EFFECTS OF HEMOPEXIN ON HEME-MEDIATED REPRESSION OF 5-AMINOLEVULINATESYNTHASE AND INDUCTION OF HEME OXYGENASE IN CULTURED-HEPATOCYTES

The serum protein hemopexin is considered to have a major role in the mechanism of the uptake of heme by hepatocytes by means of a heme-hemo pexin receptor. Therefore, we examined in primary cultures of adult ra t and embryonic chick hepatocytes whether the presence of hemopexin wo uld affect the heme-medated repression of 5-aminolevulinate synthase a ctivity (the rate-limiting enzyme of heme biosynthesis) and the heme-i nduced increase of heme oxygenase activity (the rate-limiting step of heme degradation). Both of these heme-mediated effects were partly or entirely prevented by the presence of hemopexin. We conclude that homo logous hemopexin, at molar concentrations exceeding that of heme, inhi bited the uptake of heme into hepatocytes. These results suggest that heme, in amounts sufficient to affect the rate-limiting steps of heme synthesis and degradation, can only enter hepatocytes in primary cultu re when the binding capacity of hemopexin for heme has been exceeded o r altered.