title: Carbonic anhydrase activators: activation of the human isoforms VII (cytosolic) and XIV (transmembrane) with amino acids and amines.
abstract: An activation study of the human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes VII and XIV using a small library of natural/non-natural amino acids and aromatic/heterocyclic amines is reported. hCA VII was efficiently activated by L-/D-His, dopamine and serotonin (K(A)s of 0.71-0.93 microM). The best hCA XIV activators were histamine (K(A) of 10 nM), L-Phe, L-/D-His and 4-amino-L-Phe (K(A)s of 0.24-2.90 microM). In view of the significant expression levels of CA VII and CA XIV in the brain, selective activation of these isoforms may be useful when developing pharmacologic agents for the management of major disorders such as epilepsy and Alzheimer's disease.
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: Alessio
authors.initials: A
authors.lastname: Innocenti
authors.forename: Isao
authors.initials: I
authors.lastname: Nishimori
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Kai
authors.initials: K
authors.lastname: Kaila
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000588:Amines / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D000588:Amines; D000596:Amino Acids; D020536:Enzyme Activators; D007527:Isoenzymes; D002256:Carbonic Anhydrases