Invertebrate Carbonic Anhydrase: A Central Respiratory and Metabolic Enzyme

碳酸酐酶（CA）催化二氧化碳的可逆水合作用形成碳酸氢盐离子和氢离子，可能在许多不同的生理生化过程中发挥重要作用，这些过程涉及分子和离子物种二氧化碳：二氧化碳的运输和排泄，运动后糖异生的二氧化碳固定，以及HCO3-并入氨甲酰磷酸合成尿素。在哺乳动物/脊椎动物系统中，对CA的假定多重功能只进行了粗略的研究，而在无脊椎动物系统中则完全没有。本研究的目的是研究鳃膜相关CA在呼吸应激条件下（如运动和从水呼吸到空气呼吸的转变）甲壳类动物二氧化碳排泄中的作用。线粒体CA也将被研究其在向负责糖异生和尿素合成的代谢途径提供HCO3-方面的潜在作用。生物化学、生理和药理学技术的结合将用于研究原始系统中CA的分布和功能。主要目标将是确定CA是否在各种各样的原始生物中对许多不同的生物过程起核心作用。这项工作将为原始系统中CA功能的起源和进化以及细胞代谢途径的组织模式提供新的有用信息。

The enzyme, carbonic anhydrase (CA), which catalyses the reversable hydration of CO2 to form bicarbonate ions and hydrogen ions, can potentially play an important role in a number of varied physiological and biochemical processes which involve the molecular and ionic species CO2 : CO2 transport and excretion, CO2 fixation for post-exercise gluconeogenesis, and HCO3- incorporation into carbamoyl phosphate for urea synthesis. Putative multiple function of CA have been studied only sketchily in mammalian/vertebrate systems and not at all among the invertebrates. The purpose of this proposed research is to investigate the role of branchial membrane-associated CA in CO2 excretion in crustaceans under conditions of respiratory stress (e.g., exercise and the transition from water-to air-breathing). Mitochondrial CA will also be investigated with respect to its potential role in supplying HCO3- to the metabolic pathways responsible for gluconeogenesis and urea synthesis. A combination of biochemical, physiological and pharmacological techniques will be used to study CA distribution and function in primitive systems. The major objectives will be to determine whether or not CA is central to a number of different biological processes in a wide variety of primitive organisms. This work should provide new and useful information on the origins and evolution of CA function and on the pattern of organization of cellular metabolic pathways in primitive systems.