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Heme




A haem or '''heme''' is a prosthetic group that consists of an Iron atom contained in the center of a large Heterocyclic organic ring called a '' Porphyrin ''. Heme groups can bind Oxygen and several biological molecules of crucial importance contain heme groups, most notably the vital Hemoglobin in the body's Red Blood Cell s. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing Metalloprotein s have heme as their prosthetic subunit; these are known as Hemoprotein s.


TYPES

There are three biologically important kinds of heme. The most common type is ''heme b''; the others are ''heme a'' and ''heme c''.
  • ''Heme b'' is not and Myoglobin are examples of proteins that contain heme b.

  • ''Heme a'' differs from heme b in that a Methyl side chain is oxidized into a Formyl group, and one of the Vinyl side chains has been replaced by an Isoprenoid chain. Like heme b, heme a is not covalently bound to the apoprotein in which it is found. An example of a Metalloprotein that has heme a is Cytochrome C Oxidase .

  • ''Heme c'' differs from heme b in that the two vinyl side chains are covalently bound to the protein itself. Examples of proteins that contain a c type heme are Cytochrome C and the Bc1 Complex .


The names of Cytochrome s typically (but not always) reflect the kinds of hemes they contain: cytochrome a contains heme a, cytochrome c contains heme c, etc.


FUNCTION

The main function of heme is the retention of O2 and delivering it for enzymatic reactions. The iron atom of every heme group can bind one molecule of O2. As the main site of oxidation in the Cell is the Mitochondrion , many heme-containing enzymes are located there, and part of the heme synthesis (see below) takes place there.

Hemoglobin is not an enzyme, but a transporter. It binds oxygen in the Pulmonary vasculature, where the PH is high and the pCO2 is low, and releases it in the tissues, where the situations are reversed. The main mechanism behind this phenomenon is the steric organisation of the globin chain; a Histidine residue, located adjacent to the heme group, becomes positively charged under acid circumstances, sterically releasing oxygen from the heme group.


SYNTHESIS

''Details of heme synthesis can be found in the article on Porphyrin .''

and Mitochondrion .]]


The enzymatic process that produces heme is properly called Porphyrin synthesis, as all the intermediates are Tetrapyrrole s that are chemically classified are 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 in patients with an Inborn Error Of Metabolism of this process, by reducing transcription of ALA synthase.

The organs mainly involved in heme synthesis are the Liver and the Bone Marrow , although every cell requires heme to function properly.


Genes

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

  • '' ALAD '': aminolevulinic acid, delta-, dehydratase

  • '' ALAS1 '': aminolevulinate, delta-, synthase 1

  • '' ALAS2 '': aminolevulinate, delta-, synthase 2 (sideroblastic/hypochromic anemia)

  • '' CPOX '': coproporphyrinogen oxidase

  • '' FECH '': ferrochelatase (protoporphyria)

  • '' HMBS '': hydroxymethylbilane synthase

  • '' PPOX '': protoporphyrinogen oxidase

  • '' UROD '': uroporphyrinogen decarboxylase

  • '' UROS '': uroporphyrinogen III synthase (congenital erythropoietic porphyria)



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