Carbamoyl Phosphate and Energy Metabolism in Elasmobranchs and Other Fish

海洋弹簧鱼(鲨鱼、溜冰鱼和银鱼)合成并在其组织中保持高浓度的尿素，以达到渗透调节的目的。哺乳动物也合成尿素，但目的是解毒氮废物，以尿素的形式在尿液中处置。鲨鱼肝脏中催化尿素生物合成的第一步的酶与哺乳动物物种中相应的酶是独特的不同，它也存在于一些非棘目鱼类中，这是有趣的，因为鱼通常不制造尿素-它们通过鳃直接将氨排泄到水中。这一反应步骤的产物也用于基因表达所需前体的生物合成，这种化合物的形成是由一种不同但相关的酶催化的，在鲨鱼中，这种酶也不同于相应的哺乳动物酶。这些差异与大多数肿瘤组织缺乏氮和能量所需的化合物有关，结果可能与鲨鱼对癌症具有抵抗力的观察有关。在如何储存能量的脂肪以及如何在禁食期间获得脂肪方面，棘鳃动物也与其他物种有很大的不同。这项研究将对这些酶和过程进行研究，结果将提供关于以下方面的有价值的比较信息：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)鲨鱼和鱼的能量以及氮和碳水化合物代谢的酶调节，它们可以作为有用的模型系统来研究人类或哺乳动物的这些过程。

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.//