Biliverdins

Biliverdine [114-25-0] M 582.6, m >300 , pK 3.0. The precursor of bilirubin (above) and forms dark green plates or prisms, with a violet reflection, from MeOH. [Gray et al. J Chem Soc 2264 I961-, Sheldrick J Chem Soc, Perkin Trans 2 1457 1976.]... 

All mammalian cells are virtually capable of producing CO with heme as the main substrate (Fig. 1) [5]. Enzymatic heme metabolism in vivo is mainly catalyzed by heme oxygenase (HO). In the presence of HO, the porphyrin ring of heme is broken and oxidized at the a-methene bridge, producing equimolar amounts of CO, ferrous iron, and biliverdin. Three isoforms of HO have been identified. Inducible HO-1 (32 kDa) is mostly recognized for its upregulation in response... 

Hyjjerbilirubinaemia is an abnormality observed mainly in neonates in whom the liver is insufficiently developed to be able to detoxify the bile pigment bilirubin. This situation is known as neonatal jaundice and can sometimes become a serious disease causing neurotoxic symptoms. Bilirubin is produced by the degradation of heme [the Fe(II) complex of protoporphyrin IX] by heme oxygenase to give biliverdin, which is reduced by biliverdin reductase to... 

In birds and amphibia, the green biliverdin IX is excreted in mammals, a soluble enzyme called biliverdin reductase reduces the methenyl bridge between pyrrole III and pyrrole IV to a methylene group to produce bilirubin, a yellow pigment (Figure 32-12). 

Biliverdin is an early product of catabohsm and on reduction yields bilirubin. The latter is transported by albumin from peripheral tissues to the hver, where it is taken up by hepatocytes. The iron of heme and the amino acids of globin are conserved and reutilized. 

Bile acids The organic acids in bile contains sodium glycocholate and sodium taurocholate, cholesterol, biliverdin and bilirubin, mucus, fat, lecithin, and cells and cellular debris. 

Oxidaton of heme goes through the biliverdin species. Octaethylbiliverdin can exist in coordinated form as the fully reduced trianion (OEB)3-, as the two-electron-oxidized monoanion (OEBox), or as the one-electron-oxidized radical (OEB-)2-. Nickel forms complexes with all three moieties, [Nin(OEB)]ra with n I 1, 0, and -1 (689).1787 The most highly oxidized species [Ni(OEBox)]I3 could be crystallized. The structure shows a helical coordination of the linear tetrapyrrole ligand around nickel with Ni—N distances of 1.867 A and 1.879 A. 

Octaethylbilindione (H3OEB) is a convenient model for the bile pigment biliverdin IXa. Key redox states of this ligand as observed in its complexes are shown in Figure 14. The redox behavior of the palladium complex of octaethylbilindione was examined in order to determine the generality of the redox behavior of this group of transition metal complexes.202 A preliminary report on the novel tetrameric Pd4(OEB)2, which contains palladium) ) ions 7r-bonded to C=C bonds of the tetrapyrrole ligand, and of Pdn(OEB ) has appeared.203... 

S. E. Braslavsky, R. M. Ellul, R. G. Weiss, H.Al-Ekabi, K. Schaffner. Photoprocesses in Biliverdin Dimethyl Ester in Ethanol Studied by Laser-Induced Optoacoustic Spectroscopy (.LIOAS). Tetrahedron 1983, 39, 1909-1913. 

The interaction of linear tetrapyrroles such as biliverdin and bilirubin with nitrogen-oxide-related species has also been investigated by RP-HPLC. Analyses were performed in an ODS... 

H. Kaur, M.N. Hughes, C.J. Green, P. Naughton, R. Foresti and R. Motterlini, Interaction of bilirubin and biliverdin with reactive nitrogen species. FEBS Lett. 543 (2003) 113-119. 

Free haem groups are ferroporphyrins (cyclic tetrapyrroles). The first reaction of haem catabolism is the release of iron this is followed by the opening of the ring to produce a linear tetrapyrrole called biliverdin. A molecule of carbon monoxide is released as the ring opens. Biliverdin is converted to bilirubin by reduction. These initial reactions may occur in the liver or in other tissues of the reticuloendothelial system, notably the spleen. 

Heme metabolized in histiocytes Production of biliverdin releases carbon monoxide (CO)... 

The exact stoichiometric requirements involved in the formation of ferric verdoheme from a-meso-hydroxyheme have been controversial 274-276). Although there is general agreement that this process is oxygen-dependent, the suggestion that additional reducing equivalents are also required 274, 277) has been questioned 275, 276). The conversion of verdoheme to biliverdin is the least well-characterized step of the overall reaction, although a mechanism has been proposed 271). 

Formation of biliverdin or Fe(III)-biliverdin may be dependent on the nature of the reductase, since replacement of the reductase with ascorbate in the HO-catalyzed reaction leads to formation of Fe(III)-biliverdin 282). 

After transfer of heme to MHBP, either directly from hemopexin or from the hemopexin receptor, hemopexin and the receptor both recycle to the surface to undergo further rounds of transport. The heme inside the cell requires further intracellular trafficking to deliver heme to regulatory sites and to HO-1 for catabolism to biliverdin and iron, making intracellular transport an interesting focus of future research. The biliverdin is reduced and excreted as bilirubin, and the iron released, which can also have regulatory effects, is reutilized or stored on ferritin. 

Heme oxygenase catalyzes the first and rate limiting step in the degradation of heme to give biliverdin (Fig. 15). Humans and other mammals have two HO isoforms termed HO-1 and HO-2. Human HO-1 consists of 288 residues (757), whereas rat HO-2 has 316 residues (752). HO contains a C-terminal membrane anchoring sequence (753) that is... 

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