U.S.-Norway Cooperative Research: Compartmental Modeling ofthe Metabolism of Retinol and Retinol-Binding Protein

This award will enable Dr. Michael H. Green to collaborate with Drs. Kaare R. Norum, Rune Blomhoff, and Trond Berg, University of Oslo, Norway. They will study the metabolism of vitamin A and will apply the unique approach of computer-assisted, model-based compartmental analysis to data on (1) the in vivo turnover of retinol and retinol-binding protein (RBP) in vitamin A - sufficient rats, (2) the dynamics of intracellular transport and secretion of retinol in vitamin A - deficient rats, and (3) the kinetics of receptor-mediated endocytosis of retinol/RBP in parenchymal and stellate rat liver cells. Their studies will facilitate the development and quantification of physiologically relevant compartmental models which describe the dynamics of whole body and hepatic retinol and RBP metabolism. They will gain information on (1) the nature and extent of RBP vs. retinol recycling among plasma, liver, and extrahepatic tissues, (2) the hepatic regulatory pathways which are affected by vitamin A deficiency, and (3) the intracellular and subcellular transport of retinol and RBP in hepatic cells in vitro. The proposed experiments are a continuation and extension of their previous successful research collaboration. Dr. Green is an expert in analytical methods for vitamin A, model-based compartmental analysis, and whole body vitamin A metabolism. The Norwegian researchers are specially skilled in receptor-mediated endocytosis, liver cell separation and culture, and vitamin A metabolism and methods.