title: Carbonic anhydrase activators: an activation study of the human mitochondrial isoforms VA and VB with amino acids and amines.
abstract: The mitochondrial isozymes of human carbonic anhydrase (hCA, EC 4.2.1.1), hCA VA and hCA VB, were investigated for activation with a series of amino acids and amines. D-His, L-DOPA, histamine, dopamine, and 4-(2-aminoethyl)morpholine were excellent hCA VA activators, with KAs in the range of 10-130 nM. Good hCA VB activating effects were identified for L-His, D-Phe, D-DOPA, L-Trp, L-Tyr, serotonin, and 2-(2-aminoethyl)-pyridine, with KAs in the range of 44-110 nM. All these activators enhanced kcat, having no effect on KM, favoring thus the rate-determining step in the catalytic cycle, the proton transfer reactions between the active site and environment. The activation pattern of the two mitochondrial isoforms is very different from each other and as compared to those of the cytosolic isoforms hCA I and II.
authors.affiliation: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Isao
authors.initials: I
authors.lastname: Nishimori
authors.forename: Alessio
authors.initials: A
authors.lastname: Innocenti
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000588:Amines / Q000494:pharmacology*; D000596:Amino Acids / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects* / Q000378:metabolism; D002384:Catalysis; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D024101:Mitochondrial Proteins / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000596:Amino Acids; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; D002256:Carbonic Anhydrases