N5-methyl

Hill et al. (141) hrst observed that light-stable yellow alkylcorrinoids could be synthesized. When methylcobalamin was treated with picrate, a yellow corrinoid was isolated which was shown to be stable to light, but unstable to cyanide. Similarly, Taylor and Weissbach (67) demonstrated that the methylcorrinoid-enzyme complex of N5-methyl-tetrahydro-folate-homocysteine transmethylase was stable to light, but isolation of... 

The effects of cobalamin deficiency are most pronounced in rapidy dividing cells, such as the erythropoietic tissue of bone marrow and the mucosal cells of the intestine. Such tissues need both Die N5-N10-methylene and N10-formyl forms of tetrahydrofolate for Ihe synthesis of nucleotides required for DNA replication (see pp. 291, 301). However, in vitamin B12 deficiency, the N5-methyl form of tetrahydrofolate is not efficiently used. Because the methylated fonn cannot be converted directly to other forms of tetrahydrofolate, tie Ns-methyl form accumulates, whereas the levels of the other forms decrease. Thus, cobalamin deficiency is hypothesized to lead to a deficiency of the tetrahydrofolate forms needed in purine and thymine synthesis, resulting in the symptoms of megaloblastic anemia. 

Glycine, sarcosine, dimethyl-glycine, serine, formaldehyde, N5-methyl-FH4,... 

The most widely used methyl donor for enzymatic methyl transfer is the cofactor S-adenosyl-L-methionine (SAM). The methyl moiety on the L-methionine is supplied by another known methyl donor, N5-methyl tetrahydrofolate.30 To date, numerous enzymes that perform SAM- dependent methylation reactions have been described in plants, and several reports attempting to sort out their evolutionary relationships have been published.31- 3... 

These Cj groups may be attached to N atoms in positions 5 or 10 (Fig. 15-19) or may form a bridge between the two. N5-methyl-THF is formed in mammals by a virtually irreversible reaction... 

With the exception of N5-methyl-THF, the THF derivatives are directly synthesized from a C unit in the appropriate oxidation state, and THF. The major anaplerotic reaction is that catalyzed by serine hydroxymethyltransferase (Sec. 15.1). 

One aspect of vitamin B12 deficiency is that it results in the accumulation of W5-methyl-THF. N5-Methyl-THF is synthesized in mammals by an irreversible reaction (as shown above) if it cannot be utilized because of a deficiency of vitamin B12, then it accumulates. This causes a depletion of the other forms of THF, resulting in a deficiency of THF. Megaloblastic anemia (pernicious anemia) is associated with a deficiency of cobalamin... 

The methylene derivative may be reduced to N5-methyl-FH4, which is not reoxidized under physiological conditions. 

In Figure 14.14, vitamin B12 is required for the N5-methyl THF-dependent -=j= conversion of homocysteine to methionine. Vitamin B12 (cobalamin) is a com-plex, cobalt-containing molecule synthesized only by microorganisms (Figure... 

The importance of SAM in metabolism is reflected in the several mechanisms that provide for the synthesis of sufficient amounts of its precursor, methionine, when the latter molecule is temporarily absent from the diet. For example, choline is used as source of methyl groups to convert homocysteine into methionine. Homocysteine can also be methylated in a reaction utilizing N5-methyl THF. This latter reaction is a bridge between the THF and SAM pathways (Figure 14.17). 

Earley LF, Minko IG, Christov PP, Rizzo CJ, Lloyd RS. Mutagenic spectra arising from replication bypass of the 2,6-diamino-4-hydroxy-N5-methyl formamidopyrimi-dine adduct in primate cells. Chem Res Toxicol. 2013 26 1108—1114. 

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