Abstract

The effects of griseofulvin and 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) on ferrochelatase activity were compared in the 17-day-old chick embryo. While DDC reduced enzyme activity markedly, griseofulvin did not exert an inhibitory effect. These results are consistent with the fact that DDC, but not griseofulvin, causes hepatic porphyrin accumulation in this species. The effects of griseofulvin and DDC on ferrochelatase activity were compared in chick embryo liver cell culture. DDC reduced ferrochelatase activity markedly while griseofulvin caused no significant inhibition. Both DDC and griseofulvin cause marked porphyrin accumulation in this system. The porphyrins were separated and quantitated using high-performance liquid chromatography. Protoporphyrin was the major porphyrin which accumulated in response to DDC, a result consistent with the inhibition of ferrochelatase. In contrast, protoporphyrin was a minor porphyrin accumulating in response to griseofulvin, a result consistent with the failure of griseofulvin to inhibit ferrochelatase; in this case, coproporphyrin was the major porphyrin to accumulate. These findings in the chick embryo contrast with those reported in rodents, where both DDC and griseofulvin exert an inhibitory effect on ferrochelatase. Clearly, species differences exist in the effects of griseofulvin on the enzymes of the heme biosynthetic pathway.