The putrescine-stimulated S-adenosyl-L-methionine decarboxylases from rat liver and yeast were strongly inhibited by Berenil and to a lesser extent by Pentamidine. Ten times greater drug concentrations were needed to achieve a similar level of inhibition of a Mg2+-stimulated bacterial enzyme. The inhibition was irreversible in that extensive dialyses or precipitation with (NH4)2SO4 did not rest...

Cantoni (1) has demonstrated that the requirement for adenosine triphosphate in the synthesis in vitro of creatine and N’methylnicotinamide from methionine and guanidoacetic acid and nicotinamide, respectively, is due to the formation of S-adenosylmethionine from methionine and ATP,’ the compound being the direct donor of its methyl group to the respective acceptors. As far as we are aware, no ...

S-Adenosylmethionine (SAM) synthase was engineered for biocatalytic production of SAM and long-chain analogues by rational re-design. Substitution of two conserved isoleucine residues extended the substrate spectrum of the enzyme to artificial S-alkylhomocysteines. The variants proved to be beneficial in preparative synthesis of SAM (and analogues) due to a much reduced product inhibition.

For the preparation of a carbocyclic nitrogen analogue of S-adenosylmethionine (carba-AdoazaMet, 4), a practical synthesis of (-)-aristeromycin (7) has been developed using variations of literature procedures. This approach called for a stereospecific synthesis of (3aR,6aR)-2,2-dimethyl-3a,6a-dihydrocyclopenta[1,3]dioxol-4-one ((4R, 5R)-4,5-O-isopropylidene-2-cyclopentenone) (8), which was achi...

The methionine adenosyltransferase is repressed in Saccharomyces cerevisiae during growth in the presence of excess methionine. The relationship of this repression to the level of intracellular S-adenosylmethionine is discussed. In conjunction with these studies, an ethionine-resistant mutant has been investigated which has a low level of methionine adenosyltransferase under all conditions test...

BACKGROUND Countries worldwide recommend women planning pregnancy to use daily 400 microg of synthetic folic acid in the periconceptional period to prevent birth defects in children. The underlying mechanisms of this preventive effect are not clear, however, epigenetic modulation of growth processes by folic acid is hypothesized. Here, we investigated whether periconceptional maternal folic aci...

Arsenic (As) and selenium (Se) are unusual metalloids as they both induce and cure cancer. They both cause carcinogenesis, pathology, cytotoxicity, and genotoxicity in humans, with reactive oxygen species playing an important role. While As induces adverse effects by decreasing DNA methylation and affecting protein 53 expression, Se induces adverse effects by modifying thioredoxin reductase. Ho...

The transmethylation of methyl-(14)C-methionine and methyl-(14)C-adenosylmethionine into the nonsaponifiable lipids of anaerobically grown yeast during adaptation to aerobic conditions was investigated. The rate and extent of methyl transfer increased with aeration time and was dependent upon the presence of a fermentable carbon source and O(2). Methionine and adenosylmethionine uptake rates in...

Previous studies (1, 2) have demonstrated that resting cell suspensions of Escherichia coli B not only incorporate 2,6diaminopurine into 5’-nucleotides but also metabolize it to 2methylamino-6-aminopurine, which is then converted to 5’phosphoribosyl-2-methylamino-6-aminopurine. For methyldiaminopurine synthesis, crude, cell-free extracts of E. coli B require methionine,l ATP, Mg++, and diaminop...

The organometallic H-cluster at the active site of [FeFe]-hydrogenases is synthesized by three accessory proteins, two of which are radical S-adenosylmethionine enzymes (HydE, HydG) and one of which is a GTPase (HydF). In this work we probed the specific role of H atom abstraction in HydG-catalyzed carbon monoxide and cyanide production from tyrosine. The isotope distributions of 5'-deoxyadenos...