High impact information on S-adenosylmethioninamine

• We conclude that urinary excretion of decarboxylated-S-adenosylmethionine represents a valid biochemical indicator of ornithine decarboxylase inhibition in humans, whereas urinary polyamines are of no value [1].
• The short-lived enzyme S-adenosylmethionine decarboxylase uses a covalently bound pyruvoyl cofactor to catalyze the formation of decarboxylated S-adenosylmethionine, which then donates an aminopropyl group for polyamine biosynthesis [2].
• In order to investigate the substrate binding sites, new sulfonium-deaminated analogs of S-adenosyl(5')-3-methylthiopropylamine have been synthesized and assayed as substrates and as inhibitors of the reaction [3].
• Hepatic decarboxylated S-adenosylmethionine content was reduced by more than 90% for at least 8 h by treatment with methylglyoxal bis(guanylhydrazone), a potent reversible inhibitor of S-adenosylmethionine decarboxylase, but had returned to control levels by 24 h [4].
• Ectopic expression of ODC-Az gene in hamster malignant oral keratinocytes led to reduce ODC activity and the subsequent demethylation of 5-methyl cytosines, presumably via the ODC/ polyamines/ decarboxylated S-adenosylmethionine (dc-AdoMet) pathways [5].

Biological context of S-adenosylmethioninamine

• Acetylation of decarboxylated S-adenosylmethionine by mammalian cells [6].
• This resumption of a normal growth rate occurred prior to the reduction in the content of cellular decarboxylated S-adenosylmethionine, suggesting that this nucleoside (which increases in concentration several hundred-fold in cells treated with 2-difluoromethylornithine) does not cause the reduction of cell growth [7].
• A modest similarity found was restricted to a relatively short peptide domain apparently involved in the binding of decarboxylated S-adenosylmethionine, the common substrate for both enzymes [8].

Associations of S-adenosylmethioninamine with other chemical compounds

• The rate of acetylation of decarboxylated S-adenosylmethionine was more than twice that of spermidine at saturating substrate concentrations, and decarboxylated S-adenosylmethionine was an active inhibitor of the acetylation of histones by nuclear extracts from rat liver [6].
• The acetylation of decarboxylated S-adenosylmethionine occurred in vivo in SV-3T3 cells exposed to the ornithine decarboxylase inhibitor 2-(difluoromethyl)ornithine [6].
• Inhibition of spermidine synthase by MEA was competitive with respect to one of the substrates putrescine, but not competitive with respect to the other substrate decarboxylated S-adenosylmethionine [9].
• In our homogeneous immunoassay, the percentage molar cross-reactivity of dcSAM with MTA-7H8 was 0.01% and the detection limit of MTA was 2.6 pmol/well [10].
• S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme of the polyamine synthetic pathway providing decarboxylated S-adenosylmethionine for the formation of spermidine and spermine, respectively [11].

Gene context of S-adenosylmethioninamine

• Inhibition of spermidine synthase by MTPA was competitive with respect to a substrate putrescine (Ki, 3.3 = 10(-7) M), but not competitive with another substrate decarboxylated S-adenosylmethionine (dec AdoMet) [12].
• Concomitantly, S-adenosylmethionine decarboxylase activity increases 7-fold and the concentration of decarboxylated S-adenosylmethionine 450-fold [13].
• Four cDNAs for spermidine synthase (SPDS), which converts the diamine putrescine to the higher polyamine spermidine using decarboxylated S-adenosylmethionine as the co-factor, were isolated from Nicotiana sylvestris, Hyoscyamus niger, and Arabidopsis thaliana [14].
• Treatment with ornithine decarboxylase inhibitors leads to a marked increase of decarboxylated S-adenosylmethionine (dc-SAM) in various tissues, accompanied by the concomitant formation of a metabolite of dc-SAM [15].
• Spermidine synthase catalyzes the transfer of the aminopropyl group from decarboxylated S-adenosylmethionine to putrescine in the biosynthesis of spermidine [16].

Analytical, diagnostic and therapeutic context of S-adenosylmethioninamine

• A highly sensitive HPLC method for the determination of decarboxylated S-adenosylmethionine (dc-SAM) by fluorometric detection was developed [17].
• Animals from each group were killed, distal colonic tissue harvested and the levels of S-adenosylmethionine, S-adenosylhomocysteine and decarboxylated S-adenosylmethionine measured by high performance liquid chromatography [18].

References