Cytochrome c
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 an essential component of the electron transfer chain, where it carries one electron. Cytochrome C is capable of undergoing oxidation and reduction, but does not bind oxygen.
Cytochrome C — unity of nature stepwise progression
For example, the protein cytochrome c, which is needed for aerobic respiration, is universally shared in aerobic organisms, suggesting a common ancestor that used this protein.
stepwise There are also variations in the amino acid sequence of cytochrome c, with the more similar molecules found in organisms that appear more related (monkeys and cows) than between those that seem less related (monkeys and fish). The cytochrome c of chimpanzees is the same as that of humans, but very different from 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 that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic subunit; these are known as hemoproteins.
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
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 nanometer 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
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.
ReferencesISBN links support NWE through referral fees
- Ambler, R. P. 1991. Sequence variability in bacterial cytochromes c. Biochim. Biophys. Acta 1058(1): 42-47. Retrieved May 16, 2008.
- Bushnell, G. W., G. V. Louie, and G. D. Brayer. 1990. High-resolution three-dimensional structure of horse heart cytochrome c. J.Mol.Biol. 214: 585-595. Retrieved May 16, 2008.
- Liu, X., C. Kim, J. Yang, R. Jemmerson, and X. Wang. 1996. Induction of apoptotic program in cell-free extracts: Requirement for dATP and cytochrome c. Cell 86(1): 147-57. Retrieved May 16, 2008.
- Pettigrew, G. W. and G. R. Moore. 1987 Cytochromes c: Biological Aspects. New York: SpringerVerlag. ISBN 0387178430.
Further reading
- Broger, C., M. J. Nałecz, and A. Azzi. 1980. Interaction of cytochrome c with cytochrome bc1 complex of the mitochondrial respiratory chain. Biochim. Biophys. Acta 592(3): 519-27. PMID 6251869. Retrieved May 16, 2008.
- Evans, M. J., and R. C. Scarpulla. 1989. The human somatic cytochrome c gene: two classes of processed pseudogenes demarcate a period of rapid molecular evolution. Proc. Natl. Acad. Sci. U.S.A. 85(24): 9625-9. PMID 2849112. Retrieved May 16, 2008.
- Ferri, K. F., E. Jacotot, J. Blanco, et al. 2001. Mitochondrial control of cell death induced by HIV-1-encoded proteins. Ann. N. Y. Acad. Sci. 926: 149-64. PMID 11193032. Retrieved May 16, 2008.
- Garber, E. A., and E. Margoliash. 1990. Interaction of cytochrome c with cytochrome c oxidase: an understanding of the high- to low-affinity transition. Biochim. Biophys. Acta 1015(2): 279-87. PMID 2153405. Retrieved May 16, 2008.
- Haider, N. N. Narula, and J. Narula. 2003. Apoptosis in heart failure represents programmed cell survival, not death, of cardiomyocytes and likelihood of reverse remodeling. J. Card. Fail. 8(6 Suppl): S512-7. PMID 12555167. Retrieved May 16, 2008.
- Lynch, S. R., D. Sherman, and R. A. Copeland. 1992. Cytochrome c binding affects the conformation of cytochrome a in cytochrome c oxidase. J. Biol. Chem. 267(1): 298-302. PMID 1309738. Retrieved May 16, 2008.
- Mannella, C. A. 1998. Conformational changes in the mitochondrial channel protein, VDAC, and their functional implications. J. Struct. Biol. 121(2): 207-18. PMID 9615439. Retrieved May 16, 2008.
- Michel, B., and H. R. Bosshard. 1984. Spectroscopic analysis of the interaction between cytochrome c and cytochrome c oxidase. J. Biol. Chem. 259(16): 10085-91. PMID 6088481. Retrieved May 16, 2008.
- Skulachev, V. P. 1998. Cytochrome c in the apoptotic and antioxidant cascades. FEBS Lett. 423(3): 275-80. PMID 9515723. Retrieved May 16, 2008.
- Tanaka, Y., T. Ashikari, Y. Shibano, et al. 1988. Construction of a human cytochrome c gene and its functional expression in Saccharomyces cerevisiae. J. Biochem. 103(6): 954-61. PMID 2844747. Retrieved May 16, 2008.
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