Objectives of this pilot proposal are to characterize the biochemical pathways of heme, bile pigment, and sulfite disposal in frogs and other amphibians during maturation and in adulthood and to compare these with the corresponding pathways that have been reported for mammals. A major goal is to determine whether frogs or other common amphibians can swerve as useful experimental models for studying tetrapyrrole and sulfite metabolism in humans and other mammals. These goals will be achieved experimentally by comparative analysis of hepatic enzyme activities and bile pigment composition in the serum and bile of several amphibian species.
Specific aims are: To characterize and quantitate the pigments present in gallbladder and hepatic bile of larval and adult forms of the bullfrog, Rana catesbiana, with emphasis on the major, recently discovered, C-10 sulfonated tetrapyrrole. To investigate the mechanism of formation of sulfonated bile pigments in frogs. To compare and contract the biochemical pathways of heme and bile pigment metabolism in larval and adult frogs with those that have been described for mammals. To determine whether bisulfite addition to biliverdin occurs in common laboratory amphibians other than R. catesbiana and R. pipiens. To compare sulfite oxidase activities in liver of selected mature amphibian species. These studies are related to liver metabolism, liver disease and jaundice in humans and to the toxicological and biochemical effects to sulfite, a common food additive and environmental pollutant. The studies may suggest new approaches for the treatment of familial unconjugated hyperbilirubinemia and the prevention of jaundice in newborn babies.
| Senge, M O; Ma, J S; McDonagh, A F (2001) Sodium etiobilirubin-IVgamma-C10-sulfonate: a highly solvated bile pigment structure containing two different non-ridge-tile conformers in the unit cell. Bioorg Med Chem Lett 11:875-8 |
