Cincinelli Alessandra, Martellini Tania, Vullo Daniela, Supuran Claudiu T
Università degli Studi di Firenze, Dipartimento di Chimica Ugo Schiff, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
Università degli Studi di Firenze, Dipartimento di Chimica Ugo Schiff, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy; Università degli Studi di Firenze, Polo Scientifico, Dipartimento NEUROFARBA;Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy.
Bioorg Med Chem Lett. 2015 Dec 1;25(23):5485-9. doi: 10.1016/j.bmcl.2015.10.074. Epub 2015 Oct 26.
An α-carbonic anhydrase (CA, EC 4.2.1.1) has been purified from the Antarctic hemoglobinless fish Chionodraco hamatus (icefish). The new enzyme, denominated ChaCA, has a good catalytic activity for the physiologic CO2 hydration to bicarbonate reaction, similar to that of the low activity human isoform hCA I, with a kcat of 5.3×10(5) s(-1), and a kcat/Km of 3.7×10(7) M(-1) s(-1). The enzyme was inhibited in the submillimolar range by most inorganic anions (cyanate, thiocyanate, cyanide, bicarbonate, halides), whereas sulfamide, sulfamate, phenylboronic/phenylarsonic acids were micromolar inhibitors, with KIs in the range of 9-77 μM. Many clinically used drugs, such as acetazolamide, methazolamide, dorzolamide, brinzolamide, topiramate and benzolamide were low nanomolar inhibitors, with KIs in the range of 39.1-77.6 nM. As the physiology of CO2/bicarbonate transport or the Root effect in this Antarctic fish are poorly understood at this moment, such inhibition data may give a more detailed insight in the role that CAs play in these phenomena, by the use of inhibitors described here as physiologic tools.
已从南极无血红蛋白鱼类裸头冰鱼（Chionodraco hamatus）中纯化出一种α-碳酸酐酶（CA，EC 4.2.1.1）。这种新酶命名为ChaCA，对生理状态下二氧化碳水合生成碳酸氢盐的反应具有良好的催化活性，类似于低活性的人类同工型hCA I，其催化常数kcat为5.3×10⁵ s⁻¹，催化常数与米氏常数之比kcat/Km为3.7×10⁷ M⁻¹ s⁻¹。该酶受到大多数无机阴离子（氰酸盐、硫氰酸盐、氰化物、碳酸氢盐、卤化物）在亚毫摩尔范围内的抑制，而磺胺、氨基磺酸、苯硼酸/苯胂酸是微摩尔级别的抑制剂，抑制常数KIs在9 - 77 μM范围内。许多临床使用的药物，如乙酰唑胺、甲醋唑胺、多佐胺、布林佐胺、托吡酯和苯甲酰胺是低纳摩尔级别的抑制剂，抑制常数KIs在39.1 - 77.6 nM范围内。由于目前对这种南极鱼类中二氧化碳/碳酸氢盐转运的生理学或鲁特效应了解甚少，通过使用此处描述的抑制剂作为生理学工具，这些抑制数据可能会更详细地揭示碳酸酐酶在这些现象中所起的作用。
