Serum albumin serves as the transport protein for long chain fatty acids, bilirubin, tryptophan, and various hormones and drugs. The question of how albumin delivers these substances to the appropriate target tissue remains unanswered. The long term goal of this project is to identify the structural features of albumin which result in recognition by cell surface receptors and translocation of appropriate albumin-transported substances into or out of cells. The immediate aims of this proposal are to identify sites on albumin for binding of fatty acids and bilirubin, to determine the sites on albumin recognized by hepatocyte receptors and to determine the degree to which the albumin-receptor recognition process is dependent on the presence of specific ligands on albumin. Binding sites on albumin for long chain fatty acids and bilirubin will be identified using radioactive affinity labels. Binding of I125 albumin and its fragments, with or without ligands present, to hepatocytes in suspension will be evaluated quantitatively in terms of numbers of binding sites per cell and equilibrium binding constants. Kinetic uptake of ligands will be assessed to determine how the carrier protein is involved. Uptake patterns for various labeled albumins and fragments carrying different combinations of non-covalently attached ligands will be evaluated for isolated hepatocytes and the perfused liver. The expession of receptors on the hepatocytes will be compared for normal liver and several lines of hepatomas. The results of these studies will lead to a better understanding of the control of targeted transport to normal and pathologic tissue of the many different substances carried by serum albumin.
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| Reed, R G; Davidson, L K; Burrington, C M et al. (1988) Non-resolving jaundice: bilirubin covalently attached to serum albumin circulates with the same metabolic half-life as albumin. Clin Chem 34:1992-4 |
| Reed, R G (1988) Ligand-binding properties of albumin Parklands: Asp365----His. Biochim Biophys Acta 965:114-7 |
