Heme c
Encyclopedia
Heme C differs from heme B
in that the two vinyl
side chains of heme B are replaced by covalent, thioether
linkages to the apoprotein
. These linkages do not allow the heme C to easily dissociate from the holoprotein
, cytochrome c
, compared with the more easily dissociated heme B that may dissociate from the holoprotein, the heme-protein complex, even under mild conditions. This allows a very wide range of cytochrome c structure and function, with the myriad of c type cytochromes acting primarily as electron carriers. Cytochromes c, existing as dozens to hundreds of structural and functional subtypes, are found in a wide variety of cell types, even in those organisms living under extreme conditions. While heme B plays a variety of roles in cells, heme C is almost always located in proteins functioning in electron transport reactions most often associated with cell, mitochondria or chloroplast
membranes. Heme C, along with the closely structurally related Heme B, are the most common heme types observed in functioning hemeproteins.
The thioether linkages are commonly arranged with two amino acids between the two cysteinyl groups bound to the heme. This is often written as CXXC, within the amino acid sequence presentation with X being most any common amino acid. Vertebrate c type cytochromes also arrange a histidine
amino acid next to this sequence so that CXXCH represents the five key amino acids associated with the thioether linkages in these proteins. The two thioether bonds are made to heme ring positions 2 and 4, but a few c type cytochromes have hemes with only a single thioether bond.
The number of heme C units bound to a holoprotein is highly variable. For vertebrate cells one heme C per protein is the rule but for bacteria this number is often 2, 4, 5, 6 or even 16 heme C groups per holoprotein. It is generally agreed the number and arrangement of heme C groups are related and even required for proper holoprotein function. For instance, those proteins containing several heme C groups are involved with multiple electron transfer reactions, particularly important is the 6 electron reduction required to reduce atmospheric nitrogen into two organic ammonia molecules. It is common for the heme C to amino acid ratio to be high for bacterial hemeproteins, so the interiors of some cytochrome c proteins appear packed with many heme C groups compared with other hemeproteins. Some hemeproteins, often from single cell organisms, may contain five hemes C. The bc1 complex
is another important enzyme that contains a C type heme.
The thioether linkages seem to allow a great freedom of function for the holoproteins. In general, the c type cytochromes can be "fine tuned" over a wider range of oxidation-reduction potential than cytochromes b. This may be an important reason why cytochrome c is nearly ubiquitous throughout life. Heme C also plays an important role in apoptosis
where just a few molecules of cytoplasmic cytochrome c, which must still contain heme C, leads to programmed cell death.
In addition to these covalent bonds, the heme iron is also usually coordinated to two side chains of amino acid
s, making the iron hexacoordinate. For example, mammalian and tuna cytochrome c
contain a single heme C that is coordinated to side chains of both histidine
and methionine
. Perhaps because of the two covalent bonds holding the heme to the protein the iron of heme C is sometimes ligated with the amino group of lysine
or even water.
The correct structure of heme C was published, in mid 20th century, by the Swedish biochemist K.-G. Paul. This work confirmed the structure first inferred by the great Swedish biochemist Hugo Theorell
. The structure of heme C, based upon NMR and IR experiments of the reduced, Fe(II), form of the heme, was confirmed in 1975. The structure of heme C including the absolute stereochemical configuration about the thioether bonds was first presented for the vertebrate protein and is now extended to many other heme C containing proteins.
Heme b
Heme B or haem B is the most abundant heme, both hemoglobin and myoglobin are examples of oxygen transport proteins that contain heme B. The peroxidase family of enzymes also contain heme B...
in that the two vinyl
Vinyl
A vinyl compound is any organic compound that contains a vinyl group ,which are derivatives of ethene, CH2=CH2, with one hydrogen atom replaced with some other group...
side chains of heme B are replaced by covalent, thioether
Thioether
A thioether is a functional group in organosulfur chemistry with the connectivity C-S-C as shown on right. Like many other sulfur-containing compounds, volatile thioethers have foul odors. A thioether is similar to an ether except that it contains a sulfur atom in place of the oxygen...
linkages to the apoprotein
Apoprotein
Apoprotein can refer to:*Apoenzyme, the protein part of an enzyme without its characteristic prosthetic group.*Apolipoprotein, a lipid-binding protein that is a constituent of the plasma lipoprotein....
. These linkages do not allow the heme C to easily dissociate from the holoprotein
Holoprotein
Holoprotein is an apoprotein combined with its prosthetic group....
, cytochrome c
Cytochrome c
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an...
, compared with the more easily dissociated heme B that may dissociate from the holoprotein, the heme-protein complex, even under mild conditions. This allows a very wide range of cytochrome c structure and function, with the myriad of c type cytochromes acting primarily as electron carriers. Cytochromes c, existing as dozens to hundreds of structural and functional subtypes, are found in a wide variety of cell types, even in those organisms living under extreme conditions. While heme B plays a variety of roles in cells, heme C is almost always located in proteins functioning in electron transport reactions most often associated with cell, mitochondria or chloroplast
Chloroplast
Chloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.Chloroplasts are green...
membranes. Heme C, along with the closely structurally related Heme B, are the most common heme types observed in functioning hemeproteins.
The thioether linkages are commonly arranged with two amino acids between the two cysteinyl groups bound to the heme. This is often written as CXXC, within the amino acid sequence presentation with X being most any common amino acid. Vertebrate c type cytochromes also arrange a histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
amino acid next to this sequence so that CXXCH represents the five key amino acids associated with the thioether linkages in these proteins. The two thioether bonds are made to heme ring positions 2 and 4, but a few c type cytochromes have hemes with only a single thioether bond.
The number of heme C units bound to a holoprotein is highly variable. For vertebrate cells one heme C per protein is the rule but for bacteria this number is often 2, 4, 5, 6 or even 16 heme C groups per holoprotein. It is generally agreed the number and arrangement of heme C groups are related and even required for proper holoprotein function. For instance, those proteins containing several heme C groups are involved with multiple electron transfer reactions, particularly important is the 6 electron reduction required to reduce atmospheric nitrogen into two organic ammonia molecules. It is common for the heme C to amino acid ratio to be high for bacterial hemeproteins, so the interiors of some cytochrome c proteins appear packed with many heme C groups compared with other hemeproteins. Some hemeproteins, often from single cell organisms, may contain five hemes C. The bc1 complex
Coenzyme Q - cytochrome c reductase
In enzymology, a ubiquinol—cytochrome-c reductase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are dihydroquinone and ferri- cytochrome c, whereas its 3 products are quinone , ferro- cytochrome c, and H+.This enzyme belongs to the family of...
is another important enzyme that contains a C type heme.
The thioether linkages seem to allow a great freedom of function for the holoproteins. In general, the c type cytochromes can be "fine tuned" over a wider range of oxidation-reduction potential than cytochromes b. This may be an important reason why cytochrome c is nearly ubiquitous throughout life. Heme C also plays an important role in apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
where just a few molecules of cytoplasmic cytochrome c, which must still contain heme C, leads to programmed cell death.
In addition to these covalent bonds, the heme iron is also usually coordinated to two side chains of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s, making the iron hexacoordinate. For example, mammalian and tuna cytochrome c
Cytochrome c
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an...
contain a single heme C that is coordinated to side chains of both histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
and methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
. Perhaps because of the two covalent bonds holding the heme to the protein the iron of heme C is sometimes ligated with the amino group of lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
or even water.
The correct structure of heme C was published, in mid 20th century, by the Swedish biochemist K.-G. Paul. This work confirmed the structure first inferred by the great Swedish biochemist Hugo Theorell
Hugo Theorell
Axel Hugo Theodor Theorell was a Swedish scientist and Nobel Prize laureate in medicine.He was born in Linköping as the son of Thure Theorell and his wife Armida Bill. Theorell went to Secondary School at Katedralskolan in Linköping and passed his examination there on 23 May 1921...
. The structure of heme C, based upon NMR and IR experiments of the reduced, Fe(II), form of the heme, was confirmed in 1975. The structure of heme C including the absolute stereochemical configuration about the thioether bonds was first presented for the vertebrate protein and is now extended to many other heme C containing proteins.
See also
- HemeHemeA heme or haem 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 group; these are...
- Protoporphyrin IXProtoporphyrin IXProtoporphyrin IX, in the metabolism of porphyrin, is created by the enzyme protoporphyrinogen oxidase.-Heme b biosynthesis:In heme biosynthesis, the enzyme ferrochelatase converts it into heme b Protoporphyrin IX, in the metabolism of porphyrin, is created by the enzyme protoporphyrinogen...
- Heme AHeme aHeme A is a heme, a coordination complex consisting of a macrocyclic ligand called a porphyrin, chelating an iron atom. Heme a is a biomolecule and is produced naturally by many organisms.-Relationship to other hemes:...
- Heme BHeme bHeme B or haem B is the most abundant heme, both hemoglobin and myoglobin are examples of oxygen transport proteins that contain heme B. The peroxidase family of enzymes also contain heme B...
- Hemeprotein