Functional differences between peroxidase compound I and the cytochrome P-450 reactive oxygen intermediate

Area of Science:

• Biochemistry
• Enzymology
• Oxidative Metabolism

Background:

• Hemeproteins are crucial catalysts in biological oxidation reactions.
• Cytochrome P-450 enzymes are known for diverse oxidative functions, including hydroxylation and epoxidation.
• Peroxidases also utilize heme prosthetic groups for catalytic activity, but their reaction mechanisms differ.

Purpose of the Study:

• To compare the catalytic activities of various hemeproteins, including cytochromes P-450, peroxidases, and others, across a range of oxidative reactions.
• To identify unique catalytic activities specific to cytochrome P-450 enzymes.
• To investigate the mechanism of peroxide processing by cytochrome P-450 in comparison to peroxidases.

Main Methods:

• Tested seven hemeproteins (cytochromes P-450LM2, P-450LM4, P-420LM2, horseradish peroxidase, chloroperoxidase, catalase, metmyoglobin) and hemin.
• Assessed catalysis of five oxidative reactions: pyrogallol oxidation, aliphatic hydroxylation, aromatic hydroxylation, olefinic epoxidation, and peroxyacid decarboxylation.

Main Results:

• All tested hemeproteins catalyzed peroxidation, with horseradish peroxidase, chloroperoxidase, and catalase being superior catalysts.
• Only cytochrome P-450 enzymes effectively catalyzed hydroxylation and epoxidation reactions.
• Peroxyacid decarboxylation was exclusively observed with cytochrome P-450 enzymes, identifying it as a novel P-450 activity.

Conclusions:

• Cytochrome P-450 enzymes exhibit unique catalytic capabilities, including peroxyacid decarboxylation, distinguishing them from other hemeproteins.
• The distinct decarboxylation activity suggests cytochrome P-450 enzymes process peroxides via homolysis, differing fundamentally from peroxidases.
• These findings question the similarity of reactive oxygen intermediates involved in the oxidative mechanisms of P-450s and peroxidases.