Studies on the biosynthesis production of bilirubin-C14: an improved method utilizing delta-aminolevulinic acid-4-C14 in dogs.

Abstract

Abstract The production of bilirubin-C 14 of high specific activity is desirable for various metabolic studies. Previous methods have utilised glycine-2-C 14 as an isotopic precursor of heme and bilirubin in animals with rapid rates of erythropoiesis. In the current studies a more specific isotopic precursor of heme, δ-aminolevulinic acid-4-C 14 (δ-ALA-C 14 ), was given intravenously to normal dogs with bile fistulas. Approximately 27 per cent of the injected δ-ALA-C 14 was found in bile bilirubin-C 14 in a 72 hour collection, and more than half of this was excreted within the first 4 hours. For comparison, previous studies have shown that in a normal dog less than 0.1 per cent of the injected dose of isotopic glycine is incorporated into bile bilirubin-C 14 in a 72 hour collection and only 0.32 per cent after extensive phlebotomy. In an effort to increase the specific activity of bilirubin-C 14 as much as possible, studies were performed in which δ-ALA-C 14 was injected directly into the portal venous system or given orally, and the specific activity was compared to that obtained after injection of the isotope into a peripheral vein. In addition, studies were performed in animals with increased and decreased rates of erythropoiesis. It was found that no significant increase in the bile bilirubin-C 14 specific activity could be achieved by any of these maneuvers.