Carbonic Anhydrase and the Evolution of Cellular CO2 Transport

碳酸酐酶（CA）是一种催化二氧化碳可逆水合/脱水的酶，多年来一直被认为在二氧化碳的全身运输和排泄中起作用。然而，最近的研究表明，二氧化碳运输的限制步骤发生在细胞水平（即跨单个膜的扩散）。CA位于膜的“上游”侧，通过催化HCO3-脱水促进CO2的运输，维持边界层中较高的CO2分压，从而驱动CO2在膜上的扩散。因此，代谢活跃组织（即肌肉）内的钙对于二氧化碳从细胞内转运到血液的第一步是重要的。虽然这一过程已经在哺乳动物系统中进行了研究，但在进化上更原始的生物中却完全缺乏相关信息。这是我们对二氧化碳运输进化和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）早在复杂呼吸系统的发展之前就已经进化了。因此，钙的进化起源于代谢活跃的组织，目的是消除细胞中的二氧化碳，这是相当合理的。这一假设将在许多无脊椎动物物种中使用生化、生理学、药理学和组织化学技术进行测试。如果这一观点在无脊椎动物中得到广泛支持，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跃组织中的几乎普遍分布。这些实验也将形成一个数据库，在此基础上，未来对更原始的生物进行的实验将被设计和进行。＊＊＊

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. ***