The
acute porphyrias in relapse are commonly treated with intravenous
heme infusion to decrease the activity of
delta-aminolevulinic acid synthase, normally the rate-controlling
enzyme in
heme biosynthesis. The biochemical effects of
heme treatment are short-lived, probably due in part to
heme-mediated induction of
heme oxygenase, the rate-controlling
enzyme for
heme degradation. In this work, selected nonheme
metalloporphyrins were screened for their ability to reduce
delta-aminolevulinic acid synthase
mRNA and induce
heme oxygenase mRNA in chick embryo liver cell cultures. Of the
metalloporphyrins tested, only
zinc-mesoporphyrin reduced
delta-aminolevulinic acid synthase
mRNA without increasing
heme oxygenase mRNA. The combination of
zinc-mesoporphyrin and
heme, at nanomolar concentrations, decreased
delta-aminolevulinic acid synthase
mRNA in a dose-dependent manner. The combination of
zinc-mesoporphyrin (50 nM) and
heme (200 nM) decreased the half-life of the
mRNA for
delta-aminolevulinic acid synthase from 5.2 to 2.5 h, while a similar decrease was produced by
heme (10 microM) alone (2.2 h). The ability of
zinc-mesoporphyrin to supplement the reduction of
delta-aminolevulinic acid synthase
mRNA by
heme, in a process similar to that observed with
heme alone, provides a rationale for further investigation of this compound for eventual use as a supplement to
heme therapy of the
acute porphyrias and perhaps other conditions in which
heme may be of benefit.