Carbonic anhydrase hydrates carbon dioxide (plasma membrane)

Carbonic anhydrase IV (CA4, Zhu and Sly 1990, Okuyama et al. 1992, Baird et al. 1997, Innocenti et al. 2004), carbonic anhydrase IX (CA9, Wingo et al. 2001, Hilvo et al. 2008), carbonic anhydrase XII (CA12, Ulmasov et al. 2000, Pastorekova et al. 2008), and carbonic anhydrase XIV (CA14Ozensoy et al. 2005, Temperini et al. 2008) are membrane-bound enzymes that hydrate extracellular carbon dioxide to yield bicarbonate and a proton.Carbonic anhydrase deprotonates water to yield a zinc-hydroxyl group and a proton which is transferred to external buffer molecules via histidine or glutamate residues in carbonic anhydrase. The hydroxyl group reacts with carbon dioxide in the active site to yield bicarbonate. A water molecule displaces the bicarbonate and the reaction cycle begins again (reviewed in Lindskog 1997). Depending on the concentrations of reactants the reaction is reversible.<br>CA4 has high catalytic activity. CA9, CA12, and CA14 have moderate activity. CA4 is anchored to the extracellular face of the plasma membrane by glycosylphosphatidylinositol. CA9, CA12, and CA14 are single-pass transmembrane proteins. CA4 is found on the extracellular face of capillaries in kidney, lung, and muscle where it maintains the gradient of carbon dioxide between tissue and blood. CA9 and CA12 are found on basolateral membranes of epithelia. CA9 is inducible by Hypoxia-inducible factor 1 alpha (HIF1alpha) and acidifies the extracellular environment of tumors. In rodents CA15 is membrane anchored and has low activity; in primates CA15 is a pseudogene.

碳酸酐酶IV（CA4，Zhu和Sly 1990，Okuyama等1992，Baird等1997，Innocenti等2004），碳酸酐酶IX（CA9，Wingo等2001，Hilvo等2008），碳酸酐酶XII（CA12，Ulmasov等2000，Pastorekova等2008）以及碳酸酐酶XIV（CA14，Ozensoy等2005，Temperini等2008）均为膜结合酶，它们通过水合细胞外二氧化碳生成碳酸氢盐和质子。碳酸酐酶通过去质子化水生成锌-羟基团和质子，该质子通过碳酸酐酶中的组氨酸或谷氨酸残基转移到外部缓冲分子。羟基团与活性位点中的二氧化碳反应生成碳酸氢盐。水分子取代碳酸氢盐，反应周期再次启动（见Lindskog 1997综述）。根据反应物浓度的不同，该反应可逆。<br>CA4具有高催化活性。CA9、CA12和CA14具有中等活性。CA4通过糖基磷脂酰肌醇锚定于质膜的外表面。CA9、CA12和CA14为单跨膜蛋白。CA4存在于肾脏、肺和肌肉的毛细血管外表面，维持组织与血液之间二氧化碳的梯度。CA9和CA12存在于上皮细胞的基底侧膜上。CA9可被低氧诱导因子1α（HIF1α）诱导，并酸化肿瘤的细胞外环境。在啮齿动物中，CA15为膜锚定且活性低；在灵长类动物中，CA15为假基因。