Work

Inhibition of protohaem ferro-lyase in experimental porphyria. Isolation and partial characterization of a modified porphyrin inhibitor

Year: 1980

Type: article

Abstract: 1. A modified porphyrin with inhibitory activity towards protohaem ferro-lyase was purified from the livers of mice treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine, and partially characterized. 2. The inhibitor can be labelled by 5-amino[4-14C]-laevulinate, suggesting that it originates from pre-labelled liver haem. No radioactivity from 3,5-diethoxycarbonyl-1,4-dihydro[2,6-14C]collidine can be recovered bound to the purified abnormal porphyrin when the radioactive drug is used to induce its formation. 3. Similar modified porphyrins isolated from the livers of animals treated with 2-allyl-2-isopropylacetamide, secobarbitone or 1-ethynylcyclohexanol did not exhibit inhibitory activity toward protohaem ferro-lyase. 4. The inhibition of protohaem ferro-lyase was progressive, could be slowed down by cooling and partially prevented by preincubating the enzyme with the porphyrin substrate. Once established, inhibition could not be reversed by addition of the substrate 5. These results suggest that the modified porphyrin irreversibly inhibits protohaem ferro-lyase and may be used as a sensitive and selective reagent to titrate the number of active centres of the enzyme.

Source: Biochemical Journal

DOI: 10.1042/bj1880145

Authors: F De Matteis, A H Gibbs, T R Tephly

Institutions: University of Iowa, MRC Toxicology Unit, Medical Research Council

Language: English

Topic: Porphyrin Metabolism and Disorders

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funder: Fogarty International Center