Carbamoyl Phosphate and Energy Metabolism in Elasmobranchs and Other Fish

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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.//