Intrahepatocellular site of the catabolism of heme and globin moiety of hemoglobin-haptoglobin after intravenous administration to rats.
The intracellular site of incorporation and degradation of heme and globin moiety of hemoglobin-haptoglobin in rat liver cells was investigated in vivo. Hemoglobin-haptoglobin, administered intravenously to rats, is cleared from the circulation and incorporated exclusively into liver parenchymal cells through the receptor specific for the molecule (Kino, K., Tsunoo, H., Higa, Y., Takami, M., Hamaguchi, H., and Nakajima, H. (1980) J. Biol. Chem. 255, 9616-9620). Intracellular distribution of radioactivity was determined after intravenous administration of [3H-Heme,14C-Globin]hemoglobin-haptoglobin to rats. The doubly labeled hemoglobin-haptoglobin was incorporated first in organelles of lower anodic mobility in carrier-free electrophoresis and of low density (density range, 1.05-1.07 g/ml) in Percoll density gradient centrifugation recovered in Golgi subfractions of the liver cells in a substantially intact form. In the subsequent stages, these organelles progressively acquired a higher anodic mobility as well as higher density, presumably through fusion with other organelles. In the resulting organelles of higher anodic mobility in electrophoresis and high density (density range, 1.07-1.15 g/ml) in Percoll, the hemoglobin-haptoglobin first dissociated symmetrically into two 82,000-dalton subunits having intact heme, and then the organelles containing only 3H radioactivity but no 14C radioactivity were separated by electrophoresis. Most of the 3H radioactive materials in these organelles are identified as intact [3H]heme. These investigations suggest that the heme moiety of hemoglobin-haptoglobin in the organelles is detached from globin-haptoglobin and binds to another carrier protein prior to conversion of heme to bilirubin.
Oshiro
S
S
Department of Biochemical Genetics, Tokyo Medical and Dental University, Japan.
Nakajima
H
H
D000818:Animals; D002250:Carbon Radioisotopes; D005914:Globins / Q000378:metabolism*; D006242:Haptoglobins / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D012156:Reticulocytes / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014316:Tritium
D002250:Carbon Radioisotopes; D006242:Haptoglobins; D006454:Hemoglobins; D014316:Tritium; D006418:Heme; D005914:Globins