5-Adenosyl-L-methionine SAM

The nonprotein amino acid, 1-aminocyclopropane-l-carboxylic acid, is an intermediate of ethylene biosynthesis in plants. This amino acid is synthesized from the L-a-amino acid methionine through the intermediate 5 -adenosyl-L-methionine (SAM) (Scheme 8). ... 

The possibility that many organic compounds could potentially be precursors of ethylene was raised, but direct evidence that in apple fruit tissue ethylene derives only from carbons of methionine was provided by Lieberman and was confirmed for other plant species. The pathway of ethylene biosynthesis has been well characterized during the last three decades. The major breakthrough came from the work of Yang and Hoffman, who established 5-adenosyl-L-methionine (SAM) as the precursor of ethylene in higher plants. The key enzyme in ethylene biosynthesis 1-aminocyclopropane-l-carboxylate synthase (S-adenosyl-L-methionine methylthioadenosine lyase, EC 4.4.1.14 ACS) catalyzes the conversion of SAM to 1-aminocyclopropane-l-carboxylic acid (ACC) and then ACC is converted to ethylene by 1-aminocyclopropane-l-carboxylate oxidase (ACO) (Scheme 1). 

The 0-methylation of TIQ 77a with 5-adenosyl-L-methionine (SAM) in the presence of mammalian catechol O-methyltransferase (COMT) gave... 

With the assumption that reticulines are also precursors in mammalian synthesis of morphine, it was challenging to investigate whether they could be produced by enzymatic reactions similar to those utilized in benzylisoquinoline-producing plants (274). This plan focused attention on reactions controlled by the enzyme catechol 0-methyltransferase (COMT), using 5-adenosyl-L-methionine (SAM) for the methylation reaction. Mammalian COMT is present in mammalian tissues, particularly the liver, and an enzyme preparation from rat liver was used for the experiments. It was found that (S)-norcoclaurine, which is the first isoquinoline produced in benzylisoquinoline-producing plants, was similarly O-methylated in vitro by SAM in the presence of COMT, and a reverse proportion of methylated products was obtained with the (/ )-enantiomer (277). Similar 0-methylation of (5)-4 -demethylreticuline (3 -hydroxy-N-methylcoclaurine), prepared by total synthesis (162), however, afforded almost exclusively (5)-orientaline, with a methoxy group at C-3 and not at C-4 as in (5)-reticuline (Fig. 37) (762). 

In E. coli, ThiH catalyzes the formation of the glycine imine 23 from tyrosine (26). ThiH is an oxygen-sensitive radical 5-adenosyl-L-methionine (SAM) enzyme. Its activity has been reconstituted and the mechanism outlined in Figure 8 has been proposed. It is unclear why E. coli adopts such a complex route to the glycine imine when oxidation of glycine using nicotinamide adenine dinucleotide (NAD) would accomplish the same transformation. 

Here we limit ourselves to an example of a 4Fe-4S center from the radical 5 -adenosyl-L-methionine (SAM) enzyme oxygen-independent coproporphyrinogen III oxidase HemN. This enzyme catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX during bacterial heme biosynthesis. The crystal structure of Escherichia coT/HemN revealed the presence of an unusually coordinated Iron-sulfur cluster and two molecules of SAM. 

Methylation is rarely of quantitative importance in the metabolization of xenobiotics. The methyl group is transferred from the nucleotide 5-adenosyl-L-methionine (SAM) by means of a methyl transferase. The functional groups include primary, secondary, and tertiary amines, pyridines, phenols, catechols, thiophenols, etc. The azahe-terocycle pyridine is metabolized to the A -methylpyridi-nium ion, which is more toxic than pyridine itself (Fig. 32.18). The binding properties of the ionized metabolite are disturbed by the loss of its hydrophobic feature, resulting from the polarity inversion. 

Plant 0-methylation reactions are common transformation in the biosynthesis of alkaloids and are most often catalyzed by 5 -adenosyl-L-methionine (SAM)-dependent methyltransferases (MTs) [62-72], Thus, norbelladine must be 4 -0-methylated to form 4 -0-methylbelladine, a central intermediate from which multiple biosynthetic pathways lead to various structural types of AAs (Figures 1-2). 

The three steps of methylation of norlaudanosoline (iii, iv, v) are catalyzed by three kinds of methyltransferases (60MT, CNMT, and 4 OMT). These enzymes need 5-adenosyl-L-methionine (SAM) as the methyl donor. The 60MT and CNMT from C. japonica have broad substrate selectivity. Therefore, 60MT can catalyze the 6-(9-methlyation of not only norcoclaurine (VI) but also norlaudanosoline (iii). Similarly, CNMT can catalyze the N-methylation of not only coclaurine (VII) but also 6-(9-methylnorlaudanosoline (iv). 

Adenosyl-L-methionine (SAM) was discovered in 1952 by Cantoni (1952), and its lUPAC name was designated as (25)-2-Amino-4-[[(25,35,4/ ,5/ )-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-methylsulfonio] butanoate. The molecular structure in Fig. 16.1 shows that SAM possesses a sulfonium ion with a high group transfer potential. Thus each of the attached carbons is activated toward nucleophilic attack. SAM is involved in three types of important biochemical reactions within living cells, including transmethylation, transsulfu-ration, and aminopropylation. 

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