Heme a
Encyclopedia
Heme 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.
in that a methyl side chain
at ring position 8 is oxidized to a formyl group and a hydroxyethylfarnesyl group
, an isoprenoid
chain, has been attached to the vinyl
side chain at ring position 3 of the iron tetrapyrrole heme
. Heme A is similar to heme o
, in that both have this farnesyl addition at position 3 but heme O does not have the formyl group at position 8, still containing the methyl group. The correct structure of heme A, based upon NMR and IR experiments of the reduced, Fe(II), form of the heme, was published in 1975.
cytochrome c oxidase.
Like heme B, heme A is often attached to the apoprotein through a coordinate bond between the heme iron and a conserved amino acid side-chain. In the important respiratory protein cytochrome c oxidase
(CCO) this ligand 5 for the heme A at the oxygen reaction center is a histidyl group. This is a common ligand for many hemeproteins including hemoglobin
and myoglobin
.
Heme a in cyctochrome c oxidase, bound by two histidine
residues (shown in pink)
An example of a metalloprotein that contains heme A is cytochrome c oxidase. This very complicated protein contains heme A at two different sites, each with a different function. The iron of the heme A of cytochrome a is hexacoordinated, that is bound with 6 other atoms. The iron of the heme A of cytochrome a3 is sometimes bound by 5 other atoms leaving the sixth site available to bind dioxygen (molecular oxygen
). In addition, this enzyme binds 3 copper, magnesium, zinc, and several potassium and sodium ions. The two heme A groups in CCO are thought to readily exchange electrons between each other, the copper ions and the closely associated protein cytochrome c.
Both the formyl group and the isoprenoid
side chain are thought to play important roles in conservation of the energy of oxygen reduction by cytochrome c oxidase
. CCO is thought to be responsible for conserving the energy of dioxygen reduction by pumping protons into the inner mitochondrial space. Both the formyl and hydroxyethylfarnesyl groups of heme A are thought to play important roles in this critical process, as published by the influential group of S. Yoshikawa.
Heme
A 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...
, a coordination complex consisting of a macrocyclic
Macrocycle
A macrocycle is, as defined by IUPAC, "a cyclic macromolecule or a macromolecular cyclic portion of a molecule." In the chemical literature, organic chemists may consider any molecule containing a ring of nine or more atoms to be a macrocycle...
ligand called a porphyrin
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
, chelating
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....
an iron atom. Heme a is a biomolecule
Biomolecule
A biomolecule is any molecule that is produced by a living organism, including large polymeric molecules such as proteins, polysaccharides, lipids, and nucleic acids as well as small molecules such as primary metabolites, secondary metabolites, and natural products...
and is produced naturally by many organisms.
Relationship to other hemes
Heme A differs from heme BHeme 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 a methyl side chain
Side chain
In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called "main chain" or backbone. The placeholder R is often used as a generic placeholder for alkyl group side chains in chemical structure diagrams. To indicate other non-carbon...
at ring position 8 is oxidized to a formyl group and a hydroxyethylfarnesyl group
Farnesene
The term farnesene refers to a set of six closely related chemical compounds which all are sesquiterpenes. α-Farnesene and β-farnesene are isomers, differing by the location of one double bond. α-Farnesene is 3,7,11-trimethyl-1,3,6,10-dodecatetraene and β-farnesene is...
, an isoprenoid
Isoprene
Isoprene , or 2-methyl-1,3-butadiene, is a common organic compound with the formula CH2=CCH=CH2. Under standard conditions it is a colorless liquid...
chain, has been attached to the 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 chain at ring position 3 of the iron tetrapyrrole heme
Heme
A 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...
. Heme A is similar to heme o
Heme o
Heme O differs from the closely related heme A by having a methyl group at ring position 8 instead of the formyl group. The isoprenoid chain at position 2 is the same....
, in that both have this farnesyl addition at position 3 but heme O does not have the formyl group at position 8, still containing the methyl group. The correct structure of heme A, based upon NMR and IR experiments of the reduced, Fe(II), form of the heme, was published in 1975.
History
Heme A was first isolated by the great German biochemist Otto Warburg in 1951 and shown by him to be the active component of the integral membrane metalloproteinMetalloprotein
Metalloprotein is a generic term for a protein that contains a metal ion cofactor. Metalloproteins have many different functions in cells, such as enzymes, transport and storage proteins, and signal transduction proteins. Indeed, about one quarter to one third of all proteins require metals to...
cytochrome c oxidase.
Stereochemistry
The final structural question of the exact geometric configuration about the first carbon at ring position 3 of ring I, the carbon bound to the hydroxyl group, has been recently published as the chiral S configuration.Like heme B, heme A is often attached to the apoprotein through a coordinate bond between the heme iron and a conserved amino acid side-chain. In the important respiratory protein cytochrome c oxidase
Cytochrome c oxidase
The enzyme cytochrome c oxidase or Complex IV is a large transmembrane protein complex found in bacteria and the mitochondrion.It is the last enzyme in the respiratory electron transport chain of mitochondria located in the mitochondrial membrane...
(CCO) this ligand 5 for the heme A at the oxygen reaction center is a histidyl group. This is a common ligand for many hemeproteins including hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
and myoglobin
Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the...
.
Heme a in cyctochrome c oxidase, bound by two 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...
residues (shown in pink)
An example of a metalloprotein that contains heme A is cytochrome c oxidase. This very complicated protein contains heme A at two different sites, each with a different function. The iron of the heme A of cytochrome a is hexacoordinated, that is bound with 6 other atoms. The iron of the heme A of cytochrome a3 is sometimes bound by 5 other atoms leaving the sixth site available to bind dioxygen (molecular oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
). In addition, this enzyme binds 3 copper, magnesium, zinc, and several potassium and sodium ions. The two heme A groups in CCO are thought to readily exchange electrons between each other, the copper ions and the closely associated protein cytochrome c.
Both the formyl group and the isoprenoid
Isoprene
Isoprene , or 2-methyl-1,3-butadiene, is a common organic compound with the formula CH2=CCH=CH2. Under standard conditions it is a colorless liquid...
side chain are thought to play important roles in conservation of the energy of oxygen reduction by cytochrome c oxidase
Cytochrome c oxidase
The enzyme cytochrome c oxidase or Complex IV is a large transmembrane protein complex found in bacteria and the mitochondrion.It is the last enzyme in the respiratory electron transport chain of mitochondria located in the mitochondrial membrane...
. CCO is thought to be responsible for conserving the energy of dioxygen reduction by pumping protons into the inner mitochondrial space. Both the formyl and hydroxyethylfarnesyl groups of heme A are thought to play important roles in this critical process, as published by the influential group of S. Yoshikawa.
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...
- HemoproteinHemoproteinA hemeprotein , or heme protein, is a metalloprotein containing a heme prosthetic group- an organic compound that allows a protein to carry out a function that it cannot do alone....
- Cytochrome c oxidaseCytochrome c oxidaseThe enzyme cytochrome c oxidase or Complex IV is a large transmembrane protein complex found in bacteria and the mitochondrion.It is the last enzyme in the respiratory electron transport chain of mitochondria located in the mitochondrial membrane...
(Complex IV of cellular respirationCellular respirationCellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...
)