Cytochrome c

From New World Encyclopedia


Cytochrome c, somatic
Cytochrome c.png
Cytochrome c with heme
Available structures: 1j3s, 2b4z
Identifiers
Symbol(s) CYCS; HCS; CYC
External IDs OMIM: 123970 MGI: 88578 HomoloGene: 68675
RNA expression pattern

PBB GE CYCS 208905 at tn.png

More reference expression data

Orthologs
Human Mouse
Entrez 54205 13063
Ensembl ENSG00000172115 n/a
Uniprot P99999 n/a
Refseq NM_018947 (mRNA)
NP_061820 (protein)
XM_975140 (mRNA)
XP_980234 (protein)
Location Chr 7: 25.12 - 25.13 Mb n/a
Pubmed search [1] [2]

Cytochrome c, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It is a soluble protein, unlike other cytochromes, and serves an important role in energy transfer within cells, being an essential component of the electron transfer chain, where it carries one electron. Cytochrome c is capable of repetitively undergoing either oxidation or reduction, but it does not bind oxygen.

Cytochrome c is a small protein of about 100 amino acids. As such, it has been amenable to determination of its amino acid sequences, and such sequences have been elucidated for many organisms, from yeast to humans.

Overall, cytochrome c reflects on the unity of nature, as it is universally found in aerobic organisms, and with a great deal of similarity among diverse organisms, suggesting a common ancestor that used this protein, and long before basic divergences between plants and animals. Likewise, studies of the small variations in the amino acid sequence of cytochrome c among diverse eukaryotes provides support for the view of a step-wise progression or evolutionary descent with modification, with the more similar sequences found in organisms that appear more related (monkeys and cattle) than between those that seem less related (monkeys and fish). The cytochrome c of chimpanzees is identical to that of humans, but very different from that of bread mold.

Overview

Cytochromes are, in general, membrane-bound hemoproteins that contain heme groups and carry out electron transport. A heme (American English) or haem (British English) is a prosthetic group (the non-protein component of an otherwise protein molecular complex) comprising an iron atom residing in the center of a large heterocyclic organic molecule called a porphyrin. $$$A porphyrin with a metal atom—often, but not always, iron—at the center acts as the prosthetic group in a variety of complex molecules whose general name is metalloproteinsIn living systems there a many different Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic subunit; these are known as hemoproteins. Although$$$

Cytochromes are found either as monomeric proteins (e.g., cytochrome c) or as subunits of bigger enzymatic complexes that catalyze redox reactions. They are found in the mitochondrial inner membrane and endoplasmic reticulum of eukaryotes, in the chloroplasts of plants, in photosynthetic microorganisms, and in bacteria.

The heme group is a highly-conjugated ring system (which means its electrons are very mobile) surrounding a metal ion, which readily interconverts between the oxidation states. The metal ion of iron interconverts between Fe2+ (reduced) and Fe3+ (oxidized) states (electron-transfer processes) or between Fe2+ (reduced) and Fe3+ (formal, oxidized) states (oxidative processes). Cytochromes are, thus, capable of performing oxidation and reduction. Because the cytochromes (as well as other complexes) are held within membranes in an organized way, the redox reactions are carried out in the proper sequence for maximum efficiency.

In the process of oxidative phosphorylation, which is the principal energy-generating process undertaken by organisms that need oxygen to survive, other membrane-bound and -soluble complexes and cofactors are involved in the chain of redox reactions, with the additional net effect that protons (H+) are transported across the mitochondrial inner membrane. The resulting transmembrane proton gradient (protonmotive force) is used to generate ATP, which is the universal chemical energy currency of life. ATP is consumed to drive cellular processes that require energy (such as synthesis of macromolecules, active transport of molecules across the membrane, and assembly of flagella).

Several kinds of cytochromes exist and can be distinguished by spectroscopy, exact structure of the heme group, inhibitor sensitivity, and reduction potential. Three basic types are distinguished by their prosthetic groups: cytochrome a, cytochrome b, and cytochrome d. Cytochrome c is the fourth type of cytochrome, but is not defined in terms of the heme group. In mitochondria and chloroplasts, these cytochromes are often combined in electron transport and related metabolic pathways.

Description

Cytochromes c (cytC) are electron-transfer proteins having one or several heme c groups, bound to the protein by one or, more generally, two thioether bonds involving sulphydryl groups of cysteine residues. The fifth heme iron ligand is always provided by a histidine residue. Cytochromes c possess a wide range of properties and function in a large number of different redox processes (Pettigrew and Moore 1987).

Cytochrome c's primary structure consists of a chain of 100 amino acids. It transfers electrons between Complexes III and IV.

R. P. Ambler (1991) recognized four classes of cytochrome c:

  • Class I includes the low­spin soluble cytochrome c of mitochondria and bacteria. It has the heme-­attachment site towards the N­ terminus of histidine and the sixth ligand provided by a methionine residue towards the C ­terminus.
  • Class II includes the high­spin cytochrome c'. It has the heme-m­attachment site closed to the N terminus of histidine.
  • Class III comprises the low redox potential multiple­ heme cytochromes. The heme c groups are structurally and functionally nonequivalent and present different redox potentials in the range 0 to -400 mV.
  • Class IV was originally created to hold the complex proteins that have other prosthetic groups as well as heme c.

Functions

File:ETC.PNG
Electron Transport Chain
File:Etc2.png
Mitochondrial Electron Transport Chain

Cytochrome c can catalyze several reactions such as hydroxylation and aromatic oxidation, and shows peroxidase activity by oxidation of various electron donors such as 2,2-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), 2-keto-4-thiomethyl butyric acid and 4-aminoantipyrine.

Role in low level laser therapy

Cytochrome c is also suspected to be the functional complex in so called LLLT: Low-level laser therapy. In LLLT, laser light on the wavelength of 670 nanometers penetrates wounded and scarred tissue in order to increase cellular regeneration. Light of this wavelength appears capable of increasing activity of cytochrome c, thus increasing metabolic activity and freeing up more energy for the cells to repair the tissue.

Role in apoptosis

Cytochrome c is also an intermediate in apoptosis, a controlled form of cell death used to kill cells in the process of development or in response to infection or DNA damage (Liu et al. 1996).

Cytochrome c is released by the mitochondria in response to pro-apoptotic stimuli. The sustained elevation in calcium levels precedes cyt c release from the mitochondria. The release of small amounts of cyt c leads to an interaction with the IP3 receptor (IP3R) on the endoplasmic reticulum (ER), causing ER calcium release. The overall increase in calcium triggers a massive release of cyt c, which then acts in the positive feedback loop to maintain ER calcium release through the IP3Rs. This explains how the ER calcium release can reach cytotoxic levels. This release in turn activates caspase 9, a cysteine protease. Caspase 9 can then go on to activate caspases 3 and 7, which are responsible for destroying the cell from within.

Variation

File:Cytochrome C.PNG
Cytochrome c, heme shown in red.

Cytochrome c is a highly conserved protein across the spectrum of species, found in plants, animals, and many unicellular organisms. This, along with its small size (molecular weight about 12,000 daltons), makes it useful in studies of evolutionary relatedness via cladistics.

The cytochrome c molecule of diverse organisms has been studied for the glimpse it gives into evolutionary biology. Both chickens and turkeys have the identical molecule (amino acid for amino acid) within their mitochondria, whereas ducks possess molecules differing by one amino acid. Similarly, both humans and chimpanzees have the identical molecule, while rhesus monkeys possess cytochromes differing by one amino acid.

References
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Further reading


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