5 -Methylthioadenosine reactions

ACC 71 synthase, i. e. (S)-adenosylmethionine methylthioadenosine lyase (EC 4.4.1.14), has been purified from several plant tissues [116]. Recently, ACC synthase cDNA clones have been isolated and sequenced from wounded fruit tissues of tomato, winter squash, zucchini, ripening apple and tomato fruit. Using the polymerase chain reaction (PCR), four different ACC synthase gene fragments were obtained by amplification of cDNA derived from mRNA of tomato... 

Cyclization. A second kind of reaction is represented by the conversion of S-adenosylmethionine to aminocyclopropanecarboxylic acid, a precursor to the plant hormone ethylene (see Chapter 24).159 The quinonoid intermediate cyclizes with elimination of methylthioadenosine to give a Schiff base of the product (Eq. 14-27).160-161a The cyclization step appears to be a simple SN2-like reaction.162... 

Adenine phosphoribosyltransferase catalyzes the conversion of adenine to AMP in many tissues, by a reaction similar to that of hypoxanthine-guanine phosphoribosyltransferase, but is quite distinct from the latter. It plays a minor role in purine salvage since adenine is not a significant product of purine nucleotide catabolism (see below). The function of this enzyme seems to be to scavenge small amounts of adenine that are produced during intestinal digestion of nucleic acids or in the metabolism of 5 -deoxy-5 -methylthioadenosine, a product of polyamine synthesis. 

Adams and Yang (10) have suggested that the S atom of methionine is recycled in the ethylene reaction pathway, as shown in Fig. 2. In this scheme, 5 -methylthioadenosine, the residual molecule which derives from the reaction converting SAM to ACC, is further metabolized to 5 -methylthioribose, which then transfers the S-methyl group to homoserine to form methionine. This scheme is hypothetical, and the enzymes necessary for all these reactions have not as yet been demonstrated. 

The purine requirement for this enzyme is unknown and it is likely that an AdoMet analog based on purine or methionine could affect both polyamine and methylation reactions. In trypanosomatids, the salvage enzyme methylthioadenosine (MTA) phosphorylase has been found to have a broad substrate requirement (Fig. 7.1)... 

AdoMet is an important metabolic intermediate in all organisms, from bacteria to higher animals and plants. It supplies the methyl group to nucleic acids, phenolic substances and alkaloids, or the propylamine moiety to polyamines after decarboxylation. The methionine cycle operates in animals and microorganisms in relation to polyamine synthesis. Thus, enzymes which catalyse all of these reactions are present in all organsims. However, two enzymes in the ACC pathway, ACC synthase (AdoMet methylthioadenosine-lyase) and ACC oxidase, are unique to higher plants. ACC is also malonylated to form N-malonyl ACC, which does not serve as a precursor of ethylene [48,49]. 

The reaction -will begin with the formation of a Schiff base between pyridoxal-5 -phos-phate and the amino group of 5-adenosylmethionine (external aldimine, as opposed to the internal aldimine in which PLP is connected to a lysine on the enzyme). In usual fashion for PLP enzymes, the a-hydrogen -will be extracted from S-adenosylmethionine (step 2, below). Then the next series of 7i-electron transfers (step 3) will eliminate S-methylthioadenosine and form the three-membered ring. Finally, f-aminocyclopropane-1-carboxylate (ACC) will be released, and the original internal aldimine between PLP and lysine veill be restored, so that the enzyme and cofactor are ready for another round of synthesis. The second product is S-methylthioadenosine. 

The mechanism of the proposed transfer of the methylthio moiety of S -methylthioadenosine has not been studied, but on theoretical grounds the reaction would be expected to proceed through methylmercaptan either in free or enzyme-bound form. Results of isotope feeding experiments (Baur and Yang, 1972b Adams and Yang, 1977) are not inconsistent with this... 

The complex reactions of a second recycling pathway lead to the synthesis of Met 8 from methylthioadenosine (MTA 9). The methylthio group of Met derives from MTA and is not built upon methylation of homocysteine 8. This pathway is not known in mammals [32],... 

Adenosine triphosphate is the specific nucleotide of this reaction. Active methionine is the methyl donor to various acceptors, e.g., nicotinamide, glycocyamine, adrenaline. Transmethylations are catalyzed by specific methylpherases The product of transmethylation is usually the iV-methyl derivative of the acceptor while active methionine is converted to (S-adenosylhomocysteine. Active methionine may undergo hydrolytic cleavage in yeast to yield 5 -methylthioadenosine and homoserine 96). The reaction may not be enzymic. This adenosine derivative had been isolated long before active methionine was known 96). Betaine and certain sul-fonium compounds structurally related to active methionine, e.g., dimethyl-/8-propiothetin [(CHs)2= S—CH —CHj—COOH] 97), can also act as methyl donors for homocysteine in liver suspensions 98). 

---