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English: ==The P450 catalytic cycle==

1: The substrate binds to the active site of the enzyme, in close proximity to the heme group, on the side opposite to the peptide chain. The bound substrate induces a change in the conformation of the active site, displacing a water molecule from the distal axial coordination position of the heme iron[1] changing the state of the heme iron from low-spin to high-spin[2]. This gives rise to a change in the spectral properties of the enzyme, with an increase in absorbance at 390~nm and a decrease at 420~nm. This can be measured by difference spectrometry and is referred to as the "type~I" difference spectrum (see inset graph in figure). Some substrates cause an opposite change in spectral properties, a "reverse type~I" spectrum, by processes that are as yet unclear. Inhibitors and certain substrates that bind directly to the heme iron give rise to the type~II difference spectrum, with a maximum at 430~nm and a minimum at 390~nm (see inset graph in figure). If no reducing equivalents are available, this complex remains stable, allowing the degree of binding to be determined from absorbance measurements in vitro[3]

2: The change in the electronic state of the active site favours the transfer of an electron from NAD(P)H[4]. This takes place via the electron transfer chain, as described above, reducing the ferric heme iron to the ferrous state.

3: Molecular oxygen binds covalently to the distal axial coordination position of the heme iron. The cysteine ligand is a better electron donor than histidine, with the oxygen consequently being activated to a greater extent than in other heme proteins. However, this sometimes allows the bond to dissociate, the so-called "decoupling reaction", releasing a reactive superoxide radical, interrupting the catalytic cycle[1].

4: A second electron is transferred via the electron-transport system, reducing the dioxygen adduct to a negatively charged peroxo group. This is a short-lived intermediate state.

5: The peroxo group formed in step 4 is rapidly protonated twice by local transfer from surrounding amino-acid side chains, releasing one mole of water, and forming a highly reactive iron(V)-oxo species[1].

6: Depending on the substrate and enzyme involved, P450 enzymes can catalyse any of a wide variety of reactions. A hypothetical hydroxylation is shown in this illustration. After the product has been released from the active site, the enzyme returns to its original state, with a water molecule returning to occupy the distal coordination position of the iron nucleus. S An alternative route for mono-oxygenation is via the "peroxide shunt": interaction with single-oxygen donors such as peroxides and hypochlorites can lead directly to the formation of the iron-oxo intermediate, allowing the catalytic cycle to be completed without going through steps 3, 4 and 5[3]. A hypothetical peroxide "XOOH" is shown in the diagram.

C: If carbon monoxide (CO) binds to reduced P450, the catalytic cycle is interrupted. This reaction yields the classic CO difference spectrum with a maximum at 450 nm.

  1. a b c Bernard Meunier, Samuël P. de Visser and Sason Shaik (2004). "Mechanism of Oxidation Reactions Catalyzed by Cytochrome P450 Enzymes". Chemical Reviews 104 (9): 3947 - 3980.
  2. Thomas L. Poulos, Barry C. Finzel and Andrew J. Howard (1987). "High-resolution crystal structure of cytochrome P450cam". Journal of Molecular Biology 195 (3): 687-700.
  3. a b P.R. Ortiz de Montellano (Ed.) (1995年) 《 Cytochrome P450 : structure, mechanism, and biochemistry, 2nd ed.》、​Category:New York: Plenum
  4. S. G. Sligar, D. L. Cinti, G. G. Gibson and J. B. Schenkman (1979). "Spin state control of the hepatic cytochrome P450 redox potential". Biochemical and Biophysical Research Communications 90 (3): 925-932.
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来源 M.Sc. Thesis, David Richfield (User:Slashme)
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英语维基百科Slashme When using this image in external works, it may be cited as follows:

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当前2012年4月22日 (日) 15:072012年4月22日 (日) 15:07版本的缩略图9,240 × 6,968(38 KB)Slashme{{Information |Description ={{en|1====The P450 catalytic cycle== 1: The substrate binds to the active site of the enzyme, in close proximity to the heme group, on the side opposite to the peptide chain. The bound substrate induces a change in the ...
2012年4月22日 (日) 14:49没有缩略图9,240 × 6,968(38 KB)SlashmeCorrected peroxide shunt arrow.
2008年7月5日 (六) 10:342008年7月5日 (六) 10:34版本的缩略图9,240 × 6,968(35 KB)Slashme{{Information |Description={{en|1===The P450 catalytic cycle== 1: The substrate binds to the active site of the enzyme, in close proximity to the heme group, on the side opposite to the peptide chain. The bound substrate induces a change in the conforma

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