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Plasma clearance of intravenously injected aspartate aminotransferase isozymes: Evidence for preferential uptake by sinusoidal liver cells
Author(s) -
Kamimoto Yukio,
Horiuchi Seikoh,
Tanase Sumio,
Morino Yoshimasa
Publication year - 1985
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840050305
Subject(s) - isozyme , endocytosis , clearance rate , medicine , cytosol , endocrinology , biology , clearance , in vitro , hepatocyte , biochemistry , enzyme , chemistry , receptor , urology
Both cytosolic (c‐AAT) and mitochondrial (m‐AAT) isozymes of aspartate aminotransferase (EC 2.6.1.1) appear in serum in some diseases including hepatobiliary dysfunction. The present study aimed at elucidation of the mechanism by which AAT isozymes are cleared from blood. Intravenous injection into rats of m‐AAT and c‐AAT purified from rat liver exhibited a biphasic clearance curve with an overall half‐life of 42 min and 4.7 hr, respectively. The tissue distribution of the radioactivity following intravenous administration of 125 I‐labeled isozymes revealed that the liver is a major organ involved in plasma clearance of these isozymes. This conclusion was also supported by the significant retardation in plasma clearance of m‐AAT in hepatectomized as well as CCI 4 ‐intoxicated rats. Furthermore, clearance rate of each AAT isozyme in an isolated perfused liver exhibited a single exponential process with the uptake rate for m‐AAT being much faster than that for c‐AAT. Separation of hepatocytes and sinusoidal liver cells from the rat intravenously injected with 125 I‐labeled AAT isozymes revealed that sinusoidal cells were responsible for the plasma clearances. In vitro uptake study showed that both isozymes were exclusively taken up by sinusoidal liver cells. The uptake rate for m‐AAT was considerably greater than that for c‐AAT. Endocytotic index for uptake by sinusoidal cells was 16 times with c‐AAT and 34 times with m‐AAT as compared with that for inulin or dextran which are taken up by fluid‐phase endocytosis, suggesting involvement of adsorptive endocytosis in the uptake of the isozymes.