SAM decarboxylase

Most pyrrolizidine alkaloids are esters of basic alcohols known as necine bases. The most frequently studied pyrrolizidine alkaloids are formed from the polyamines, putrescine and spermidine, and possess one of three common necine bases retronecine, heliotridine, and otonecine. Putrescine is utilized exclusively as a substrate in secondary metabolism, whereas spermidine is a universal cell-growth factor involved in many physiological processes in eukaryotes. Spermidine biosynthesis begins with the decarboxylation of SAM by SAM decarboxylase 165). The aminopropyl group is then transferred from decarboxylated SAM to putrescine by spermidine synthase to form spermidine (Scheme 5). Putrescine can be produced from ornithine by ODC. However, putrescine is derived from the arginine-agmatine pathway in pyrrolizidine alkaloid-producing plants due to the absence of ODC activity 166). 

All four diastereomers of the S-adenosylmethionine (SAM) analogue 84 have been separated. All showed similar Ki values towards SAM decarboxylase from E. A... 

RSV = Rous Sarcoma Virus SAH = S-adenosylhomocysteine SAM = S-adenosylmethionine SAM DC = SAM decarboxylase Ser = serine... 

There have been further reports (see Yols. 25 and 26) on the preparation of analogues of 5-adenosylmethionine (SAM) as inhibitors of SAM decarboxylase, with 64 and 65 being described. Compounds 66 (B=Thy, Gua) have been made for incorporation into oligonucleotides with a stretched phosphodicster backbone, designed to form triple helices. The 5 -phenylthio analogues of 8-aminoguanosine and formycin B have been reported as potential inhibitors of purine nucleoside phosphorylase. ... 

The elongation of polyamine is catalyzed by aminopropyl transferase in the presence of the donor of the aminopropyl group (dcSAM) described above. 5-Adenosylmethionine (SAM) decarboxylase is designated as SpeD. Most SAM... 

The enzyme SAM decarboxylase has been highly purified from E. coli, S. cerevisiae, and several mammalian tissues (see review in Tabor and Tabor, 1984). The enzymes from E. coli, yeast (Tabor and Tabor, 1984), and liver (Pegg, 1977) contain covalently bound pyruvate that is required for activity, but pyridoxal phosphate is not involved. In contrast, SAM decarboxylase from rat prostate is inhibited by isonicotinic acid hydrazide and by 4-bromo-3-hydroxy-... 

In higher plants, SAM decarboxylase activity has been detected in mung bean (Coppocctfl/., 1971), F/ncfl (Baxter and Coscia, 1973), carrot (Montague 1979), Helianthus (Bagni et al., 1983a), Phaseolus (Palavan and Galston,... 

In unpublished experiments, we have found that SAM decarboxylase activity in partially purified extracts of oat leaves is pyridoxal phosphate dependent, Mg " " independent, and is not stimulated by putrescine. 

Furthermore, SAM not only plays a pivotal role in PA and ethylene biosynthesis, but also in the formation of putrescine-derived alkaloids. Thus, SAM acts as a methyl donor in the conversion of putrescine into A-methylputresdne, an intermediate in the biosynthesis of nicotine (Mizusaki et al., 197 lb). Therefore, it would be interesting to explore the auxin-ethylene-PAs interaction on PA conjugates and putrescine-derived alkaloids metabolism in the above-mentioned tobacco callus tissue system. Indeed, it has been reported that inhibition of SAM decarboxylase by MGBG resulted in an increase of nicotine production in tobacco root cell suspension cultures (Blume, 1985). Unfortunately, nothing about PA conjugates was indicated in this report. 

Fig, 7. Pathways for the metabolism of methionine to 5 -methylthioadenosine (MTA) and recycling of MTA to methionine. Methionine can serve as a carbon source for the synthesis of polyamines and, in some tissues, ethylene. 5 -Methylthioadenosine is a product of both processes. Only the methylthio group of methionine is recycled, the C4 moiety for the resynthesis of methionine being derived from the ribosyl moiety of ATP. The enzymes involved are (1) SAM synthetase, (2) SAM decarboxylase, (3) various C3 transfer enzymes of polyamine biosynthesis, (4) MTA nucleosidase, (5) methylthioribose kinase, (6) three( ) uncharacterized enzymes, (7) aminotransferase, and (8) aminocyciopropane carboxylate synthase. 

---