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Sensitivity of human tissue heme oxygenase to a new synthetic metalloporphyrin
Author(s) -
Chernick Richard J.,
Martasek Pavel,
Levere Richard D.,
Margreiter Raimund,
Abraham Nader G.
Publication year - 1989
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840100320
Subject(s) - heme oxygenase , heme , chemistry , protoporphyrin , bilirubin , zinc protoporphyrin , biochemistry , oxygenase , enzyme , porphyrin , endocrinology , biology
Heme oxygenase, the rate‐limiting enzyme for heme degradation, can be inhibited by several new synthetic metalloporphyrins. Under certain conditions, a depression in heme oxygenase activity has important clinical significance in the treatment of hyperbilirubinemia, and, in this regard, tin‐protoporphyrin has been shown to decrease the production of bilirubin in vitro as well as in vivo . Similarly, our study was concerned with finding a new metalloporphyrin which will inhibit heme oxygenase. Many of the synthetic heme analogs that we analyzed were quite effective inhibitors of heme oxygenase, but the most powerful inhibitor was found to be zinc‐deuteroporphyrin IX, 2,4‐bisglycol. This metalloporphyrin almost completely inhibits liver heme oxygenase at concentrations as low as 0.5 μ M . Its potency as an inhibitor was found to be greater than that of tin‐protoporphyrin; the K i of zinc‐deuteroporphyrin IX, 2,4‐bisglycol was calculated to be 0.003 μ M . In conclusion, we demonstrated that zinc‐deuteroporphyrin IX, 2,4‐bisglycol has potent inhibitory effects on human liver, kidney and brain heme oxygenase so that this metalloporphyrin can be considered as an alternative to tin‐protoporphyrin in the treatment of hyperbilirubinemia.