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J. Biol. Chem., Vol. 263, Issue 31, 16032-16038, Nov, 1988
S Oshiro and H Nakajima
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.
Intrahepatocellular site of the catabolism of heme and globin moiety of hemoglobin-haptoglobin after intravenous administration to rats
Department of Biochemical Genetics, Tokyo Medical and Dental University, Japan.
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