Camphor cytochrome P450 hydroxylation

Zurek, J., Foloppe, N., Harvey, J.N., Mulholland, A.J. Mechanisms of reaction in cytochrome p450 Hydroxylation of camphor in p450CAM. Org. Biomol. Chem. 2006,4(21), 3931-7. 

Some hydroxylation reactions catalyzed by cytochromes P450. Hydroxylation of camphor 1 by P450 g from P. putida [6] Hydroxylation of (S)-/V-methylcoclaurine 3 by CYP80B1 in morphine biosynthesis [7] Hydroxylation of 6-deoxyerythronolide B 5 by P450j from Saccharopolyspora erythraea [8] Hydroxylation of cinnamic acid 7 by CYP73 from Arabidopsis thaliana [9] Hydroxylation of diclofenac 9 by human CYP3A4 [10],... 

Harris D, Loew G. Prediction of regiospecific hydroxylation of camphor analogs by cytochrome-P450(Cam). J Am Chem Soc 1995 117 2738-2746. 

Schoneboom JC, S Cohen, H Lin, S Shaik, W Thiel (2004) Quantum mechanical/molecular mechanical investigation of the mechanism of C-H hydroxylation of camphor by cytochrome P450(cam) Theory supports a two-state rebound mechanism. J. Am. Chem. Soc. 126 (12) 4017-4034... 

There has been much discussion in the field about the oxygen transfer process 6 —> 7 —> 8. The oxygen rebound mechanism in Scheme 1.1 is consistent with the stereochemical, regiochemical, and allylic scrambling results observed in the oxidation of norbomane, camphor, and cyclohexene by cytochrome P450. The hydroxylation of... 

Gelb, M.H., D.C. Heimbrook, P. Malkonen, and S.G. Sligar (1982). Stereochemistry and deuterium isotope effects in camphor hydroxylation by the cytochrome P450 monoxygenase system. Biochemistry 21, 370-377. 

Alton A, Shaik S, Thiel W (2007) What is the active species of cytochrome p450 during camphor hydroxylation QM/MM studies of different electronic states of compound I and of reduced and oxidized iron-oxo intermediates. J Am Chem Soc 129 8978... 

A different kind of cofactor from PLP is responsible for the chemistry of cytochrome P450 (Fig. 9), an enzyme which oxidizes hydrocarbons. It is known as a mixed-function oxidase, or monooxygenase, because one oxygen atom firom molecular oxygen is incorporated into the product while the other goes on to form water. Cytochrome P450 in the liver, for example, oxidizes and detoxifies many kinds of substances that would otherwise be poisonous. One such well-studied reaction, the hydroxylation of camphor, is depicted below. 

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