CYTOCHROME P450 : A MONOOXYGENASE 365
believed to exist in many oxygenase and peroxidase catalytic cycles, is called
Compound I in many research articles. The O – O heterolytic cleavage reaction
to ( 6 ) is thought be promoted by simultaneous electron transfer from the
porphyrin to the Fe – O bond as the porphyrin π - cation radical is generated.
Two events may happen at this point in the cycle: (1) oxygenation of the sub-
strate or (2) addition of two more electrons and two protons via the oxidase
shunt to produce another molecule of water. The latter step is nonproductive
and the catalytic cycle has then simply completed the reduction of O 2 to two
molecules of water via the reaction:
OH 22 ++→ 442 +−e HO (7.8)
The continuation of the catalytic cycle results in insertion of the ferryl – oxo
oxygen regio - and stereospecifi cally into the camphor C 5 C – H bond ( 7 ), fol-
lowed by release of the 5 - exo - hydroxylated camphor and re - generation of the
initial member of the cycle.
7.4.3 Cytochrome P450: Mechanism of Activity,
As will be discussed further in Section 7.4.5 , intermediates ( 5a ), ( 5b ), and ( 6 )
(Figure 7.14 ) are too reactive to build up during catalytic turnover. This has
led to the assumption that intermediate ( 6 ), or compound I, is the “ active
oxygen ” species responsible for alkane hydroxylation, alkene epoxidations,
Figure 7.14 P450CAM catalytic cycle. [Adapted with permission from Figure 2 of
reference 34 (copyright 2005, American Chemical Society) and Figure 1 of reference
35 (copyright 2000, AAAS).]
FeIIIH 2 OSFeII
SOO-FeIIISOO2-FeIII
SOOH-FeIIIe-
H+H+SO
FeIVSROH
FeIII FeIII
SRH
e-RH (camphor substrate)RHO 2SH 2 ORH RH RHRHROHH 2 OH+H 2 O 2O 2 −(1)(2)
PDB: 1DZ4
(2CPP)(3) PDB: 1DZ6
(# 5 in reference 35)(4) PDB: 1DZ8
(# 6 in reference 35)
See Figure 7.13(5a)(5b)(6) PDB: 1DZ9
(# 7 in reference 35)
See Figure 7.17
"Compound I"
activated oxygen
(7)2e-, 2H+oxidase shuntperoxide shunt auto-oxidationshunt