S-Adenosylmethionine AdoMet

Takusagawa F, Fujioka M, Spies A, Schowen RL (1998) S-adenosylmethionine (adomet)-dependent methyltransferases. In Sinnott M., (ed), Comprehensive biological catalysis a mechanistic reference. Academic Press, San Diego, pp 1-30... 

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... 

Fig. 2.2.6 Mechanism of the derivatisation of S-adenosylmethionine (AdoMet), S-adenosylho-mocysteine (AdoHcy) and chloroacetaldehyde...

Fig. 12-2 S-Adenosylmethionine (AdoMet, solid bonds) bound in the active site of glycine N-methyl-transferase together with an acetate ion bound in the glycine site. Glycine was built by attaching an amino group (open bond) to the acetate (solid bonds). Possible polar interactions (0-0 and O-N < 0.31 nm and O-S < 0.4 nm) are indicated by dotted lines. Tyrosine residues located at the inner surface of the active site are also shown. From Fu et al.21...

S-Adenosylhomocysteine 592s, 778s S-Adenosylhomocysteine hydrolase 778 S-Adenosylmethionine (AdoMet,... 

Fatty acids containing one or more cyclopropane rings are present in many bacteria (p. 381).124 125 The extra carbon of the cyclopropane ring is added from S-adenosylmethionine (AdoMet) at the site of a cis double bond in a fatty acyl group of a phosphatidyle-thanolamine molecule in a membrane (Eq. 21-4).126/1263 The same type of intermediate carbocation can yield either a cyclopropane fatty acid (Eq. 21-4, step a) or a methenyl fatty acid (Eq. 21-4, step b). The latter can be reduced to a branched fatty acid. This is an alternative way of introducing methyl branches that is used by some bacteria.127... 

As part of a theoretical examination of the factors controlling the catalytic efficiency of a transmethylation enzyme (catechol O-mcthyltransfcrasc), the reaction mechanism of the non-enzymic transmethylation of catechol by S-adenosylmethionine (AdoMet, as modelled by sulfonium ion) has been elucidated by using ab initio and semiempirical quantum mechanical methods.97 The gas-phase reaction between catecholate and sulfonium is extremely fast, involving no overall barrier, and the reaction profile to some extent resembles that of a typical gas-phase 6W2 reaction. However, in aqueous solution, this reaction is very slow, with a predicted barrier of 37.3 kcal mol. Good agreement between calculated KIEs for the model reaction and measured KIEs for the enzymic reaction suggests that the transition states are similar. 

Fig. 4. Polyketide biosynthesis by gene products of the act PKS cluster. Presence of the KS/AT, CLF, and ACP is sufficient for the production of two 16-carbon polyketides, SEK4 and SEK4b both in vivo [ 103] and in vitro [107]. In the presence of the act ketoreductase (KR), aromatase (ARO) and cyclase (CYC), the octaketide intermediate is converted into DMAC. DMAC can be converted into 8-methoxy DMAC both in vivo and in vitro through the S-adenosylmethionine (Adomet)-dependent action of the tcmO methyltransferase [207]...

Once inside the cell, folates participate in a number of interconnected metabolic pathways involving (1) thymidine and purine biosynthesis necessary for DNA synthesis, (2) methionine synthesis via homocysteine remethylation, (3) methylation reactions involving S-adenosylmethionine (AdoMet), (4) serine and glycine interconversion, and (5) metabolism of histidine and formate (see Figure 8). Via these pathways. 

S-adenosylmethionine. (adoMet SAM). An enzymatic cofactor involved in methyl group transfers. 

S-methylmethionine-homocysteine methyltransferase, functions along with Sam4p in the conversion of S-adenosylmethionine (AdoMet) to methionine to control the methionine/AdoMet ratio Carbonic anhydrase poorly transcribed under aerobic conditions and at an undetectable level under anaerobic conditions involved in non-classical protein export pathway... 

The early steps in the ergot alkaloid biosynthetic pathway are outlined in Fig. 1. The first determinant and rate-limiting step is the prenylation of tryptophan to 4-(y,y-dimethylallyl)tryptophan (DMAT), catalyzed by dimethy-lallyl-diphosphate L-tryptophan dimethylallyltransferase (DMAT synthase EC 2.5.1.34) (Heinstein et al., 1971 Gebler and Poulter, 1992). The prenyl group for the DMAT synthase reaction is provided in the form of dimethylallyl diphosphate (DMAPP), which is derived from mevalonic acid. After the formation of DMAT, the free amino group of this intermediate is N-methylated with a methyl group donated by S-adenosylmethionine (AdoMet). The N-methylated DMAT is then converted into chanoclavine I by closure of the... 

The mode of formation of a methyl group seen in thymidylate is exceptional most methyl groups in biological molecules arise from the S-methyl group of methionine. Our next goal was to determine the steric course of the transfer of a methyl group from methionine or S -adenosylmethionine (AdoMet) to various C-, N-, or... 

Figure 30 The creatine (42) biosynthesis pathway consists of two enzymes L-arginine glycine amidinotransferase (AGAT) and guanidinoacetate A/-methyltransferase (GAMT). Atoms derived from glycine are shown in green, arginine in blue, and S-adenosylmethionine (AdoMet) in black.

S-adenosylmethionine (AdoMet) is a metabolically activated form of methionine involved in donating methyl groups. Transfer of a methyl group from AdoMet to a target molecule converts AdoMet to S-Adenosylhomocysteine (AdoHcy) (see here). 

S-Adenosylmethionine (AdoMet) is a metabolically activated form of methionine capable of donating a methyl group. AdoMet is formed in the reaction shown here. Transfer of a methyl group from AdoMet to a target molecule converts AdoMet to S-Adenosylhomocysteine (AdoHcy) (see here). Table 21.1 lists some important AdoMet-dependent transmethylations. Substrates range from small metabolites, such as norepinephrine, to polymers, such as DNA (see here), RNA, or proteins. 

Methylation underlies several important biological processes, including restriction and modification, mismatch error correction (a DNA repair process), and the control of eukaryotic gene expression. S-Adenosylmethionine (AdoMet) is the substrate for methylation of both RNA and DNA. Methylation occurs at the polynucleotide level, with transfer of a methyl group from AdoMet to a nucleotide residue. 

For human beings methionine is nutritionally essential and comes entirely from the diet. ITowever, the oxoacid analog of methionine can be used as a nutritional supplement. Dietary homocysteine can also be converted into methionine to a limited extent. Methionine is incorporated into proteins as such and as N-formylmethionine at the N-terminal ends of bacferial profeins (steps a and b, Fig. 24-16). In addition to its function in proteins methionine plays a major role in biological methylation reactions in all organisms. It is converted into S-adenosylmethionine (AdoMet or SAM Fig. 24-16, step e see also Eq. 17-37), ° ° which is the most widely used methyl group donor for numerous biological methylation reactions (Eq. 12-3). S-Adenosylmethionine is also the precursor of the special "wobble base" queuine (Fig. 5-33). The product of transmethylation, S-adenosylhomocysteine, is converted (step... 

The major biosynthetic pathway of ethylene in higher plants includes L-methionine, S-adenosylmethionine (AdoMet) and 1-anunocyclopropane-l-carboxylic acid (ACC) as the intermediates, and this pathway is commonly called the ACC pathway. It took a decade of extensive studies since methionine was confirmed as the precursor of ethylene in high plant tissues [24,25]. Before ACC was recognised as a direct precursor of ethylene [26,27]. However, some lower plants such as the semiaquatic fern Regnellidium diphyllum and the liverwort Riella helicophylla do not use ACC as a precursor, and there is convincing evidence for the presence of a non-ACC pathway [5]. However, the biochemical characterisation of this non-ACC pathway is yet to be performed. 

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