The Urea Cycle in Fish

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9727741 Anderson Most fish remove waste nitrogen (from protein and energy metabolism) as ammonia, which diffuses across the gills into the water. This is in contrast to most terrestrial vertebrate animals, which convert ammonia to urea which is stored and excreted periodically in the urine (referred to as "ureotelic" species); the metabolic pathway for this conversion is called the urea cycle. One group of fishes, the clasmobranchs (sharks and rays), synthesize and retain high concentrations of urea in their tissues for the purpose of maintaining an osmotic balance with the high salt concentration in sea water. The urea cycle in these species is analogous to that in ureotelic species, but with some significant differences. Dr. Anderson has determined the structure of the gene that expresses this unique enzyme catalyzing the first metabolic step in the urea cycle. This same unique enzyme is found in some telcost fishes as well, but apparently is absent in most adult species, and he has determined the structure of the gene for the enzyme in several teleost fishes. A surprising finding is that is several teleost species, this enzyme and in some cases, all of the urea cycle enzymes, is expressed primarily in muscle, rather than in liver as expected. The proposed studies will help to establish if the gene for this enzyme of the urea cycle is present in all fish and when and how and why it is expressed. The hypothesis is that this enzyme and the urea cycle are expressed only during embryogenesis (very early development) in most fish. Ammonia toxicity is the number one problem in the aquaculture industry. Understanding the mechanism of how expression of the urea cycle enzymes is regulated in fish may provide an opportunity to genetically modify fish to express the urea cycle and thus increase tolerance to ammonia.