Nature of heme metabolizing enzymes in a mutant rat with hyperbilirubinuria

Eisai hyperbilirubinuria rat (EHBR) is a mutant strain which is originated from Sprague Dawley rats. The activities of heme metabolizing enzymes in EHBR were compared with those of Sprague Dawley rats as the control. The activity of delta-aminolevulinic acid (delta-ALA) synthetase, the initial and rate-limiting enzyme in heme biosynthesis, was significantly higher in the liver of EHBR. However, no significant difference in the activity of heme oxygenase, the first and rate-limiting enzyme in heme degradation, was observed in EHBR as compared to control rats. DDC, a porphyrinogenic agent, caused marked and prolonged increase in the activity of delta-ALA synthetase in EHBR. However, the contents of microsomal total heme and cytochrome P-450 were significantly decreased in EHBR 24 hrs after DDC injection. The activity of heme oxygenase by CdCl2, a inducer of heme oxygenase, was considerably higher in EHBR than in control rats. These results indicate some specific hypersensitivity for heme metabolizing enzymes in EHBR.