Nishimori Isao, Innocenti Alessio, Vullo Daniela, Scozzafava Andrea, Supuran Claudiu T
Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi, Japan.
Bioorg Med Chem. 2007 Nov 1;15(21):6742-7. doi: 10.1016/j.bmc.2007.08.008. Epub 2007 Aug 15.
The first anion inhibition study of the mitochondrial human carbonic anhydrase (hCA, EC 4.2.1.1) isoform hCA VB is reported. Fluoride, chloride, bromide, iodide, cyanate, thiocyanate, cyanide, azide, bicarbonate, carbonate, nitrate, nitrite, hydrogen sulfide, bisulfite, sulfate, sulfamide, sulfamic acid, phenylboronic acid and phenylarsonic acid were compared as inhibitors of the two mitochondrial isozymes hCA VA and hCA VB. These enzymes are involved in biosynthetic reactions leading to fatty acid and Krebs cycle intermediates biosynthesis in addition to acting as catalysts for the interconversion of carbon dioxide and bicarbonate. The anion inhibition profiles of the two isoforms are dramatically different. The best hCA VB inhibitors were cyanate, thiocyanate, cyanide and hydrogensulfide (K(I)s of 80-76 microM) whereas the least effective ones were the halides (K(I)s of 11-72 mM), with the best inhibitor being fluoride and the least effective ones bromide and iodide. Whereas hCA VA is not sensitive to bicarbonate inhibition (K(I) of 82 mM) similarly to the cytosolic isoform hCA II, hCA VB is well inhibited by this anion, with a K(I) of 0.71 mM. Overall, hCA VB is more sensitive to anion inhibitors as compared to hCA VA. Such data support prior suggestions that the two mitochondrial isozymes play different physiological functions.
报道了对线粒体人碳酸酐酶（hCA，EC 4.2.1.1）同工型hCA VB的首次阴离子抑制研究。比较了氟化物、氯化物、溴化物、碘化物、氰酸盐、硫氰酸盐、氰化物、叠氮化物、碳酸氢盐、碳酸盐、硝酸盐、亚硝酸盐、硫化氢、亚硫酸氢盐、硫酸盐、氨磺酰、氨基磺酸、苯硼酸和苯胂酸作为两种线粒体同工酶hCA VA和hCA VB抑制剂的情况。这些酶除了作为二氧化碳和碳酸氢盐相互转化的催化剂外，还参与导致脂肪酸和三羧酸循环中间产物生物合成的生物合成反应。这两种同工型的阴离子抑制谱有显著差异。hCA VB的最佳抑制剂是氰酸盐、硫氰酸盐、氰化物和硫化氢（抑制常数K(I)为80 - 76 μM），而最无效的是卤化物（K(I)为11 - 72 mM），其中最佳抑制剂是氟化物，最无效的是溴化物和碘化物。与胞质同工型hCA II类似，hCA VA对碳酸氢盐抑制不敏感（K(I)为82 mM），而hCA VB则受到该阴离子的良好抑制，K(I)为0.71 mM。总体而言，与hCA VA相比，hCA VB对阴离子抑制剂更敏感。这些数据支持了之前关于这两种线粒体同工酶发挥不同生理功能的观点。
