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The excessive induction of hepatic delta-aminolevulinic acid synthetase in rats after the administration of porphyria-inducing compounds is prevented by prior treatment with phenobarbital. Studies in vivo and in vitro indicate that phenobarbital prevents the induction of chemical porphyria by increasing the rate of detoxification of inducers by way of drug-metabolizing enzymes of the hepatic endoplasmic reticulum.

Excessive induction of delta-aminolevulinic acid synthetase in rats after treatment with porphyria-inducing chemicals, such as allylisopropylacetamide, is accompanied by a decrease in microsomal heme and cytochrome P450 concentrations. Measurement of the radioactive decay after labeling of the heme moiety of submicrosomal particles shows increased breakdown of heme in rats treated with allylisopropylacetamide. The effects of allylisopropylacetamide on heme synthesis and heme turnover may be interrelated

Reciprocal control mechanisms between hemoprotein and 8-aminolevulinic acid synthetase take part in coordinate synthesis of the heme and apoenzyme moieties of tryptophan pyrrolase. Stimulation of heme biosynthesis increases tryptophan pyrrolase, whereas enhancement of heme binding by apotryptophan pyrrolase secondarily increases the formation of delta-aminolevulinic acid synthetase, the rate-limiting enzyme in heme formation. Tryptophan-mediated induction of delta-aminolevulinic acid synthetase suggests that heme participates in repression of that enzyme