View source for Cytochrome P450

{{Pfam box
| Symbol = p450
| Name = 
| image =CytP450Oxidase-1OG2.png
| width = 
| caption = Cytochrome P450 Oxidase (CYP2C9)
| Pfam= PF00067
| InterPro= IPR001128
| SMART=
| PROSITE= PDOC00081
| SCOP = 2cpp
| TCDB =
| OPM family= 41
| OPM protein= 1w0f
| PDB = (More than 171 PDB structures deposited)
}}
{{SI}}
{{CMG}}


==Overview==
'''Cytochrome P450''' (abbreviated '''CYP''', '''P450''', infrequently '''CYP450''') is a very large and diverse superfamily of [[hemoprotein]]s found in all [[domain]]s of life.<ref>{{GoldBookRef|title=cytochrome P450|file=CT06821}} {{cite journal |author=Danielson P |title=The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans |journal=Curr Drug Metab |volume=3 |issue=6 |pages=561–97 |year=2002 |pmid=12369887 |doi=10.2174/1389200023337054}}</ref>  Cytochromes P450 use a plethora of both exogenous and endogenous compounds as substrates in enzymatic reactions. Usually they form part of multicomponent electron transfer chains, called [[P450-containing systems]].

The most common reaction catalysed by cytochrome P450 is a [[monooxygenase]] reaction, e.g. insertion of one atom of oxygen into an organic substrate (RH) while the other oxygen atom is reduced to water:
<center>
RH + O<sub>2</sub> + 2H<sup>+</sup> + 2e<sup>&ndash;</sup> → ROH + H<sub>2</sub>O
</center>
CYP [[enzyme]]s have been identified from all lineages of life, including [[mammal]]s, birds, [[fish]], [[insect]]s, [[worm]]s, sea squirts, sea urchins, [[plant]]s, [[fungus|fungi]], [[slime mold]]s, [[bacteria]] and [[archaea]]. More than '''7700''' distinct CYP sequences are known (as of September 2007; see the web site of the P450 Nomenclature Committee for current counts).<ref name="Dr-Nelson">{{cite web|
|url=http://drnelson.utmem.edu/CytochromeP450|title=Dr. Nelson Lab Website |accessdate=2007-11-19}}</ref>

The name '''cytochrome P450''' is derived from the fact that these are colored ('chrome') cellular ('cyto') proteins, with a "pigment at 450 nm", so named for the characteristic [[Soret peak]] formed by absorbance of light at wavelengths near 450 nm when the heme iron is reduced (often with [[sodium dithionite]]) and complexed to [[carbon monoxide]]. 

==Nomenclature==
[[Genes]] encoding CYP enzymes, and the enzymes themselves, are designated with the abbreviation "CYP", followed by an Arabic numeral indicating the gene family, a capital letter indicating the subfamily, and another numeral for the individual gene. The convention is to italicise the name when referring to the gene. For example, ''CYP2E1'' is the gene that encodes the enzyme [[CYP2E1]] – one of the enzymes involved in [[paracetamol]] (acetaminophen) metabolism. The "CYP" nomenclature is the officially preferred naming convention. However, some gene or enzyme names for CYPs may differ from this nomenclature, denoting the catalytic activity and the name of the compound used as substrate. Examples include CYP5A1, [[thromboxane]] A<sub>2</sub> synthase, abbreviated to TBXAS1 ('''T'''hrom'''B'''o'''X'''ane '''A'''<sub>2</sub> '''S'''ynthase '''1'''), and CYP51, lanosterol 14-α-demethylase, sometimes unofficially abbreviated to LDM according to its substrate ('''L'''anosterol) and activity ('''D'''e'''M'''ethylation). <ref>{{Cite web|url=http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=protein&id=73975753
|title=NCBI sequence viewer|accessdate=2007-11-19}}</ref>

The current nomenclature guidelines suggest that members of new CYP families share >40% amino acid identity, while members of subfamiles must share >55% amino acid identity. There is a [http://drnelson.utmem.edu/CytochromeP450.html Nomenclature Committee] that keeps track of and assigns new names.

==Mechanism==
{{Main|P450-containing systems}}
[[Image:P450cycle.svg|The P450 catalytic cycle|left|thumb|300px]]
The active site of cytochrome P450 contains a [[heme]] iron center. The iron is tethered to the P450 protein via a [[thiolate]] ligand derived from a [[cysteine]] residue. This cysteine and several flanking residues are highly conserved in known CYPs and have the formal [[PROSITE]] signature consensus pattern [FW] - [SGNH] - x - [GD] - {F} - [RKHPT] - {P} - <u>C</u> - [LIVMFAP] - [GAD].<ref>[http://www.expasy.org/cgi-bin/nicedoc.pl?PDOC00081 [[PROSITE]] consensus pattern for P450]</ref> Because of the vast variety of reactions catalyzed by CYPs, the activities and properties of the many CYPs differ in many aspects. In general, the P450 catalytic cycle proceeds as follows:

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,
often displacing a water molecule from the distal axial coordination position of the
heme iron<ref name=P450Mechanism>
{{cite journal
  | author = Bernard Meunier, Samuël P. de Visser and Sason Shaik
  | title = Mechanism of Oxidation Reactions Catalyzed by Cytochrome P450 Enzymes
  | journal = Chemical Reviews
  | volume = 104
  | issue = 9
  | pages = 3947–3980
  | date = 2004
  | doi = 10.1021/cr020443g }}</ref>, and sometimes changing the state of the heme iron from
low-spin to high-spin<ref name=HiResCam>
{{cite journal
  | author =Thomas L. Poulos, Barry C. Finzel and Andrew J. Howard
  | title =High-resolution crystal structure of cytochrome P450<sub>cam</sub>
  | journal =Journal of Molecular Biology
  | volume =195
  | issue =3
  | pages =687–700
  | date = 1987
  | doi =10.1016/0022-2836(87)90190-2 }}
</ref>.  This gives rise to a change in the
spectral properties of the enzyme, with an increase in absorbance at 390&nbsp;nm and
a decrease at 420&nbsp;nm. This can be measured by difference spectrometry and is
referred to as the "type&nbsp;I" difference spectrum (see inset graph in
figure).  Some substrates cause an opposite change in
spectral properties, a "reverse type&nbsp;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&nbsp;II difference spectrum, with a maximum at 430&nbsp;nm and
a minimum at 390&nbsp;nm (see inset graph in figure).  If no
reducing equivalents are available, this complex may remain stable, allowing the
degree of binding to be determined from absorbance measurements ''in vitro''<ref name=p450struc>
{{cite book
  | author = P.R. Ortiz de Montellano (Ed.)
  | title = Cytochrome P450 : structure, mechanism, and biochemistry, 2nd ed.
  | publisher = Plenum
  | date = 1995
  | location = New York}}
</ref>

2: The change in the electronic state of the active site favors the transfer
of an electron from NAD(P)H via [[cytochrome P450 reductase]] or another associated [[reductase]]<ref name=P450pot>
{{cite journal
  | author =S. G. Sligar, D. L. Cinti, G. G. Gibson and J. B. Schenkman
  | title =Spin state control of the hepatic cytochrome P450 redox potential
  | journal =Biochemical and Biophysical Research Communications
  | volume =90
  | issue =3
  | pages =925–932
  | date =1979
  | doi =10.1016/0006-291X(79)91916-8}}
</ref>. This takes place by way of 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<ref name=P450Mechanism />.

4: A second electron is transferred via the electron-transport system, either from [[cytochrome P450 reductase]], [[ferredoxin]]s, or [[cytochrome b5]], 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 water or from surrounding amino-acid side chains, releasing one water molecule,
and forming a highly reactive iron(V)-oxo species<ref name=P450Mechanism />.

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<ref name=p450struc />.  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.

Because most CYPs require a protein partner to deliver one or more electrons to reduce the iron (and eventually molecular oxygen), CYPs are properly speaking part of [[P450-containing systems]] of proteins. Five general schemes are known:
*'''CPR/cyb5/P450 systems''' employed by most [[eukaryotic]] [[microsome|microsomal]] (i.e., not [[mitochondrial]]) CYPs involve the reduction of [[cytochrome P450 reductase]] (variously CPR,POR, or CYPOR) by [[NADPH]], and the transfer of reducing power as electrons to the CYP. [[Cytochrome b5]] (cyb5) can also contribute reducing power to this system after being reduced by [[cytochrome b5 reductase]] (CYB5R).
*'''FR/Fd/P450 systems''' which are employed by [[mitochondrial]] and some [[bacterial]] CYPs.
*'''CYB5R/cyb5/P450 systems''' in which both electrons required by the CYP come from [[cytochrome b5]].
*'''FMN/Fd/P450 systems''' originally found in ''Rhodococcus'' sp. in which a [[FMN]]-domain-containing reductase is fused to the CYP.
*'''P450 only''' systems, which do not require external reducing power. Notably these include [[thromboxane synthase|CYP5]] ([[thromboxane synthase]]), [[prostacyclin synthase|CYP8]], [[prostacyclin synthase]], and CYP74A (allene oxide synthase).

==P450s in humans==
Human CYPs are primarily membrane-associated [[protein]]s, located either in the inner membrane of [[mitochondria]] or in the [[endoplasmic reticulum]] of cells. CYPs metabolize thousands of endogenous and exogenous compounds. Most CYPs can metabolize multiple substrates, and many can catalyze multiple reactions, which accounts for their central importance in metabolizing the extremely large number of endogenous and exogenous molecules.  In the [[liver]], these substrates include drugs and toxic compounds as well as metabolic products such as [[bilirubin]] (a breakdown product of hemoglobin). Cytochrome P450 enzymes are present in most other tissues of the body, and play important roles in [[hormone]] synthesis and breakdown (including [[estrogen]] and [[testosterone]] synthesis and metabolism), [[cholesterol]] synthesis, and [[vitamin D]] metabolism. [[Hepatic]] cytochromes P450 are the most widely studied.

The [[Human Genome Project]] has identified 57 human [[gene]]s coding for the various cytochrome P450 enzymes.<ref name="P450table">{{Cite web|title="P450 Table"
|url=http://drnelson.utmem.edu/human.P450.table.html}}</ref>

===Medications inhibiting CYPs===
Several classes of antifungal medications, including [[imidazole]] and [[triazole]]-class drugs, function via the inhibition of the CYP450 enzyme [[14α-demethylase]]. 

===Drug metabolism===
CYPs are the major enzymes involved in drug metabolism, accounting for ∼75% of the total metabolism.<ref>{{cite journal |author= F. Peter Guengerich |title=Cytochrome P450 and Chemical Toxicology |journal=Chemical Research in Toxicology |volume=21 |pages=70–83 |year=2008 |doi= 10.1021/tx700079z}}</ref>. Cytochrome P450 is the most important element of oxidative metabolism (also known as [[Drug metabolism#Phase I vs. Phase II|phase I metabolism]]). (Metabolism in this context is the chemical modification or degradation of drugs.) 

====Drug interaction====
Many drugs may increase or decrease the activity of various CYP isozymes in a phenomenon known as [[enzyme induction and inhibition]]. This is a major source of adverse [[drug interaction]]s, since changes in CYP enzyme activity may affect the [[drug metabolism|metabolism]] and [[medical clearance|clearance]] of various drugs. For example, if one drug inhibits the CYP-mediated metabolism of another drug, the second drug may accumulate within the body to toxic levels, possibly causing an [[overdose]]. Hence, these drug interactions may necessitate dosage adjustments or choosing drugs which do not interact with the CYP system. Such drug interactions are especially important to take into account when using drugs of vital importance to the patient, drugs with important [[side effects]] and drugs with small [[therapeutic window]]s, but any drug may be subject to an altered plasma concentration due to altered [[drug metabolism]].

A classical example includes [[Anticonvulsant|anti-epileptic drugs]]. [[Phenytoin]], for example, induces [[CYP1A2]], [[CYP2C9]], [[CYP2C19]] and [[CYP3A4]]. Substrates for the latter may be drugs with critical dosage, like [[amiodarone]] or [[carbamazepine]], whose [[blood plasma]] [[concentration]] may decrease because of enzyme induction.

====Interaction of other substances====
In addition, naturally occurring compounds may cause a similar effect. For example, [[bioactive]] compounds found in [[grapefruit juice]] and some other fruit juices, including [[bergamottin]], [[dihydroxybergamottin]], and paradisin-A, have been found to inhibit CYP3A4-mediated metabolism of [[List of drugs affected by grapefruit|certain medications]], leading to increased [[bioavailability]] and thus the strong possibility of [[overdosing]].<ref>{{cite journal |author=Bailey DG, Dresser GK |title=Interactions between grapefruit juice and cardiovascular drugs |journal=Am J Cardiovasc Drug |volume=4 |issue=5 |pages=281–297 |year=2004 |pmid=15449971 |doi=10.2165/00129784-200404050-00002}}</ref> Because of this risk, avoiding grapefruit juice and fresh grapefruits entirely while on drugs is usually advised.<ref>{{cite web |url=http://www.mayoclinic.com/health/food-and-nutrition/AN00413|title=Mayo Clinic |accessdate= 17 December 2008}}</ref>

Other examples:
*[[Saint-John's wort]], a common [[herbal remedy]] induces [[CYP3A4]].
*[[Tobacco smoking]] induces [[CYP1A2]] (example CYP1A2 substrates are [[clozapine]],[[olanzapine]], and [[fluvoxamine]])<ref>{{cite journal | title=Drug interactions with smoking.| author=Kroon LA |journal=Am J Health Syst Pharm |year=2007 | volume=64| issue=18 |page=1917-1921|pmid= 17823102 }}</ref>

===Other specific CYP functions===
[[Image:Steroidogenesis.svg|thumb|left|250px|[[Steroidogenesis]], showing many of the enzyme activities that are performed by cytochrome P450 enzymes. HSD: Hydroxysteroid dehydrogenase]]
A subset of cytochrome P450 enzymes play important roles in the synthesis of [[steroid hormone]]s ([[steroidogenesis]]) by the [[adrenal gland|adrenal]]s, [[gonad]]s, and peripheral tissue: 
*[[CYP11A1]] (also known as P450scc or P450c11a1) in adrenal [[mitochondrion|mitochondria]] effects “the activity formerly known as 20,22-desmolase” (steroid 20α-hydroxylase, steroid 22-hydroxylase, cholesterol [[side chain]] scission).
*[[CYP11B1]] (encoding the protein P450c11β) found in the [[inner mitochondrial membrane]] of [[adrenal cortex]] has steroid 11β-hydroxylase, steroid [[18-hydroxylase]], and steroid 18-methyloxidase activities.
*[[CYP11B2]] (encoding the protein P450c11AS), found only in the mitochondria of the adrenal [[zona glomerulosa]], has steroid 11β-hydroxylase, steroid 18-hydroxylase, and steroid 18-methyloxidase activities.
*[[CYP17A1]], in endoplasmic reticulum of adrenal cortex has steroid 17α-hydroxylase and 17,20-lyase activities.
*[[CYP21A1]] (P450c21) in adrenal cortex conducts [[21-hydroxylase]] activity.
*[[CYP19A]] (P450arom, [[aromatase]]) in [[endoplasmic reticulum]] of [[gonads]], [[brain]], [[adipose tissue]], and elsewhere catalyzes aromatization of [[androgens]] to [[estrogens]].

===CYP Families in Humans===
Humans have 57 genes and more than 59 [[pseudogenes]] divided among 18 families of cytochrome P450 genes and 43 subfamilies.<ref>Nelson D (2003). [http://drnelson.utmem.edu/P450lect.html Cytochrome P450s in humans]. Retrieved May 9, 2005.</ref> This is a summary of the genes and of the proteins they encode. See the homepage of the Cytochrome P450 Nomenclature Committee for detailed information.<ref name="P450table" />

{| class="wikitable"
| '''Family''' || '''Function''' || '''Members''' || '''Names'''
 |- 
 | '''CYP1''' ||  drug and steroid (especially [[estrogen]]) metabolism   || 3 subfamilies, 3 genes, 1 [[pseudogene]]  ||  [[CYP1A1]], [[CYP1A2]], [[CYP1B1]] 
 |- 
 | '''CYP2''' ||  drug and [[steroid]] metabolism   || 13 subfamilies, 16 genes, 16 [[pseudogene]]s  ||  [[CYP2A6]], [[CYP2A7]], [[CYP2A13]], [[CYP2B6]], [[CYP2C8]], [[CYP2C9]], [[CYP2C18]], [[CYP2C19]], [[CYP2D6]], [[CYP2E1]], [[CYP2F1]], [[CYP2J2]], [[CYP2R1]], [[CYP2S1]], [[CYP2U1]], [[CYP2W1]]
 |- 
 | '''CYP3''' ||  drug and [[steroid]] (including [[testosterone]]) metabolism   || 1 subfamily, 4 genes, 2 [[pseudogene]]s  ||  [[CYP3A4]], [[CYP3A5]], [[CYP3A7]], [[CYP3A43]]
 |- 
 | '''CYP4''' ||  [[arachidonic acid]] or fatty acid metabolism   || 6 subfamilies, 11 genes, 10  [[pseudogene]]s  ||  [[CYP4A11]], [[CYP4A22]], [[CYP4B1]], [[CYP4F2]], [[CYP4F3]], [[CYP4F8]], [[CYP4F11]], [[CYP4F12]], [[CYP4F22]], [[CYP4V2]], [[CYP4X1]], [[CYP4Z1]]
 |- 
 | '''CYP5''' ||  [[thromboxane]] A<sub>2</sub> [[thromboxane-A synthase|synthase]]   || 1 subfamily, 1 gene  ||  [[Thromboxane-A synthase|CYP5A1]]
 |- 
 | '''CYP7''' ||  [[bile acid]] biosynthesis 7-alpha hydroxylase of steroid nucleus   || 2 subfamilies, 2 genes  ||  [[CYP7A1]], [[CYP7B1]]
 |- 
 | '''CYP8'''  || ''varied''  || 2 subfamilies, 2 genes  ||  [[CYP8A1]] ([[prostacyclin]] synthase), [[CYP8B1]] (bile acid biosynthesis)
 |- 
 | '''CYP11''' ||  [[steroid]] biosynthesis   || 2 subfamilies, 3 genes  ||  [[CYP11A1]], [[CYP11B1]], [[CYP11B2]]
 |- 
 | '''CYP17''' ||  [[steroid]] biosynthesis, 17-alpha hydroxylase  || 1 subfamily, 1 gene   ||  [[CYP17A1]]
 |- 
 | '''CYP19''' ||  [[steroid]] biosynthesis: [[aromatase]] synthesizes [[estrogen]]    || 1 subfamily, 1 gene  ||  [[CYP19A1]]
 |- 
 | '''CYP20''' ||  unknown function   || 1 subfamily, 1 gene  ||  [[CYP20A1]]
 |- 
 | '''CYP21''' ||  [[steroid]] biosynthesis   || 2 subfamilies, 2 genes, 1 pseudogene  ||  [[CYP21A2]]
 |- 
 | '''CYP24''' ||  [[vitamin D]] degradation   || 1 subfamily, 1 gene  ||  [[CYP24A1]]
 |- 
 | '''CYP26''' ||  [[retinoic acid]] hydroxylase   || 3 subfamilies, 3 genes  ||  [[CYP26A1]], [[CYP26B1]], [[CYP26C1]]
 |- 
 | '''CYP27''' || ''varied''  || 3 subfamilies, 3 genes  ||  [[CYP27A1]] ([[bile acid]] biosynthesis), [[CYP27B1]] (vitamin D3 1-alpha hydroxylase, activates vitamin D3), [[CYP27C1]] (unknown function)
 |- 
 | '''CYP39''' ||  7-alpha hydroxylation of 24-hydroxycholesterol   || 1 subfamily, 1 gene  ||  [[CYP39A1]]
 |- 
 | '''CYP46''' ||  [[cholesterol]] 24-hydroxylase   || 1 subfamily, 1 gene  ||  [[CYP46A1]]
 |- 
 | '''CYP51''' ||  [[cholesterol]] biosynthesis   || 1 subfamily, 1 gene, 3 pseudogenes  ||  [[CYP51A1]] ([[lanosterol]] 14-alpha demethylase)
|}

==P450s in animals==

Many animals have as many or more CYP genes than humans do. For example, mice have genes for 101 CYPs, and sea urchins have even more (perhaps as many as 120 genes).<ref>
{{cite journal
  | last = Goldstone
  | first = Jared
  | coauthors = ''et al.''
  | title = The chemical defensome: environmental sensing and response genes in the ''Strongylocentrotus purpuratus'' genome
  | journal = Dev Biol
  | volume = 300
  | issue = 1
  | pages = 366–384
  | date = 2006
  | doi = 10.1016/j.ydbio.2006.08.066}}
</ref>
Most CYP enzymes are presumed to have monooxygenase activity, as is the case for most mammalian CYPs that have been investigated (except for e.g. [[aromatase|CYP19]] and [[Thromboxane-A synthase|CYP5]]). However, [[gene]] and [[genome sequencing]] is far outpacing [[biochemical]] characterization of enzymatic function, although many genes with close [[homology]] to CYPs with known function have been found.

The classes of CYPs most often investigated in non-human animals are those involved in either [[developmental biology|development]] (e.g. [[retinoic acid]] or [[hormone]] metabolism) or involved in the metabolism of toxic compounds (such as heterocyclic amines or [[polyaromatic hydrocarbons]]). Often there are differences in [[gene regulation]] or enzyme function of CYPs in related animals that explain observed differences in susceptibility to toxic compounds.

CYPs have been extensively examined in mice, rats, and dogs, and less so in [[zebrafish]], in order to facilitate use of these [[model organisms]] in [[drug discovery]] and [[toxicology]]. 

CYPs have also been heavily studied in [[insects]], often to understand [[pesticide resistance]].

==P450s in bacteria==

Bacterial cytochromes P450 are often soluble enzymes and are involved in critical metabolic processes. Three examples that have contributed significantly to structural and mechanistic studies are listed here, but many different families exist.

* Cytochrome P450cam (CYP101) originally from ''[[Pseudomonas putida]]'' has been used as a model for many cytochrome P450s and was the first cytochrome P450 three-dimensional protein structure solved by x-ray crystallography.  This enzyme is part of a camphor-hydroxylating catalytic cycle consisting of two electron transfer steps from putidaredoxin, a 2Fe-2S cluster-containing protein cofactor.

* Cytochrome P450 eryF (CYP107A1) originally from the actinomycete bacterium ''Saccharopolyspora erythraea'' is responsible for the biosynthesis of the [[antibiotic]] [[erythromycin]] by C6-hydroxylation of the macrolide 6-deoxyerythronolide B.

* Cytochrome P450 BM3 (CYP102A1) from the soil bacterium ''[[Bacillus megaterium]]'' catalyzes the  NADPH-dependent hydroxylation of several [[long-chain fatty acid]]s at the ω–1 through ω–3 positions. Unlike almost every other known CYP (except CYP505A1, cytochrome P450 foxy), it constitutes a natural fusion protein between the CYP domain and an electron donating cofactor. Thus, BM3 is potentially very useful in biotechnological applications.<ref>{{cite journal |author=Narhi L, Fulco A |title=Characterization of a catalytically self-sufficient 119,000-dalton cytochrome P-450 monooxygenase induced by barbiturates in ''Bacillus megaterium'' |journal=J Biol Chem |volume=261 |issue=16 |pages=7160–9 |year=1986 |pmid=3086309 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=3086309 |date=06/05/1986 }}</ref><ref>{{cite journal |author=Girvan H, Waltham T, Neeli R, Collins H, McLean K, Scrutton N, Leys D, Munro A |title=Flavocytochrome P450 BM3 and the origin of CYP102 fusion species |journal=Biochem Soc Trans |volume=34 |issue=Pt 6 |pages=1173–7 |year=2006 |pmid=17073779 |doi=10.1042/BST0341173}}</ref>

==P450s in fungi==

The commonly used azole antifungal agents work by inhibition of the fungal [[cytochrome P450 14α-demethylase]]. This interrupts the conversion of lanosterol to [[ergosterol]], a component of the fungal cell membrane.

==P450s in plants==

Plant cytochrome P450s are involved in a wide range of biosynthetic reactions, leading to various [[fatty acid]] conjugates, plant hormones, defensive compounds, or medically important drugs. [[Terpenoid]]s, which represent the largest class of characterized natural plant compounds, are often substrates for plant CYPs.

==InterPro subfamilies==
[[InterPro]] subfamilies:
*Cytochrome P450, B-class {{InterPro|IPR002397}}
*Cytochrome P450, mitochondrial {{InterPro|IPR002399}}
*Cytochrome P450, E-class, group I {{InterPro|IPR002401}}
*Cytochrome P450, E-class, group II {{InterPro|IPR002402}}
*Cytochrome P450, E-class, group IV {{InterPro|IPR002403}}

==References==
{{reflist|2}}

==External links==
*[http://www.cypalleles.ki.se/ Human Cytochrome P450 (CYP) Allele Nomenclature Committee] at Karolinska Institutet
*[http://drnelson.utmem.edu/CytochromeP450.html Cytochrome P450 Homepage] – David Nelson's P450 database at University of Tennessee Health Science Center
*[http://medicine.iupui.edu/flockhart/ Cytochrome P450 drug interaction table] – popular source for P450-mediated drug interaction information at Indiana University-Purdue University Indianapolis
*[http://www.icgeb.org/~p450srv/ Kiril's Directory of P450 resources] at [[International Centre for Genetic Engineering and Biotechnology]]
*[http://p450.antibes.inra.fr/ The Insect P450 Site] (run by Rene Feyereisen) at Institut National de la Recherche Agronomique
* {{UMichOPM|families|superfamily|41}}
* {{cite journal |author=Estabrook R |title=A passion for P450s (rememberances of the early history of research on cytochrome P450) |journal=Drug Metab Dispos |volume=31 |issue=12 |pages=1461–73 |year=2003 |pmid=14625342 |url=http://dmd.aspetjournals.org/cgi/content/full/31/12/1461  |doi=10.1124/dmd.31.12.1461}}
*[http://elearn.pharmacy.ac.uk/flash/view/Cytochrome_P450.html Cytochrome P450] Useful teaching tutorial, School of Pharmacy, London - flash animation with audio commentary]
*[http://www.genome.ad.jp/dbget-bin/show_pathway?map00150+1.14.13.- KEGG steroid metabolism pathway]

{{Cytochrome P450}}


[[Category:EC 1.14]]
[[Category:Cytochrome P450]]
[[Category:Pharmacokinetics]]
[[Category:Metabolism]]
[[Category:Integral membrane proteins]]
[[Category:Enzymes]]

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