About this Biochemistry, Genetics and Molecular Biology article

Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with carboxylates by Alessio Innocenti; Daniela Vullo; Andrea Scozzafava; Joseph R. Casey; ClaudiuT. Supuran is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

A detailed inhibition study of five carbonic anhydrase (CA, EC 4.2.1.1) isozymes with carboxylates including aliphatic (formate, acetate), dicarboxylic (oxalate, malonate), hydroxy/keto acids (L L-lactate, L L-malate, pyruvate), tricarboxylic (citrate), or aromatic (benzoate, tetrafluorobenzoate) representatives, some of which are important intermediates in the Krebs cycle, is presented. The cytosolic isozyme hCA I was strongly activated by acetate, oxalate, pyruvate, L L-lactate, and citrate (K A around 0.1 lM), whereas formate, malonate, malate, and benzoate were weaker activators (K A in the range 0.1-1 mM). The cytosolic isozyme hCA II was weakly inhibited by all the investigated anions, with inhibition constants in the range of 0.03-24 mM. The membrane-associated isozyme hCA IV was the most sensitive to inhibition by carboxylates, showing a K I of 99 nM for citrate and oxalate, of 2.8 lM for malonate and of 14.5 lM for pyruvate among others. The mitochondrial isozyme hCA V was weakly inhibited by all these carboxylates (K I s in the range of 1.67-25.9 mM), with the best inhibitor being citrate (K I of 1.67 mM), whereas this is the most resistant CA isozyme to pyruvate inhibiti

Author

Alessio Innocenti; Daniela Vullo; Andrea Scozzafava; Joseph R. Casey; ClaudiuT. Supuran

Publisher

Elsevier Science; Elsevier ; Elsevier Ltd.; Elsevier BV (ISSN 0960-894X)

Published

2005

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)