9417748 Anderson Most fish remove waste nitrogen (from protein 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 that is stored and excreted periodically in the urine; the metabolic pathway for this conversion is called the urea cycle. One group of fishes, the elasmobranchs (sharks, skates, 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 to prevent the loss of body water. The urea cycle in these species is analogous to that in species that normally excrete urea, but with some significant differences. The enzyme catalyzing the first reaction in the urea cycle is quite unique. Dr. Anderson has determined the structure of the gene that expresses this enzyme in order to pursue the proposed studies in teleost (non-elasmobranch) fishes. This same unique enzyme is found in the early development of some teleost fishes. 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 it is expressed. Dr. Anderson's 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. ***
