Carbonic Anhydrase and the Evolution of Cellular CO2 Transport

小行星9304844 碳酸酐酶（CA）催化CO2的可逆水合/脱水，多年来已知其在CO2的系统转运和排泄中起作用。 然而，最近的研究表明， CO2运输发生在细胞水平（即，穿过单个膜的扩散）。 CA位于膜的“上游”侧，通过HCO 3-的催化脱水促进CO2传输，在边界层中保持高PCO 2，从而驱动CO2扩散穿过膜。 因此，代谢活性组织内的Ca（即，肌肉）对于CO2从细胞内室转运到血液的初始步骤是重要的。 虽然这一过程已经在哺乳动物系统中进行了研究，但对于进化上更原始的生物体来说，信息是完全空白的。 这是我们对CO2运输进化和CA功能进化的理解中的一个主要空白，因为代谢活跃的收缩组织（肌肉）在复杂呼吸系统发展之前很久就进化了。 因此，Ca在代谢活性组织中的进化起源是为了细胞内CO2的消除，这是非常合理的。 这一假设将在一些无脊椎动物物种中进行测试，使用生物化学，生理学，药理学和组织化学技术的组合。 如果在无脊椎动物中发现对这一想法的广泛支持，它将形成一个潜在的统一假设的基础，即细胞CA功能的起源和酶在代谢活性组织中的几乎普遍分布。 这些实验也将形成数据库，在此基础上，未来将设计和执行对更原始生物体的实验。 ***

9304844 Henry The enzyme carbonic anhydrase (CA), which catalyses the reversible hydration/dehydration of CO2 has been known for many years to function in the systemic transport and excretion of CO2. Recent work, however, has shown that the limiting step in CO2 transport occurs at the cellular level (i.e., diffusion across individual membranes). CA, localized on the "upstream" side of the membrane, facilitates CO2 transport via the catalyzed dehydration of HCO3-, maintaining a high PCO2 in the boundary layer and thus driving CO2 diffusion across the membrane. Therefore, Ca within metabolically active tissue (i.e., muscle) is important for the initial step of CO2 transport form the intracellular compartment to the blood. While this process has been studied in mammalian systems, there is a complete void of information for evolutionarily more primitive organisms. This is a major gap in our understanding of both the evolution of CO2 transport and the evolution of CA function, because metabolically active, contractile tissue (muscle) evolved long before the development of complex respiratory systems. It is quite plausible, therefore, for Ca to have had its evolutionary origins in metabolically active tissue for the purpose of cellular CO2 elimination. This hypothesis will be tested in a number of invertebrate species using a combination of biochemical, physiological, pharmacological, and histochemical techniques. If widespread support for this idea is found among the invertebrates, it will form the basis for a potentially unifying hypothesis for the origin of cellular CA function and the near universal distribution of the enzyme in metabolically active tissues. These experiments will also form the database upon which future experiments on even more primitive organisms will be designed and performed. ***