined in Scheme 1. The syntheses of S-(5 -deoxy-5 -adenosyl)-(+)-2-methylhomocysteine (14.) has been achieved in two steps from (+)-2-methyl-homocysteine. Methyl 2-0-tosyl-4,6-thioanhydro-K-... 

Isomerizations, e. g. methylmalonyl-CoA to succinyl- Vitamin B,2 CoA. Also ribonucleotide triphosphate reduction, homocysteine methylation, tRNA methylation, methane production by methanogenic bacteria, etc. 

Homocysteine metabolism involves three key enzymes methionine synthase, betaine homocysteine methyl transferase (BHMT) and cystathione p-synthase. Both vitamin B12 and folate are required in the methylation of homocysteine to methionine via metheonine synthase after donation of a methyl group from SAM during the methylation process. Homocysteine is also methylated by betaine in a reaction catalysed by BHMT and does not involve vitamin B12 and folate. The other metabolic fate for homocysteine is the transsulfuration pathway which degrades homocysteine to cysteine and taurine, and is catalysed by cystathione p-synthase with vitamin Bg as coenzyme. 

Homocysteine methyl transferase, an enzyme required for the synthesis of methionine (an amino acid), also requires a THF-coenzyme. 

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