Common and Uncommon Cytochrome P450 Reactions Related to Metabolism and Chemical Toxicity

Citations Over TimeTop 1% of 2001 papers

Abstract

Cytochrome P450 (P450) enzymes catalyze a variety of reactions and convert chemicals to potentially reactive products as well as make compounds less toxic. Most of the P450 reactions are oxidations. The majority of these can be rationalized in the context of an FeO(3+) intermediate and odd electron abstraction/rebound mechanisms; however, other iron-oxygen complexes are possible and alternate chemistries can be considered. Another issue regarding P450-catalyzed reactions is the delineation of rate-limiting steps in the catalytic cycle and the contribution to reaction selectivity. In addition to the rather classical oxidations, P450s also catalyze less generally discussed reactions including reduction, desaturation, ester cleavage, ring expansion, ring formation, aldehyde scission, dehydration, ipso attack, one-electron oxidation, coupling reactions, rearrangement of fatty acid and prostaglandin hydroperoxides, and phospholipase activity. Most of these reactions are rationalized in the context of high-valent iron-oxygen intermediates and Fe(2+) reductions, but others are not and may involve acid-base catalysis. Some of these transformations are involved in the bioactivation and detoxication of xenobiotic chemicals.

Related Papers

• → Oxidizing Intermediates in P450 Catalysis: A Case for Multiple Oxidants(2015)33 cited
• → Electrochemical and spectroelectrochemical properties of thiadiazole substituted metallo-phthalocyanines(2015)31 cited
• → One small step for cytochrome P450 in its catalytic cycle, one giant leap for enzymology(2019)5 cited
• → Procedure for the determination of redox potentials of chemically (and electrochemically) irreversible inorganic redox couples from spectroscopic data(1999)10 cited
• → Substituted Hydrocarbons(1972)4 cited