Cytochromes P450 (CYPs) are a
superfamily
SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilies. Domains are functional, str ...
of
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s containing
heme as a
cofactor that functions as
monooxygenase
Monooxygenases are enzymes that incorporate one hydroxyl group (−OH) into substrates in many metabolic pathways. In this reaction, the two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation o ...
s.
In mammals, these proteins oxidize
steroids,
fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
s, and
xenobiotics, and are important for the
clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963,
Estabrook,
Cooper
Cooper, Cooper's, Coopers and similar may refer to:
* Cooper (profession), a maker of wooden casks and other staved vessels
Arts and entertainment
* Cooper (producers), alias of Dutch producers Klubbheads
* Cooper (video game character), in ...
, and
Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of
defensive compounds, fatty acids, and hormones.
CYP enzymes have been identified in all
kingdoms of life:
animal
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage ...
s,
plant
Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae excl ...
s,
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...
,
protist
A protist () is any eukaryotic organism (that is, an organism whose cells contain a cell nucleus) that is not an animal, plant, or fungus. While it is likely that protists share a common ancestor (the last eukaryotic common ancestor), the e ...
s,
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
, and
archaea, as well as in
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsk ...
es. However, they are not omnipresent; for example, they have not been found in ''
Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
''.
, more than 300,000 distinct CYP proteins are known.
CYPs are, in general, the terminal oxidase enzymes in
electron transfer chains, broadly categorized as
P450-containing systems Any enzyme system that includes cytochrome P450 protein or domain can be called a P450-containing system.
P450 enzymes usually function as a terminal oxidase in multicomponent electron-transfer chains, called P450-containing monooxygenase systems, ...
. The term "P450" is derived from the
spectrophotometric peak at the
wavelength
In physics, the wavelength is the spatial period of a periodic wave—the distance over which the wave's shape repeats.
It is the distance between consecutive corresponding points of the same phase on the wave, such as two adjacent crests, tr ...
of the
absorption maximum
Absorption spectroscopy refers to spectroscopic techniques that measure the absorption of radiation, as a function of frequency or wavelength, due to its interaction with a sample. The sample absorbs energy, i.e., photons, from the radiating ...
of the enzyme (450
nm) when it is in the
reduced state and complexed with
carbon monoxide
Carbon monoxide ( chemical formula CO) is a colorless, poisonous, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the simpl ...
. Most CYPs require a protein partner to deliver one or more
electron
The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family,
and are generally thought to be elementary particles because they have n ...
s to reduce the
iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in ...
(and eventually molecular
oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements ...
).
Nomenclature
Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s encoding CYP enzymes, and the enzymes themselves, are designated with the
root symbol CYP for the
superfamily
SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilies. Domains are functional, str ...
, followed by a number 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
Cytochrome P450 2E1 (abbreviated CYP2E1, ) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, inclu ...
—one of the enzymes involved in
paracetamol (acetaminophen) metabolism. The CYP nomenclature is the official naming convention, although occasionally CYP450 or CYP
450 is used synonymously. 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
2 synthase, abbreviated to
TBXAS1 (ThromBoXane A
2 Synthase 1), and
CYP51A1
Lanosterol 14α-demethylase (CYP51A1) is the animal version of a cytochrome P450 enzyme that is involved in the conversion of lanosterol to 4,4-dimethylcholesta-8(9),14,24-trien-3β-ol. The cytochrome P450 isoenzymes are a conserved group of ...
, lanosterol 14-α-demethylase, sometimes unofficially abbreviated to LDM according to its substrate (Lanosterol) and activity (DeMethylation).
The current nomenclature guidelines suggest that members of new CYP families share at least 40%
amino-acid identity, while members of subfamilies must share at least 55% amino-acid identity. Nomenclature committees assign and track both base gene names
Cytochrome P450 Homepage) and
allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chrom ...
names
CYP Allele Nomenclature Committee.
Classification
Based on the nature of the electron transfer proteins, CYPs can be classified into several groups:
;Microsomal P450 systems: in which electrons are transferred from
NADPH via
cytochrome P450 reductase (variously CPR, POR, or CYPOR).
Cytochrome b5 (cyb
5) can also contribute reducing power to this system after being reduced by
cytochrome b5 reductase (CYB
5R).
;Mitochondrial P450 systems: which employ
adrenodoxin reductase and
adrenodoxin to transfer electrons from NADPH to P450.
;Bacterial P450 systems: which employ a
ferredoxin reductase Ferredoxin reductase may refer to:
* Ferredoxin—NADP(+) reductase (FNR)
* Ferredoxin—NAD(+) reductase
* Ferredoxin—nitrite reductase
* Ferredoxin-thioredoxin reductase
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