Density functional studies on isomerization of prostaglandin H2 to prostacyclin catalyzed by cytochrome P450.
Reaction mechanisms for the isomerization of prostaglandin H(2) to prostacyclin catalyzed by cytochrome P450 are investigated by the unrestricted Becke's three-parameter plus Lee-Yang-Parr density functional level of theory. The results show that the homolytic O-O bond cleavage of endoperoxide in prostaglandin H(2) is the rate-limiting step and that the isomerization proceeds through proton-coupled electron transfer. We located two reaction pathways through an Fe(IV)-porphyrin intermediate and an Fe(III)-porphyrin pi-cation radical intermediate.
Yanai
Tetsuya K
TK
Faculty of Science, Ibaraki University, Bunkyo, Mito 310-8512, Japan.
Mori
Seiji
S
D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004579:Electron Transport; D011464:Epoprostenol / Q000096:biosynthesis*; D008665:Metalloporphyrins / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D044262:Prostaglandin H2 / Q000378:metabolism*
D008665:Metalloporphyrins; D044262:Prostaglandin H2; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol