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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Saccharomyces cerevisiae strain 83384-B3 carries the sai-1 mutation which confers sensitivity to S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). It was shown that the mutant is impermeable to precursors of ribonucleic acid (RNA) and protein during inhibition by SAM (0.2 mM). Inhibition of uptake of adenine and uracil was nearly complete 3 h after growth in the presence of SAM and the uptake of leucine was at least 10-fold lower. The incorporation of 3H-adenine into ribosomal RNA, transfer RNA and heterodisperse RNA, believed to be messenger, was reduced 10-fold when measured after 1 h inhibition. The inhibition of growth was completely reversed by methionine (2.0 mM) in cells previously exposed to SAM for 90 min. The polysome content in cells inhibited by SAM was 25% less than the control after 4 h inhibition. Ribosome synthesis increased only about 40% in the presence of SAM and about 5-fold in the control over an 8 h period. All classes of RNA were synthesized during inhibition.
Mol Gen Genet 1976 Mar 30
PMID:Macromolecule synthesis in a mutant of Saccharomyces cerevisiae inhibited by S-adenosyimethionine. 77 1

The action of S-adenosyl-l-homocysteine (S-Ado-Hcy), its four structural analogues S-Ino-Hcy, S-Guo-Hcy, S-Urd-Hcy, S-Cyd-Hcy and the five corresponding sulfoxides on tRNA methylases has been investigated. The data obtained in the study of overall incorporation of 14CH3-groups into an unfractioned tRNA preparation suggested that both the affinity of the inhibitors tested for various methylases and the type of inhibition were different. The experiments performed with unfractioned tRNA preparation permit to get an idea of the average inhibitory potency of each of the compounds. The study of their action on individual tRNA methylases by means of fractionation of minor components produced demonstrated that the affinity of the inhibitors tested for various methylases was really different. Thus, S-Ado-Hcy, S-Ino-Hcy and S-Urd-Hcy practically do not inhibit m1A methylase but have the highest affinity for m5C methylase. In an experiment with tRNAPhe which is a substrate for a single, namely m5C methylase, the type of inhibition of this methylase by S-Cyd-Hcy was revealed; it was found to be non-competitive with respect to S-Ado-Met, and the S-Cyd-Hcy concentration reducing the methylation by 50 percent was 1.2-10(-4) M.
Mol Biol (Mosk)
PMID:[Inhibiting effect of S-adenosyl-L-homocysteine and its structural analogs on the process of enzymatic methylation of tRNA]. 78 40

GpppG was modified to m7 GpppGm by a cytoplasmic extract, prepared from embryonic lens cells, in a reaction mixture which contained S-adenosyl-methionine as methyl group donor. The appearance of m7 GpppGm was a function of time and lens extract concentration. S-adenosyl-homocysteine inhibited both the m7G and Gm modification reactions. Analogues of GpppG, pG, ppG and pppG were relatively ineffective as substrates.
Mol Biol Rep 1977 Jun
PMID:Detection of methyltransferase activities which modify Gppp G to m7GpppGm in embryonic chick lens. 88 98

Experiments were performed on isolated perfused guinea-pig hearts (n = 45) to further evaluate the stimulus that triggers cardiac adenosine production. Stimulation of hearts with isoproterenol (4 nM, 20 min) enhanced left ventricular dP/dtmax, heart rate and myocardial oxygen consumption within 1 min to new steady state values, whereas coronary venous adenosine concentration only transiently increased reaching its maximum between 1 and 3 min of stimulation. Rate of accumulation of S-adenosylhomocysteine (SAH), a measure of the free cytosolic adenosine concentration, was steepest immediately following onset of stimulation and then progressively declined. Similar to adenosine, changes in coronary venous pO2 were phasic and adenosine release and pO2 closely correlated. Norepinephrine (20 nM) which increased myocardial oxygen consumption to a comparable extent as isoproterenol (4 nM) further decreased coronary venous pO2 and increased coronary venous adenosine. When myocardial oxygen supply was systematically varied by changing coronary perfusion pressure from 60 to 90 and 35 cmH2O, respectively, the adenosine release during isoproterenol (2 nM) was markedly enhanced at 35 cmH2O but blunted at 90 cmH2O. Similarly SAH accumulation was greatest at 35 cmH2O and smallest at 90 cmH2O. It is concluded that changing myocardial oxygen consumption is not a sufficient cause to enhance adenosine formation. Myocardial oxygenation as reflected by changes in coronary venous pO2 closely correlates with changes in free cardiac adenosine as evidenced by two independent indices: tissues SAH and coronary venous adenosine concentration. The stimulus triggering cardiac adenosine formation is most likely the imbalance of oxygen supply and oxygen demand.
J Mol Cell Cardiol 1991 Apr
PMID:Cardiac adenosine production is linked to myocardial pO2. 194 83

(+/-)-6' beta-Fluoroaristeromycin (F-C-Ado) is a potent and competitive inhibitor of purified S-adenosylhomocysteine (AdoHcy) hydrolase isolated from murine L929 cells (Ki = 3.1 nM). It also inhibits vaccinia virus and vesicular stomatitis virus replication in L929 cells, at a 90% inhibitory dose (ID90) of 3.5 and 13 microM, respectively. Considering the close correlation that has been found between Ki and ID90 for other AdoHcy hydrolase inhibitors [Biochem. Pharmacol. 38:1061-1067 (1989)], F-C-Ado is a weaker antiviral agent than expected from its Ki value. Nevertheless, the antiviral action of F-C-Ado appears to be targeted at AdoHcy hydrolase. The fact that F-C-Ado is less antivirally active than expected may be due to its further metabolism to its ATP and GTP derivatives. The cytotoxicity of F-C-Ado may be attributed to both its inhibitory effect on AdoHcy hydrolase and the inhibitory effect of its phosphorylated products on host cell RNA synthesis.
Mol Pharmacol 1991 Jun
PMID:Mechanism of antiviral and cytotoxic action of (+/-)-6' beta-fluoroaristeromycin, a potent inhibitor of S-adenosylhomocysteine hydrolase. 205 90

Several thiols, including homocysteine and cysteamine, have been shown to increase glutathione levels in C3H/10T1/2 Cl 8 cells [Biochem. Pharmacol. 39:421-429 (1990)]. The present paper shows that cysteamine also increases homocysteine export from these cells. Cellular glutathione content and export of glutathione and homocysteine increased with increasing doses of cysteamine. Twenty-four hours after addition, 300 microM cysteamine increased both glutathione content and homocysteine export 3-4-fold. No change in the ratio between reduced and oxidized glutathione could be detected, suggesting that the cysteamine effect was not due to reduction of pools of oxidized glutathione. The elevation of glutathione occurred rapidly but declined between 24 and 48 hr after addition of cysteamine, whereas the homocysteine export increased momentarily after cysteamine exposure and then proceeded at a rate similar to that from untreated control cells. The cysteamine-induced increase in glutathione was completely prevented by the gamma-glutamylcysteine synthetase inhibitor buthionine sulfoximine but was not affected by inhibition of homocysteine formation by 3-deazaaristeromycin. Buthionine sulfoximine did not prevent the increase in homocysteine export by cysteamine, and only a small increase in homocysteine export was observed when the cells were exposed to 3-deazaaristeromycin before treatment with cysteamine. Two major conclusions were drawn. 1) Increase of glutathione content and homocysteine export by cysteamine were independent events, indicating that glutathione status and homocysteine formation are regulated by independent mechanisms in C3H/10T1/2 Cl 8 cells. 2) S-Adenosylhomocysteine catabolism was the main source of the homocysteine export induced by cysteamine.
Mol Pharmacol 1990 Sep
PMID:Cysteamine increases homocysteine export and glutathione content by independent mechanisms in C3H/10T1/2 cells. 240 25

Neplanocin A [(-)-9-[trans-2',trans-3'-dihydroxy-4'-(hydroxymethyl)-cyclopent-4 '- enyl]-adenine] and 9-[trans-2',trans-3'-dihydroxycyclopent-4'-enyl]-adenine (1) and -3-deazaadenine (2) are potent inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase (EC 3.3.1.1) in mouse L929 cells. When cells were treated for 15 min with varying concentrations of the drugs, the IC95 values (concentration needed to produce 95% inhibition of AdoHcy hydrolase) for neplanocin A, 1, and 2 were determined to be 0.2 microM, 0.5 microM, and 0.5 microM, respectively. Incubation of L929 cells with 1.0 microM concentrations of neplanocin A, 1, or 2 produced rapid inactivation of AdoHcy hydrolase (within 30 min the enzyme was 95% inhibited), which persisted for at least 72 hr. At lower concentrations (0.032 microM), substantial recovery of AdoHcy hydrolase activity was noted after 48 and 72 hr in cultures treated with neplanocin A but not in cultures treated with 1 or 2. L929 cells treated with neplanocin A, 1 or 2 showed a rapid increase in intracellular levels of AdoHcy (as well as the ratio of AdoHcy/S-adenosylmethionine). Cells treated with neplanocin A also contained significant amounts of S-neplanocylmethionine, whereas cells treated with 1 or 2 showed no evidence of the formation of a similar metabolite. When neplanocin A and adenosine were incubated in cell lysates, rapid conversion to neplanocin D and inosine, respectively, were observed, illustrating the affinity of these nucleosides for cellular adenosine deaminase. In contrast, when 1 and 2 were incubated in cell lysates, no evidence for deamination was observed. These data illustrate that compounds 1 and 2 retain the inhibitory activity of neplanocin A toward cellular AdoHcy hydrolase, producing elevated cellular levels of AdoHcy. However, by removing the 4'-hydroxymethyl group from neplanocin A, analogs 1 and 2 are no longer substrates for adenosine deaminase and adenosine kinase.
Mol Pharmacol 1988 Jun
PMID:Effects of 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-adenine and -3-deazaadenine on the metabolism of S-adenosylhomocysteine in mouse L929 cells. 245 88

Protein methyltransferases, rich in most mammalian brains, were studied in human cerebrospinal fluid (CSF). Among several well-characterized groups of methyltransferases, protein methylase I (S-adenosylmethionine:protein-arginine N-methyltransferase, EC 2.1.1.23) was found in significant amounts in human CSF samples. Both myelin basic protein (MBP) -specific and histone-specific protein methylase I activities were observed, the latter being generally higher in most CSF. S-Adenosyl-L-homocysteine, a potent product inhibitor for the methyltransferase, inhibited approximately 90% of MBP-specific protein methylase I activity at a concentration of 1 mM. The optimum pH of the MBP-specific protein methylase I was found to be around 7.2. Identity of exogenously added MBP as the methylated substrate for CSF enzyme was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. An amino acid analysis of the [methyl-3H]protein hydrolysate showed two major radioactive peaks cochromatographing with monomethyl- and dimethyl (symmetric)-arginine. Human CSF contained relatively high endogenous protein methylase I activity (activity measured without added substrate protein): The endogenous substrate can be immunoprecipitated by antibody raised against calf brain MBP. Finally, CSF from several neurological patients were analyzed for protein methylase I, and the results are presented.
J Mol Neurosci 1989
PMID:Studies on protein methyltransferase in human cerebrospinal fluid. 248 41

The EcoP15 modification methylase gene from the p15B plasmid of Escherichia coli 15T-has been cloned and expressed at high levels in a plasmid vector system. We have purified the enzyme to near homogeneity in large amounts and have studied some of its enzymatic properties. Initial rates of methyl transfer are first order in methylase concentration and, with pUC19 DNA as substrate, the reaction proceeds by a random mechanism in which either DNA or S-adenosylmethionine can bind to the free enzyme. After methyltransfer to DNA, the methylated DNA and S-adenosylhomocysteine appear to dissociate in random order. As expected in such a mechanism, S-adenosylhomocysteine is a non-competitive inhibitor by S-adenosylmethionine at concentrations not much above its KM suggests that release of methylated DNA may be the rate-limiting step. This suggestion is strengthened by the fact that a mutant of the closely related EcoP1 does not show such substrate inhibition.
J Mol Biol 1989 Oct 20
PMID:Cloning, over-expression and the catalytic properties of the EcoP15 modification methylase from Escherichia coli. 258 3

We have used High Performance Liquid Chromatography to determine metabolite characteristics of three recent isolates of Acanthamoeba which exhibit cultural characteristics consistent with those of established potential pathogens. Growing amoebae and dormant cysts of these isolates were explored in regard to their qualitative and quantitative intracellular levels of polyamine and S-adenosylmethionine metabolites. The polyamine found in the greatest concentration in the growing cells was 1,3-diaminopropane (DAP), followed by spermidine (SPD). A low level of putrescine was also found in the growing cells. These polyamines significantly decreased in concentration as the amoebae differentiated to cysts. N8-acetylspermidine and acetylspermine were found in both developmental stages while acetylcadaverine was found only in growing amoebae and N1-acetylspermidine only in cysts. Acetylputrescine was present in both stages of two isolates but only in the growing amoebae of the third isolate. Spermine was not detected in any of the isolates. S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) were present in growing amoebae but SAM was undetectable or barely detectable in cysts. SAH also decreased in concentration during encystation of two of the isolates to a level comparable to that of the other isolate. The developmental transition from growing amoebae to dormant cysts is characterized metabolically by a threshold adjustment in concentration of SAM, SAH and of the polyamines (esp., DAP and SPD).
Mol Cell Biochem 1989 Oct 31
PMID:Comparison of polyamine and S-adenosylmethionine contents of growing and encysted Acanthamoeba isolates. 258 95


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