Methionine 3-methyl elimination

Once the azacytosine analogs are incorporated into the DNA, they are also subjed to a covalent addition of the thiol group of the DNMT and an adduct (la) similar to (I) in Figure 8.5 is formed. This addud (la) in most cases also reacts with S-adenosyl methionine (II) to a methylated addud (Ilia). But due to the absence of an a-proton the enzyme carmot be liberated by elimination and remains trapped to DNA (Figure 8.8). 

S-adenosyl-L methionine (ADO-Met) dependent DNA methyl transferase catalyzed the transfer of a methyl group from AdoMet to a specific nucleotide within the DNA helix (Cheng et al., 1993). In a concerted reaction in the enzyme active site (Fig X) with a simultaneous addition of methyl residue of AdoMet to the cytosine ring and with an elimination of the ring proton by a water molecule requires involving seven heavy nuclei (two ofCys 81, four of AdoMet and one of water. An estimation with aid of Eq. 2.44 leads to value of the reaction synchronization factor asyn 10 4, that does not rule out the concerted mechanism, if the activation energy is less than 10 kcal/mole Nevertheless, a... 

Cobalmin Deficiency. Pernicious anemia is the disease associated with vitamin Bi2 deficiency. It is usually caused by the inability to produce intrinsic factor. Indeed, many times the vitamin must be administered by injection. The blood picture, a megaloblastic anemia, is indistinguishable from that caused by folic acid deficiency. Indeed folic acid supplements can mask the blood picture. This is illustrated in Fig. 8.53. Removal of ad-enosyl cobalamin eliminates the regeneration of tetrahydrofolate during the methylation of homocysteine to methionine. Folic acid supplements provide a fresh source of tetrahydrofolate coenzymes. DNA synthesis can continue and new erythrocytes form. Excess folic acid also may compete for the available vitamin, further exacerbating vitamin deficiency. 

Methionine and Vitamin E. Combinations of methionine and vitamin E have been found to be antagonistic to selenium toxicity. In one study, selenium concentrations in the liver and kidneys of rats fed selenium-containing diets with methionine and vitamin E were less than the concentrations found in the livers and kidneys of rats fed selenium with either methionine or vitamin E alone (Levander and Morris 1970). The results are compatible with the hypothesis that methionine detoxifies selenium by forming methylated derivatives of selenium that are eliminated in the urine and in expired air (see Section 3.4.4) or that methionine and selenomethionine are in the same pool of amino acids and that by increasing the amount of methionine relative to selenomethionine, the probability of selenomethionine being randomly inserted into proteins during synthesis decreases (Stadtman 1977,1980,1983,1987, 1990). As discussed in Section 3.11, methionine administered as an antidote for acute selenium toxicity in rats was ineffective (Lombeck et al. 1987). This result supports a mechanism of action involving protein synthesis rather than a methylation mechanism hypothesis. 

A more direct y replacement of the hydroxyl of homocysteine or 0-phosphohomoserine by a sulfide ion has also been reported for both Neurospora and green plants.Methylation of homocysteine to methionine (Fig. 24-13) has been considered previously, as has the conversion of homoserine to threonine by homoserine kinase and the PLP-dependent threonine synthase (p. 746, Fig. i4-7).254-255a standard PLP-requiring P elimination converts threonine to 2-oxobutyrate, a precursor to isoleucine (Fig. 24-13). ... 

Strutural and electronic effects should play an important role in the electrocatalytic processes described above which appear to require the presence, in the thiol substrate molecule, of an activating -COOH (in cysteine) or of a derived ester group (in cysteine methyl ester[6]). In fact, not only the replacement of -SH at the cysteine molecule (e.g., by -OH or -SMe to form serine or methionine, respectively), but also the elimination of the -COOH group (to give 2-aminoethanethiol) results in complete loss of the electrocatalytic effect which, however, is maintained upon abstraction of the amino group (to form mercaptoacetic acid). Moreover, the replacement of the -COOH moiety in the mercaptoacetic acid formula, e.g,, by NH, CH, -CH SH or -OH (to give... 

Mercaptide Elimination. Kallio and Larson have described an oxidative degradation of methionine by a Pseudomonas. A pyridoxal phosphate enzyme eliminates methyl mercaptan and ammonia, leaving a-ketobutyrate. The methyl mercaptide is oxidized to dimethyl disulfide. 

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