000056743 001__ 56743
000056743 005__ 20200221144216.0
000056743 0247_ $$2doi$$a10.1371/journal.pone.0159002
000056743 0248_ $$2sideral$$a95999
000056743 037__ $$aART-2016-95999
000056743 041__ $$aeng
000056743 100__ $$aHidalgo, J.
000056743 245__ $$aInhibition of pig phosphoenolpyruvate carboxykinase isoenzymes by 3-Mercaptopicolinic acid and novel inhibitors
000056743 260__ $$c2016
000056743 5060_ $$aAccess copy available to the general public$$fUnrestricted
000056743 5203_ $$aThere exist two isoforms of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in pig populations that differ in a single amino acid (Met139Leu). The isoenzymes have different kinetic properties, affecting more strongly the Km and Vmax of nucleotides. They are associated to different phenotypes modifying traits of considerable economic interest. In this work we use inhibitors of phosphoenolpyruvate carboxykinase activity to search for further differences between these isoenzymes. On the one hand we have used the well-known inhibitor 3-mercaptopicolinic acid. Its inhibition patterns were the same for both isoenzymes: a three-fold decrease of the Ki values for GTP in 139Met and 139Leu (273 and 873 µM, respectively). On the other hand, through screening of a chemical library we have found two novel compounds with inhibitory effects of a similar magnitude to that of 3-mercaptopicolinic acid but with less solubility and specificity. One of these novel compounds, (N''1-({5-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]-2-thienyl}methylidene)-2, 4-dichlorobenzene-1-carbohydrazide), exhibited significantly different inhibitory effects on either isoenzyme: it enhanced threefold the apparent Km value for GTP in 139Met, whereas in 139Leu, it reduced it from 99 to 69 µM. The finding of those significant differences in the binding of GTP reinforces the hypothesis that the Met139Leu substitution affects strongly the nucleotide binding site of PEPCK-C.
000056743 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/BIO2014-57314-REDT$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P$$9info:eu-repo/grantAgreement/ES/MINECO/AGL2008-01487ALI$$9info:eu-repo/grantAgreement/ES/DGA/PI078-08$$9info:eu-repo/grantAgreement/ES/DGA/FITE-2012-2013
000056743 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000056743 590__ $$a2.806$$b2016
000056743 591__ $$aMULTIDISCIPLINARY SCIENCES$$b15 / 63 = 0.238$$c2016$$dQ1$$eT1
000056743 592__ $$a1.236$$b2016
000056743 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2016$$dQ1
000056743 593__ $$aMedicine (miscellaneous)$$c2016$$dQ1
000056743 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2016$$dQ1
000056743 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000056743 700__ $$0(orcid)0000-0002-6794-3535$$aLatorre, P.$$uUniversidad de Zaragoza
000056743 700__ $$0(orcid)0000-0003-0062-1029$$aCarrodeguas, J.A.$$uUniversidad de Zaragoza
000056743 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, A.$$uUniversidad de Zaragoza
000056743 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, J.$$uUniversidad de Zaragoza
000056743 700__ $$0(orcid)0000-0001-5992-2913$$aLópez-Buesa, P.$$uUniversidad de Zaragoza
000056743 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000056743 7102_ $$12008$$2780$$aUniversidad de Zaragoza$$bDpto. Produc.Animal Cienc.Ali.$$cÁrea Tecnología de Alimentos
000056743 773__ $$g11, 7 (2016), 0159002[17 pp.]$$pPLoS One$$tPloS one$$x1932-6203
000056743 8564_ $$s2171091$$uhttps://zaguan.unizar.es/record/56743/files/texto_completo.pdf$$yVersión publicada
000056743 8564_ $$s104520$$uhttps://zaguan.unizar.es/record/56743/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000056743 909CO $$ooai:zaguan.unizar.es:56743$$particulos$$pdriver
000056743 951__ $$a2020-02-21-13:13:14
000056743 980__ $$aARTICLE