Thianthrene 5-oxide as a probe of the electrophilicity of hemoprotein oxidizing species
| Autor: | Juan C. Alvarez, Ortiz de Montellano Pr |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Hemeproteins
Male Hemeprotein chemistry.chemical_element Chloride peroxidase Photochemistry Biochemistry Peroxide Medicinal chemistry Horseradish peroxidase Oxygen chemistry.chemical_compound Hemoglobins Nucleophile Cytochrome P-450 Enzyme System Heterocyclic Compounds Oxidizing agent Animals Humans Thianthrene Horseradish Peroxidase biology Molecular Structure Rats Inbred Strains Cyclic S-Oxides Rats Kinetics chemistry Phenobarbital biology.protein Microsomes Liver Chloride Peroxidase Oxidation-Reduction |
| Zdroj: | Biochemistry. 31(35) |
| ISSN: | 0006-2960 |
| Popis: | Thianthrene 5-oxide (T-5-O), which is oxidized to the 5,10- and 5,5-dioxides, respectively, by electrophilic and nucleophilic agents, has been used to determine the electronic properties of hemoprotein oxidizing species. Cytochrome P450 oxidizes T-5-O to the 5,10- rather than the 5,5-dioxide but oxidizes the 5,5-dioxide rapidly and the 5,10-dioxide slowly to the 5,5,10-trioxide. Chloroperoxidase oxidizes T-5-O to the 5,10-dioxide but very poorly oxidizes it further to the 5,5,10-trioxide. It does, however, readily oxidize the 5,5-dioxide to the trioxide. The oxidizing species of cytochrome P450 and chloroperoxidase are thus comparably electrophilic, but the former is more powerful. T-5-O is not detectably oxidized by horseradish peroxidase/H2O2 but is oxidized exclusively to the 5,5-dioxide when the peroxide is replaced by dihydroxyfumaric acid (DHFA). The oxygen incorporated into the 5,5-dioxide in this reaction derives from molecular oxygen. This is consistent with the involvement of a DHFA-derived co-oxidizing species. Oxidation of T-5-O by human hemoglobin and H2O2 yields the 5,5- and 5,10-dioxides and the 5,5,10-trioxide. The oxygen in these products derives primarily (greater than 80%) from H2O2. Hemoglobin and H2O2 thus form both a P450-like electrophilic oxidant (5,10-dioxide) and a peroxide-derived nucleophilic oxidant (5,5-dioxide). A large difference in the cis:trans ratios of the 5,10-dioxides produced from T-5-O by cytochrome P450 (1.3:1) and chloroperoxidase (2.5:1) vs hemoglobin (0.1:1) suggests that the hemoglobin active site severely constrains the geometry of the electrophilic oxidation.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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