Heme

Häme are complex compounds with an iron ion as the central atom and a porphyrin molecule as a ligand. The best-known representative is the Fe - protoporphyrin IX, also called " heme b" or simply called " heme ". Malice can be found as a prosthetic group in several groups of proteins, including the globins and cytochromes.

Heme b is a ferruginous pigment of red blood cells. Together with the present in the erythrocyte protein, globin, it forms hemoglobin, which plays a central role in the oxygen uptake of the body. Other Häme as heme b are found in bacteria and plants.

Members

Häme are iron-containing porphyrin. The Häme in the strict sense, first differ in the functional groups attached to the porphyrin.

While heme c is covalently bonded to the thiol groups of cysteine ​​residues in the protein, it is the case with heme a and b on non -covalent manner. Otherwise, heme does not distinguish b and c. By replacement of certain amino acids in the cysteine ​​-bound protein b / c hybrids can be produced, which have different properties.

More counting the hemes compounds are

• Heme d,
• Heme d1, the prosthetic group of cytochrome cd1, a bacterial nitrite reductase ( EC 1.7.2.1 )
• P460 heme, the prosthetic group of the hydroxylamine oxidoreductase in Nitrosomonas europaea ( EC 1.7.3.4 )
• Sirohäm, the prosthetic group of ferredoxin - nitrite reductase in plants, algae and cyanobacteria ( EC 1.7.7.1 ), and the bacterial and plant Sulfitreduktasen ( EC 1.8.1.2 and EC 1.8.7.1 )

Structural formula of heme b

Structural formula of heme c

Molecular structure of heme d

Molecular structure of heme d1

Structural formula of heme o

Molecular structure of heme P460

Structural formula of the Sirohäms

Physiology

Häme are synthesized in living organisms from the porphyrins. In contrast, the degradation pathways lead via biliverdin and bilirubin to not degradable tetrapyrroles ( Bilenen ), which are excreted.

Biosynthesis

In the human body the biosynthesis of all porphyrins of succinyl -CoA and the amino acid glycine goes out. The first step leads to the δ - aminolevulinate. Plants, algae, bacteria ( with the exception of Alphaproteobacterien ) and Archeaebakterien can also be prepared from glutamic acid producing what is known as C5 - or δ - aminolevulinate Beale pathway. Four of these molecules are converted to Hydroxymethylbilan. Other transformations take place gradually over uroporphyrinogen III and coproporphyrinogen III to protoporphyrinogen IX and protoporphyrin IX. For details see the biosynthesis of porphyrins.

Heme b is formed by the incorporation of ferrous iron into protoporphyrin IX using the enzyme ferrochelatase.

Fe2 ⇔ 2H

A heme as part of the cytochrome c oxidase is produced in humans, in two steps from heme b. By means of the mitochondrial protoheme IX farnesyltransferase ( COX10 ) initially produces heme o, which is hydroxylated by means of another enzyme called COX15 in the 18- position; as cofactors are necessary ferredoxin and the corresponding ferredoxin reductase. The last step of conversion to the aldehyde is catalyzed by an unknown enzyme in the human, which has been identified as the gene product of Bacillus subtilis CTAA gene.

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Degradation and excretion

The degradation products of heme hot bile pigments.

The heme oxygenase converts heme nor the red in the blood under demolition of the porphyrin ring and iron and elimination of carbon monoxide to the green biliverdin to. Galle features a typical yellowish to greenish color, depending on the changing content of biliverdin and bilirubin orange and red; the latter is produced by biliverdin reductase by reduction of biliverdin. The bile pigments are Eliminated mainly in the urine ( as yellow to orange Urochrome stercobilin, urobilinogen and urobilin ), or the feces (as Koprochrome also stercobilin, Bilifuscin and Mesobilifuscin ).

Even more degradation products of bilirubin as the colorless Sterkobilinogen ( which is converted by intestinal bacteria to brown Dipyrrolen Mesobilifuchsin and Bilifuchsin ) contribute to the normal stool color at. Partial Bilirubinabbauprodukte be reabsorbed and excreted in the urine.

Pathology

Each of the enzymes involved in the biosynthesis and degradation in may have a defect, resulting in each case of a typical hereditary ( rare ) metabolic disease. The defects occurring during the Porphyrinbiosynthese as well as the ferrochelatase deficiency are grouped under the name porphyria. Defects in heme -a synthesis, ie COX -10 and COX -15 deficiency, however, lead to Leigh syndrome.