On Air


Buy this Domain?
Do you interesting about this domain and the running project?
Feel free to send your offer to webmaster.
pay with Paypal



Heme or haem is a coordination complex "consisting of an iron ion coordinated to a porphyrin acting as a tetradentate ligand, and to one or two axial ligands."https://goldbook.iupac.org/html/H/H02773.html The definition is loose, and many depictions omit the axial ligands.A standard biochemistry text defines heme as the "iron-porphyrin prosthetic group of heme proteins"(Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. .) Many porphyrin-containing metalloproteins have heme as their prosthetic group; these are known as hemoproteins. Hemes are most commonly recognized as components of hemoglobin, the red pigment in blood, but are also found in a number of other biologically important hemoproteins such as myoglobin, cytochromes, catalases, heme peroxidase, and endothelial nitric oxide synthase. The word heme is derived from Greek haima meaning blood.


Hemoproteins have diverse biological functions including the transportation of diatomic gases, chemical catalysis, diatomic gas detection, and electron transfer. The heme iron serves as a source or sink of electrons during electron transfer or redox chemistry. In peroxidase reactions, the porphyrin molecule also serves as an electron source. In the transportation or detection of diatomic gases, the gas binds to the heme iron. During the detection of diatomic gases, the binding of the gas ligand to the heme iron induces conformational changes in the surrounding protein. In general, diatomic gases only bind to the reduced heme, as ferrous Fe(II) while most peroxidases cycle between Fe(III) and Fe(IV) and hemeproteins involved in mitochondrial redox, oxidation-reduction, cycle between Fe(II) and Fe(III). It has been speculated that the original evolutionary function of hemoproteins was electron transfer in primitive sulfur-based photosynthesis pathways in ancestral cyanobacteria-like organisms before the appearance of molecular oxygen. Hemoproteins achieve their remarkable functional diversity by modifying the environment of the heme macrocycle within the protein matrix. For example, the ability of hemoglobin to effectively deliver oxygen to tissues is due to specific amino acid residues located near the heme molecule. Hemoglobin reversibly binds to oxygen in the lungs when the pH is high, and the carbon dioxide concentration is low. When the situation is reversed (low pH and high carbon dioxide concentrations), hemoglobin will release oxygen into the tissues. This phenomenon, which states that hemoglobin's oxygen binding affinity is inversely proportional to both acidity and concentration of carbon dioxide, is known as the Bohr effect. The molecular mechanism behind this effect is the steric organization of the globin chain; a histidine residue, located adjacent to the heme group, becomes positively charged under acidic conditions (which are caused by dissolved CO2 in working muscles, etc.) releasing oxygen from the heme group.


Major hemes

There are several biologically important kinds of heme: The most common type is heme B; other important types include heme A and heme C. Isolated hemes are commonly designated by capital letters while hemes bound to proteins are designated by lower case letters. Cytochrome a refers to the heme A in specific combination with membrane protein forming a portion of cytochrome c oxidase.

Other hemes

The following carbon numbering system of porphyrins is an older numbering used by biochemists and not the 1–24 numbering system recommended by IUPAC which is shown in the table above.
  • Heme l is the derivative of heme B which is covalently attached to the protein of lactoperoxidase, eosinophil peroxidase, and thyroid peroxidase. The addition of peroxide with the glutamyl-375 and aspartyl-225 of lactoperoxidase forms ester bonds between these amino acid residues and the heme 1- and 5-methyl groups, respectively. Similar ester bonds with these two methyl groups are thought to form in eosinophil and thyroid peroxidases. Heme l is one important characteristic of animal peroxidases; plant peroxidases incorporate heme B. Lactoperoxidase and eosinophil peroxidase are protective enzymes responsible for the destruction of invading bacteria and virus. Thyroid peroxidase is the enzyme catalyzing the biosynthesis of the important thyroid hormones. Because lactoperoxidase destroys invading organisms in the lungs and excrement, it is thought to be an important protective enzyme.
  • Heme m is the derivative of heme B covalently bound at the active site of peroxide. Heme m contains the two ester bonds at the heme 1- and 5-methyls as in heme l found in other mammalian peroxides. In addition, a unique sulfonamides ion linkage between the sulfur of a methionyl amino-acid residue and the heme 2-vinyl group is formed, giving this enzyme the unique capability of easily oxidizing chloride and bromide ions. Myeloperoxidase is present in mammalian neutrophils and is responsible for the destruction of invading bacteria and viruse. It also synthesizes hypobromite by "mistake" which is a known mutagenic compound.
  • Heme D is another derivative of heme B, but in which the propionic acid side chain at the carbon of position 6, which is also hydroxylated, forms a γ- spirolactone. Ring III is also hydroxylated at position 5, in a conformation trans to the new lactone group. Heme D is the site for oxygen reduction to water of many types of bacteria at low oxygen tension.
  • Heme S is related to heme B by having a formal group at position 2 in place of the 2-vinyl group. Heme S is found in the hemoglobin of marine worms. The correct structures of heme B and heme S were first elucidated by German chemist Hans Fischer.
The names of cytochromes typically (but not always) reflect the kinds of hemes they contain: cytochrome a contains heme A, cytochrome c contains heme C, etc. This convention may have been first introduced with the publication of the structure of heme A.


The enzymatic process that produces heme is properly called porphyrin synthesis, as all the intermediates are tetrapyrroles that are chemically classified as porphyrins. The process is highly conserved across biology. In humans, this pathway serves almost exclusively to form heme. In other species, it also produces similar substances such as cobalamin ( vitamin B12). The pathway is initiated by the synthesis of D-aminolevulinic acid (dALA or δALA) from the amino acid glycine and succinyl-CoA from the citric acid cycle (Krebs cycle). The rate-limiting enzyme responsible for this reaction, ALA synthase, is negatively regulated by glucose and heme concentration. Mechanism of inhibition of ALAs by heme or hemin is by decreasing stability of mRNA synthesis and by decreasing the intake of mRNA in the mitochondria. This mechanism is of therapeutic importance: infusion of heme arginate or hematin and glucose can abort attacks of acute intermittent porphyria in patients with an inborn error of metabolism of this process, by reducing transcription of ALA synthase.http://escholarship.umassmed.edu/gsbs_diss/121/ The organs mainly involved in heme synthesis are the liver (in which the rate of synthesis is highly variable, depending on the systemic heme pool) and the bone marrow (in which rate of synthesis of Heme is relatively constant and depends on the production of globin chain), although every cell requires heme to function properly. However, due to its toxic properties, proteins such as Hemopexin (Hx) are required to help maintain physiological stores of iron in order for them to be used in synthesis. Heme is seen as an intermediate molecule in catabolism of hemoglobin in the process of bilirubin metabolism. Defects in various enzymes in synthesis of heme can lead to group of disorder called porphyrias, these include acute intermittent porphyria, congenital erythropoetic porphyria, porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria, erythropoietic protoporphyria.


Degradation begins inside macrophages of the spleen, which remove old and damaged (senescent) erythrocytes from the circulation. In the first step, heme is converted to biliverdin by the enzyme heme oxygenase (HMOX). NADPH is used as the reducing agent, molecular oxygen enters the reaction, carbon monoxide (CO) is produced and the iron is released from the molecule as the ferrous ion (Fe2+). CO acts as a cellular messenger and functions in vasodilation. In addition, heme degradation appears to be an evolutionarily-conserved response to oxidative stress. Briefly, when cells are exposed to free radicals, there is a rapid induction of the expression of the stress-responsive heme oxygenase-1 (HMOX1) isoenzyme that catabolizes heme (see below). The reason why cells must increase exponentially their capability to degrade heme in response to oxidative stress remains unclear but this appears to be part of a cytoprotective response that avoids the deleterious effects of free heme. When large amounts of free heme accumulates, the heme detoxification/degradation systems get overwhelmed, enabling heme to exert its damaging effects.


The following genes are part of the chemical pathway for making heme:

See also

Notes and references

"green air" © 2007 - Ingo Malchow, Webdesign Neustrelitz
This article based upon the http://en.wikipedia.org/wiki/Heme, the free encyclopaedia Wikipedia and is licensed under the GNU Free Documentation License.
Further informations available on the list of authors and history: http://en.wikipedia.org/w/index.php?title=Heme&action=history
presented by: Ingo Malchow, Mirower Bogen 22, 17235 Neustrelitz, Germany