Carbamoyl Phosphate and Energy Metabolism in Elasmobranchs and Other Fish

海洋板鳃动物（鲨鱼、鳐鱼和鳐鱼）在其组织中合成并保留高浓度的尿素，以达到渗透调节的目的。哺乳动物也合成尿素，但其目的是将含氮废物解毒，以尿素的形式在尿液中处理。在鲨鱼肝脏中催化尿素生物合成第一步的酶与哺乳动物中相应的酶有独特的不同，而且它也存在于一些非elasmobranch的鱼类中，这很有趣，因为鱼类通常不制造尿素-它们通过鳃直接将氨排泄到水中。这一反应步骤的产物也被用于基因表达所需的前体的生物合成，该化合物的形成是由一种不同但相关的酶催化的，这种酶在鲨鱼中也不同于相应的哺乳动物酶。这些差异与缺乏大多数肿瘤组织所需的氮和能量的化合物有关，结果可能与鲨鱼对癌症有抵抗力的观察有关。在如何储存脂肪以获取能量以及如何在禁食期间获得能量方面，蓝鳃鱼与其他物种也有很大的不同。本研究将对这些酶和过程进行研究，结果将提供有价值的比较信息：1)这些酶（鲨鱼的酶似乎是进化的中间产物），2)尿素生物合成途径的进化和功能，以及3)鲨鱼和鱼类的能量、氮和碳水化合物代谢的酶调节。这可以作为研究人类或哺乳动物这些过程的有用模型系统

Marine elasmobranchs (sharks, skates, and rays) synthesize and retain high concentrations of urea in their tissues for the purpose of osmoregulation. Mammals also synthesize urea, but for the purpose of detoxifying nitrogen wastes for disposal in the urine as urea. The enzyme catalyzing the first step of urea biosynthesis in liver of sharks is uniquely different from the corresponding enzyme in mammalian species, and it is also present in a few non- elasmobranch species of fish, which is interesting, since fish generally do not make urea - they excrete ammonia directly into the water via their gills. The product of this reaction step is also utilized for biosynthesis of precursors needed for genetic expression, and the formation of this compound is catalyzed by a different but related enzyme, which in sharks is also different from the corresponding mammalian enzyme. These differences are related to the absence of a compound needed by most tumor tissues for nitrogen and energy, and the results may have a bearing on the observation that sharks are resistant to cancer. Elasmobranchs also differ significantly form other species in how they store fat for energy and how this is made available during fasting. These enzymes and processes will be investigated in this study and the results will provide valuable comparative information about 1) these enzymes (the enzymes for shark appear to be evolutionary intermediates), 2) the evolution and function of the urea biosynthetic pathway, and 3) the enzymatic regulation of energy and of nitrogen and carbohydrate metabolism in sharks and fish, which may serve as useful model systems for studying these processes in humans or mammalian species in general.//