This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Degradation/Utilization/Assimilation → Cofactors, Prosthetic Groups, Electron Carriers Degradation → Heme Compounds Degradation|
Expected Taxonomic Range: Eukaryota
The heme degradation pathway in animals ensures the recycling of iron. The first enzyme in this pathway, heme oxygenase 1, catayzes the opening of the tetrapyrrole macrocycle of heme b, forming biliverdin-IX-α, Fe2+, and carbon monoxide. The enzyme, which uses heme as both a substrate and a cofactor, has been purified from humans and crystalized [Schuller99].
biliverdin-IX-α is then reduced to bilirubin by biliverdin reductase. This cytosolic enzyme was originally discovered in Guinea pig liver [Singleton65], and has been characterized from several mammals, including rat and humans [Maines93, Maines96]. Two forms of biliverdin-IX α reductase and two forms of biliverdin-IX β reductase have been purified from human liver [Yamaguchi94a].
Bilirubin is an erfective chain-breaking antioxidant in vitro [Stocker87], although has been questioned whether if fulfills this role in vivo [Fauchere94]. Proposed roles for bilirubin in vivo include a scavenger of nitric oxide [Mancuso03] and an endogenous modulator of neurotrophin redox signaling [Mancuso08]. Bilirubin is secreted into the bile, and eventually excreted.
It should be noted that while most of the bilirubin in adult humans is the α form, it is the β form that predominates in fetal bile. Other enzymes are responsible for the degradation of the β form [Yamaguchi94a, Komuro96]. .
Fauchere94: Fauchere JC, Meier-Gibbons FE, Koerner F, Bossi E (1994). "Retinopathy of prematurity and bilirubin--no clinical evidence for a beneficial role of bilirubin as a physiological anti-oxidant." Eur J Pediatr 153(5);358-62. PMID: 8033927
Komuro96: Komuro A, Tobe T, Hashimoto K, Nakano Y, Yamaguchi T, Nakajima H, Tomita M (1996). "Molecular cloning and expression of human liver biliverdin-IX beta reductase." Biol Pharm Bull 19(6);796-804. PMID: 8799475
Maines96: Maines MD, Polevoda BV, Huang TJ, McCoubrey WK (1996). "Human biliverdin IXalpha reductase is a zinc-metalloprotein. Characterization of purified and Escherichia coli expressed enzymes." Eur J Biochem 235(1-2);372-81. PMID: 8631357
Mancuso03: Mancuso C, Bonsignore A, Di Stasio E, Mordente A, Motterlini R (2003). "Bilirubin and S-nitrosothiols interaction: evidence for a possible role of bilirubin as a scavenger of nitric oxide." Biochem Pharmacol 66(12);2355-63. PMID: 14637193
Mancuso08: Mancuso C, Capone C, Ranieri SC, Fusco S, Calabrese V, Eboli ML, Preziosi P, Galeotti T, Pani G (2008). "Bilirubin as an endogenous modulator of neurotrophin redox signaling." J Neurosci Res NIL. PMID: 18338802
Yamaguchi94a: Yamaguchi T, Komoda Y, Nakajima H (1994). "Biliverdin-IX alpha reductase and biliverdin-IX beta reductase from human liver. Purification and characterization." J Biol Chem 269(39);24343-8. PMID: 7929092
Cornejo98: Cornejo J, Willows RD, Beale SI (1998). "Phytobilin biosynthesis: cloning and expression of a gene encoding soluble ferredoxin-dependent heme oxygenase from Synechocystis sp. PCC 6803." Plant J 15(1);99-107. PMID: 9744099
Emborg06: Emborg TJ, Walker JM, Noh B, Vierstra RD (2006). "Multiple heme oxygenase family members contribute to the biosynthesis of the phytochrome chromophore in Arabidopsis." Plant Physiol 140(3);856-68. PMID: 16428602
Gisk10: Gisk B, Yasui Y, Kohchi T, Frankenberg-Dinkel N (2010). "Characterization of the haem oxygenase protein family in Arabidopsis thaliana reveals a diversity of functions." Biochem J 425(2);425-34. PMID: 19860740
Willows00: Willows RD, Mayer SM, Foulk MS, DeLong A, Hanson K, Chory J, Beale SI (2000). "Phytobilin biosynthesis: the Synechocystis sp. PCC 6803 heme oxygenase-encoding ho1 gene complements a phytochrome-deficient Arabidopsis thalianna hy1 mutant." Plant Mol Biol 43(1);113-20. PMID: 10949378
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