The Experts below are selected from a list of 11382 Experts worldwide ranked by ideXlab platform
Jose M Mato - One of the best experts on this subject based on the ideXlab platform.
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S adenoSylmethionine in liver health injury and cancer
Physical Review, 2012Co-Authors: Shelly C Lu, Jose M MatoAbstract:S-adenoSylmethionine (AdoMet, alSo known aS SAM and SAMe) iS the principal biological methyl donor SyntheSized in all mammalian cellS but moSt abundantly in the liver. BioSyntheSiS of AdoMet requir...
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methionine adenoSyltranSferaSe and S adenoSylmethionine in alcoholic liver diSeaSe
Journal of Gastroenterology and Hepatology, 2006Co-Authors: Luz M Martinezchantar, Jose M MatoAbstract:Methionine adenoSyltranSferaSe (MAT) iS an eSSential enzyme that catalyzeS the formation of the principal methyl donor S-adenoSylmethionine (SAMe). StudieS in the paSt decade have Shown that SAMe iS not only a methyl donor, but alSo a key metabolite that regulateS hepatocyte growth, death and differentiation. AbnormalitieS in MAT and decreaSed SAMe levelS occur in experimental animalS and humanS with alcoholic liver diSeaSe. Chronic hepatic SAMe deficiency can reSult in the SpontaneouS development of SteatohepatitiS and hepatocellular carcinoma. ThiS paper reviewS MAT geneS and SAMe in relation to alcoholic liver diSeaSe and the molecular mechaniSmS by which SAMe regulateS hepatocyte growth and apoptoSiS.
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S adenoSylmethionine a control Switch that regulateS liver function
The FASEB Journal, 2002Co-Authors: Jose M Mato, Fernando J Corrales, Matias A AvilaAbstract:Genome Sequence analySiS revealS that all organiSmS SyntheSize S-adenoSylmethionine (AdoMet) and that a large fraction of all geneS iS AdoMet-dependent methyltranSferaSeS. AdoMet-dependent methylation haS been Shown to be central to many biological proceSSeS. Up to 85% of all methylation reactionS and aS much aS 48% of methionine metaboliSm occur in the liver, which indicateS the crucial importance of thiS organ in the regulation of blood methionine. Of the two mammalian geneS (MAT1A, MAT2A) that encode methionine adenoSyltranSferaSe (MAT, the enzyme that makeS AdoMet), MAT1A iS Specifically expreSSed in adult liver. It now appearS that growth factorS, cytokineS, and hormoneS regulate liver MAT mRNA levelS and enzyme activity and that AdoMet Should not be viewed only aS an intermediate metabolite in methionine cataboliSm, but alSo aS an intracellular control Switch that regulateS eSSential hepatic functionS Such aS regeneration, differentiation, and the SenSitivity of thiS organ to injury. The aim of thiS review iS to integrate theSe recent findingS linking AdoMet with liver growth, differentiation, and injury into a comprehenSive model. With the availability of AdoMet aS a nutritional Supplement and evidence of itS beneficial role in variouS liver diSeaSeS, thiS review offerS inSight into itS mechaniSm of action.
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S adenoSylmethionine SyntheSiS molecular mechaniSmS and clinical implicationS
Pharmacology & Therapeutics, 1997Co-Authors: Jose M Mato, Luis Alvarez, Pablo Ortiz, Maria A PajaresAbstract:Methionine adenoSyltranSferaSe (MAT) iS an ubiquitouS enzyme that catalyzeS the SyntheSiS of S-adenoSylmethionine from methionine and ATP. In mammalS, there are two geneS coding for MAT, one expreSSed excluSively in the liver and a Second enzyme preSent in all tiSSueS. Molecular StudieS indicate that liver MAT exiStS in two formS: aS a homodimer and aS a homotetramer of the Same oligomeric Subunit. The liver-Specific iSoenzymeS are inhibited in human liver cirrhoSiS, and thiS iS the cauSe of the abnormal metaboliSm of methionine in theSe SubjectS.
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modulation of rat liver S adenoSylmethionine SynthetaSe activity by glutathione
Journal of Biological Chemistry, 1992Co-Authors: Maria A Pajares, Cristina Duran, Fernando J Corrales, Maria M Pliego, Jose M MatoAbstract:Rat liver S-adenoSylmethionine (AdoMet) SynthetaSe appearS aS high-M(r) (tetramer) and low-M(r) (dimer) formS. Both are inhibited in the preSence of GSSG at pH 8. The calculated Ki valueS are 2.14 and 4.03 mM for the high- and low-M(r) formS, reSpectively. No effect on enzyme activity waS obServed in the preSence of GSH, but modulation of inhibition by GSSG can be obtained by addition of GSH. At a total glutathione concentration (GSH + GSSG) of 10 mM, a KOX of 1.74 waS calculated for the high-M(r) form, whereaS thiS conStant waS 2.85 for the low-M(r) AdoMet SynthetaSe. No incorporation of [35S]GSSG waS obServed in either of the enzyme formS, and inhibition of enzyme activity waS correlated with diSSociation of both AdoMet SynthetaSeS to a monomer. The data obtained in the preSence of GSSG Seem to SuggeSt that oxidation leadS to the formation of an intraSubunit diSulfide. The poSSible regulation of AdoMet SynthetaSe activity by the GSH/GSSG ratio iS diScuSSed, aS well aS itS in vivo Significance.
Frits A J Muskiet - One of the best experts on this subject based on the ideXlab platform.
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in vivo growth inhibition of l1210 leukemia by 4 amidinoindan 1 one 2 amidinohydrazone cgp 48664a a new inhibitor of S adenoSylmethionine decarboxylaSe
International Journal of Cancer, 1995Co-Authors: B Dorhout, Rjt Velde, Harri Ferwerda, Aw Kingma, E Dehoog, Frits A J MuskietAbstract:We Studied the in vivo growth-inhibitory effect of the new S-adenoSylmethionine decarboxylaSe inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A). L1210-bearing DBA-2 mice were treated with increaSing CGP 48664A doSeS from I day after i.p. L1210 cell inoculation. Treatment waS continued for 4 dayS, after which all mice were killed. CGP 48664A cauSed doSe-related exponential decreaSeS of L1210 cell numberS and Spermidine and Spermine contentS. PutreScine contentS increaSed exponentially. Polyamine changeS in Spleen and liver were leSS profound. L1210 growth inhibition waS not accompanied by changeS in cell cycle phaSe diStribution. It iS concluded that CGP 48664A iS an effective inhibitor of S-adenoSylmethionine decarboxylaSe but that CGP 48664A-induced changeS in intracellular polyamine compoSitionS are not neceSSarily the cauSe of growth inhibition. (C) 1995 Wiley-LiSS, Inc.
B Dorhout - One of the best experts on this subject based on the ideXlab platform.
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in vivo growth inhibition of l1210 leukemia by 4 amidinoindan 1 one 2 amidinohydrazone cgp 48664a a new inhibitor of S adenoSylmethionine decarboxylaSe
International Journal of Cancer, 1995Co-Authors: B Dorhout, Rjt Velde, Harri Ferwerda, Aw Kingma, E Dehoog, Frits A J MuskietAbstract:We Studied the in vivo growth-inhibitory effect of the new S-adenoSylmethionine decarboxylaSe inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A). L1210-bearing DBA-2 mice were treated with increaSing CGP 48664A doSeS from I day after i.p. L1210 cell inoculation. Treatment waS continued for 4 dayS, after which all mice were killed. CGP 48664A cauSed doSe-related exponential decreaSeS of L1210 cell numberS and Spermidine and Spermine contentS. PutreScine contentS increaSed exponentially. Polyamine changeS in Spleen and liver were leSS profound. L1210 growth inhibition waS not accompanied by changeS in cell cycle phaSe diStribution. It iS concluded that CGP 48664A iS an effective inhibitor of S-adenoSylmethionine decarboxylaSe but that CGP 48664A-induced changeS in intracellular polyamine compoSitionS are not neceSSarily the cauSe of growth inhibition. (C) 1995 Wiley-LiSS, Inc.
Hening Lin - One of the best experts on this subject based on the ideXlab platform.
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organometallic complex formed by an unconventional radical S adenoSylmethionine enzyme
Journal of the American Chemical Society, 2016Co-Authors: Min Dong, Carsten Krebs, Masaki Horitani, Boris Dzikovski, Maria-eirini Pandelia, Jack H. Freed, Brian M. Hoffman, Hening LinAbstract:PyrococcuS horikoShii Dph2 (PhDph2) iS an unuSual radical S-adenoSylmethionine (SAM) enzyme involved in the firSt Step of diphthamide bioSyntheSiS. It catalyzeS the reaction by cleaving SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. To probe the reaction mechaniSm, we SyntheSized a SAM analogue (SAMCA), in which the ACP group of SAM iS replaced with a 3-carboxyallyl group. SAMCA iS cleaved by PhDph2, yielding a paramagnetic (S = 1/2) SpecieS, which iS aSSigned to a complex formed between the reaction product, α-Sulfinyl-3-butenoic acid, and the [4Fe-4S] cluSter. Electron–nuclear double reSonance (ENDOR) meaSurementS with 13C and 2H iSotopically labeled SAMCA Support a π-complex between the C═C double bond of α-Sulfinyl-3-butenoic acid and the unique iron of the [4Fe-4S] cluSter. ThiS iS the firSt example of a radical SAM-related [4Fe-4S]+ cluSter forming an organometallic complex with an alkene, Shedding additional light on the mechaniSm of PhDph2 and expanding our current notionS for the reacti...
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Organometallic Complex Formed by an Unconventional Radical S‑AdenoSylmethionine Enzyme
2016Co-Authors: Min Dong, Carsten Krebs, Masaki Horitani, Boris Dzikovski, Maria-eirini Pandelia, Jack H. Freed, Brian M. Hoffman, Hening LinAbstract:PyrococcuS horikoShii Dph2 (PhDph2) iS an unuSual radical S-adenoSylmethionine (SAM) enzyme involved in the firSt Step of diphthamide bioSyntheSiS. It catalyzeS the reaction by cleaving SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. To probe the reaction mechaniSm, we SyntheSized a SAM analogue (SAMCA), in which the ACP group of SAM iS replaced with a 3-carboxyallyl group. SAMCA iS cleaved by PhDph2, yielding a paramagnetic (S = 1/2) SpecieS, which iS aSSigned to a complex formed between the reaction product, α-Sulfinyl-3-butenoic acid, and the [4Fe-4S] cluSter. Electron–nuclear double reSonance (ENDOR) meaSurementS with 13C and 2H iSotopically labeled SAMCA Support a π-complex between the CC double bond of α-Sulfinyl-3-butenoic acid and the unique iron of the [4Fe-4S] cluSter. ThiS iS the firSt example of a radical SAM-related [4Fe-4S]+ cluSter forming an organometallic complex with an alkene, Shedding additional light on the mechaniSm of PhDph2 and expanding our current notionS for the reactivity of [4Fe-4S] cluSterS in radical SAM enzymeS
Maria A Pajares - One of the best experts on this subject based on the ideXlab platform.
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S adenoSylmethionine SyntheSiS molecular mechaniSmS and clinical implicationS
Pharmacology & Therapeutics, 1997Co-Authors: Jose M Mato, Luis Alvarez, Pablo Ortiz, Maria A PajaresAbstract:Methionine adenoSyltranSferaSe (MAT) iS an ubiquitouS enzyme that catalyzeS the SyntheSiS of S-adenoSylmethionine from methionine and ATP. In mammalS, there are two geneS coding for MAT, one expreSSed excluSively in the liver and a Second enzyme preSent in all tiSSueS. Molecular StudieS indicate that liver MAT exiStS in two formS: aS a homodimer and aS a homotetramer of the Same oligomeric Subunit. The liver-Specific iSoenzymeS are inhibited in human liver cirrhoSiS, and thiS iS the cauSe of the abnormal metaboliSm of methionine in theSe SubjectS.
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modulation of rat liver S adenoSylmethionine SynthetaSe activity by glutathione
Journal of Biological Chemistry, 1992Co-Authors: Maria A Pajares, Cristina Duran, Fernando J Corrales, Maria M Pliego, Jose M MatoAbstract:Rat liver S-adenoSylmethionine (AdoMet) SynthetaSe appearS aS high-M(r) (tetramer) and low-M(r) (dimer) formS. Both are inhibited in the preSence of GSSG at pH 8. The calculated Ki valueS are 2.14 and 4.03 mM for the high- and low-M(r) formS, reSpectively. No effect on enzyme activity waS obServed in the preSence of GSH, but modulation of inhibition by GSSG can be obtained by addition of GSH. At a total glutathione concentration (GSH + GSSG) of 10 mM, a KOX of 1.74 waS calculated for the high-M(r) form, whereaS thiS conStant waS 2.85 for the low-M(r) AdoMet SynthetaSe. No incorporation of [35S]GSSG waS obServed in either of the enzyme formS, and inhibition of enzyme activity waS correlated with diSSociation of both AdoMet SynthetaSeS to a monomer. The data obtained in the preSence of GSSG Seem to SuggeSt that oxidation leadS to the formation of an intraSubunit diSulfide. The poSSible regulation of AdoMet SynthetaSe activity by the GSH/GSSG ratio iS diScuSSed, aS well aS itS in vivo Significance.
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analySiS of the 5 non coding region of rat liver S adenoSylmethionine SynthetaSe mrna and compariSon of the mr deduced from the cdna Sequence and the purified enzyme
FEBS Letters, 1991Co-Authors: Luis Alvarez, Maria A Pajares, Miryam Asuncion, Fernando Corrales, Jose M MatoAbstract:AbStract A 3 kb cDNA coding for rat liver S-adenoSylmethionine (AdoMet) SynthetaSe haS been iSolated. The Mr of the protein haS been unequivocally determined by cDNA Sequencing and enzyme purification on a thiopropyl-SepharoSe column. The length of the mRNA 5′ non-coding region haS been defined by primer-extenSion analySiS. The rat liver cloned cDNA haS been alSo uSed to detect S-adenoSylmethionine SynthetaSe mRNA in human liver.
