Methionine formation

One form of methionine synthase common in bacteria uses lV -methyltetrahydrofolate as a methyl donor. Another form of the enzyme present in some bacteria and mammals uses A/ -methyltetrahydro-folate, but the methyl group is first transferred to cobalamin, derived from coenzyme B12, to form methylcobalamin as the methyl donor in methionine formation. This reaction and the rearrangement of L-methyl-malonyl-CoA to succinyl-CoA (see Box 17-2, Fig. la) are the only known coenzyme Bi2-dependent reactions in mammals. In cases of vitamin B12 deficiency, some symptoms can be alleviated by administering not only vitamin B12 but folate. As noted above, the methyl group of methylcobalamin is derived from W -methyltetrahy-drofolate. Because the reaction converting the methylene form to the 7V -methyl form of tetrahydrofo-... 

Most one-carbon transfers are promoted by one of three cofactors biotin, tetrahydrofolate, or S-adenosyhnethionine (Chapter 18). S-Adenosylmethionine is generally used as a methyl group donor the transfer potential of the methyl group in 7V -methyltetrahydrofolate is insufficient for most bios3Tithetic reactions. However, one example of the use of 7V -methyltetrahydrofolate in methyl group transfer is in methionine formation by the methionine synthase reaction (step of Fig. 22-15) methionine is the immediate precursor of... 

Some fungal species produce cyclopentenyl isocyanides, for example trichoviridin (166), which are known to be biosynthesised from tyrosine by cleavage of the aromatic ring. Despite much experimental study, the biosynthetic origin of the isocyanide carbon into the cyclopentenyl diene isocyanide acid (167) and related metabolites remains elusive [101-103], Notably the standard C j-tetrahydrofolate precursors such as methionine, formate, glycine or serine do not provide the source of this carbon, nor is cyanide incorporated into the isocyanide moiety [101-103], In summary, other than one terrestrial cyanophyte, the marine environment appears so far unique in accessing cyanide for isocyanide biosynthesis. 

While the studies of Dougall (1965) are suggestive, it has not yet been firmly established whether or not methionine also controls de novo synthesis of the carbon moieties of methionine. Of course such regulation of the four-carbon portion would be expected if the effect of exogenous methionine is exerted upon the cystathionine synthesis step, since it is at this step that both the sulfur and the four-carbon moieties become committed to methionine formation. 

Fig. 15 Methionine formation catalyzed by MetH (Enz signifies the MetH-apoenzyme), where the bound corrinoid shuttles between MeCbl (3), in a base-off/His-on form, and cob(I)alamin (Bi2s, 40") [125]...

The role of the S-methylmethionine-homocysteine or S-adenosylme-thionine-homocysteine methyltransferases in microorganisms or plants is far from clear. The latter activity participates in methionine formation according to Eq. (6). 

Incubations were set up as specified in Fig. 3, resulting in the consumption of more than 90 % of the substrates according to n. m. r. analysis of suitable model compounds the methionine produced was isolated by ion exchange technique and subsequently converted into its bis-trimethylsilyl (bis-TMS) derivatives upon reaction with N-(trimethylsilyl)diethylamine. Control experiments, in which the substrates, or homocysteine, were omitted from the incubations, gave no trace of methionine. A non-catalyzed methionine formation, detectable in the absence of the enzyme preparation, proceeded with a rate too low to seriously compete with the enzyme-catalyzed reaction. 

Choline, an essential nutrient for humans, is consumed in many foods. It is part of several major phospholipids (including phosphatidylcholine - also called lecithin) that are critical for normal membrane structure and function. Also, as the major precursor of betaine it is used by the kidney to maintain water balance and by the liver as a source of methyl groups for the removal of homocysteine in methionine formation. Finally, choline is used to produce the important neurotransmitter acetylcholine (catalyzed by choline acetyltransferase in cholinergic neurons and in such non-nervous tissues as the placenta). Each of these functions for choline is absolutely vital for the maintenance of normal function. 

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