Cytochromes are redox-active
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s containing a
heme
Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
In biochemical terms, heme is a coordination complex "consis ...
, with a central Fe atom at its core, as a
cofactor. They are involved in
electron transport chain and
redox
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...
catalysis
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
. They are classified according to the type of heme and its
mode of binding. Four varieties are recognized by the
International Union of Biochemistry and Molecular Biology
The International Union of Biochemistry and Molecular Biology (IUBMB) is an international non-governmental organisation concerned with biochemistry and molecular biology. Formed in 1955 as the International Union of Biochemistry (IUB), the union ...
(IUBMB), cytochromes a,
cytochromes b,
cytochromes c and
cytochrome d
Cytochrome ''d'', previously known as cytochrome ''a''2, is a name for all cytochromes (electron-transporting heme proteins) that contain heme D as a cofactor. Two unrelated classes of cytochrome ''d'' are known: Cytochrome ''bd'', an enzyme tha ...
.
Cytochrome function is linked to the reversible
redox
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...
change from
ferrous
In chemistry, the adjective Ferrous indicates a compound that contains iron(II), meaning iron in its +2 oxidation state, possibly as the divalent cation Fe2+. It is opposed to " ferric" or iron(III), meaning iron in its +3 oxidation state, suc ...
(Fe(II)) to the
ferric
In chemistry, iron(III) refers to the element iron in its +3 oxidation state. In ionic compounds (salts), such an atom may occur as a separate cation (positive ion) denoted by Fe3+.
The adjective ferric or the prefix ferri- is often used to sp ...
(Fe(III)) oxidation state of the
iron
Iron () is a chemical element with Symbol (chemistry), symbol Fe (from la, Wikt:ferrum, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 element, group 8 of the periodic table. It is, Abundanc ...
found in the heme core. In addition to the classification by the IUBMB into four cytochrome classes, several additional classifications such as
cytochrome o and
cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
can be found in biochemical literature.
History
Cytochromes were initially described in 1884 by
Charles Alexander MacMunn
Dr Charles Alexander MacMunn (11 April 1852 – 18 February 1911) was the first to describe the respiratory pigment in blood, known today as Cytochrome1. It was one of the most significant discoveries made by an Irish doctor.
Biography
MacMunn ...
as respiratory pigments (myohematin or histohematin).
In the 1920s,
Keilin rediscovered these respiratory pigments and named them the cytochromes, or “cellular pigments”. He classified these heme proteins on the basis of the position of their lowest
energy absorption band in their reduced state, as
cytochromes ''a'' (605 nm), ''b'' (≈565 nm), and ''c'' (550 nm). The ultra-violet (UV) to visible spectroscopic signatures of hemes are still used to identify heme type from the reduced bis-pyridine-ligated state, i.e., the pyridine hemochrome method. Within each class, cytochrome ''a'', ''b'', or ''c'', early cytochromes are numbered consecutively, e.g. cyt ''c'', cyt ''c
1'', and cyt ''c
2'', with more recent examples designated by their reduced state R-band maximum, e.g. cyt ''c
559''.
Structure and function
The
heme
Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
In biochemical terms, heme is a coordination complex "consis ...
group is a highly conjugated ring system (which allows its
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 no ...
s to be very mobile) surrounding an iron ion. The iron in cytochromes usually exists in a ferrous (Fe
2+) and a ferric (Fe
3+) state with a ferroxo (Fe
4+) state found in catalytic intermediates.
Cytochromes are, thus, capable of performing
electron transfer reactions and
catalysis
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
by reduction or oxidation of their heme iron. The cellular location of cytochromes depends on their function. They can be found as
globular protein
In biochemistry, globular proteins or spheroproteins are spherical ("globe-like") proteins and are one of the common protein types (the others being fibrous, disordered and membrane proteins). Globular proteins are somewhat water-soluble (formi ...
s and
membrane protein
Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...
s.
In the process of
oxidative phosphorylation, a globular
cytochrome cc protein is involved in the electron transfer from the membrane-bound
complex III
Complex commonly refers to:
* Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe
** Complex system, a system composed of many components which may interact with each ...
to
complex IV
The enzyme cytochrome c oxidase or Complex IV, (was , now reclassified as a translocasEC 7.1.1.9 is a large transmembrane protein complex found in bacteria, archaea, and mitochondria of eukaryotes.
It is the last enzyme in the respiratory electr ...
. Complex III itself is composed of several subunits, one of which is a b-type cytochrome while another one is a c-type cytochrome. Both domains are involved in electron transfer within the complex. Complex IV contains a cytochrome a/a3-domain that transfers electrons and catalyzes the reaction of
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 as ...
to water. Photosystem II, the first
protein complex
A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain.
Protein ...
in the
light-dependent reactions of oxygenic
photosynthesis
Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemical energy is stored i ...
, contains a cytochrome b subunit.
Cyclooxygenase 2
Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (The HUGO official symbol is PTGS2; HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the ''PTGS2'' gene ...
, an enzyme involved in
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
, is a cytochrome b protein.
In the early 1960s, a linear
evolution
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
of cytochromes was suggested by
Emanuel Margoliash
Emanuel Margoliash (February 10, 1920 – April 10, 2008) was a biochemist who spent much of his career studying the protein cytochrome c. He is best known for his work on molecular evolution; with Walter Fitch, he devised Fitch-Margoliash met ...
that led to the
molecular clock
The molecular clock is a figurative term for a technique that uses the mutation rate of biomolecules to deduce the time in prehistory when two or more life forms diverged. The biomolecular data used for such calculations are usually nucleo ...
hypothesis. The apparently constant evolution rate of cytochromes can be a helpful tool in trying to determine when various organisms may have diverged from a
common ancestor
Common descent is a concept in evolutionary biology applicable when one species is the ancestor of two or more species later in time. All living beings are in fact descendants of a unique ancestor commonly referred to as the last universal comm ...
.
Types
Several kinds of cytochrome exist and can be distinguished by
spectroscopy, exact structure of the heme group, inhibitor sensitivity, and reduction potential.
Four types of cytochromes are distinguished by their prosthetic groups:
There is no "cytochrome e," but
cytochrome f
Cytochrome ''f'' is the largest subunit of cytochrome ''b''6''f'' complex (plastoquinol—plastocyanin reductase; ). In its structure and functions, the cytochrome b6f complex bears extensive analogy to the cytochrome bc1 complex of mitochondr ...
, found in the
cytochrome b6f complex of plants is a c-type cytochrome.
In
mitochondria and
chloroplasts, these cytochromes are often combined in
electron transport
An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples thi ...
and related metabolic pathways:
A distinct family of cytochromes is the
cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
family, so named for the characteristic
Soret peak formed by absorbance of light at wavelengths near 450 nm when the heme iron is reduced (with
sodium dithionite
Sodium dithionite (also known as sodium hydrosulfite) is a white crystalline powder with a sulfurous odor. Although it is stable in dry air, it decomposes in hot water and in acid solutions.
Structure
The structure has been examined by Raman s ...
) and complexed to
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 simple ...
. These enzymes are primarily involved in
steroidogenesis
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
and
detoxification
Detoxification or detoxication (detox for short) is the physiological or medicinal removal of toxic substances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of ...
.
References
External links
Scripps Database of Metalloproteins*
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