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MetaCyc Pathway: heme degradation
Inferred from experiment

Enzyme View:

Pathway diagram: heme degradation

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/AssimilationCofactors, Prosthetic Groups, Electron Carriers DegradationHeme Compounds Degradation

Some taxa known to possess this pathway include : Cavia porcellus, Homo sapiens, Mus musculus

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 [Yamaguchi94].

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 [Yamaguchi94, Komuro96]. .

Created 27-Mar-2008 by Caspi R, SRI International


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

Maines93: Maines MD, Trakshel GM (1993). "Purification and characterization of human biliverdin reductase." Arch Biochem Biophys 300(1);320-6. PMID: 8424666

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

Schuller99: Schuller DJ, Wilks A, Ortiz de Montellano PR, Poulos TL (1999). "Crystal structure of human heme oxygenase-1." Nat Struct Biol 6(9);860-7. PMID: 10467099

Singleton65: Singleton JW, Laster L (1965). "Biliverdin reductase of guinea pig liver." J Biol Chem 240(12);4780-9. PMID: 4378982

Stocker87: Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN (1987). "Bilirubin is an antioxidant of possible physiological importance." Science 235(4792);1043-6. PMID: 3029864

Yamaguchi94: 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

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

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

Dammeyer08: Dammeyer T, Bagby SC, Sullivan MB, Chisholm SW, Frankenberg-Dinkel N (2008). "Efficient phage-mediated pigment biosynthesis in oceanic cyanobacteria." Curr Biol 18(6);442-8. PMID: 18356052

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

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Nakamura03: Nakamura Y, Kaneko T, Sato S, Mimuro M, Miyashita H, Tsuchiya T, Sasamoto S, Watanabe A, Kawashima K, Kishida Y, Kiyokawa C, Kohara M, Matsumoto M, Matsuno A, Nakazaki N, Shimpo S, Takeuchi C, Yamada M, Tabata S (2003). "Complete genome structure of Gloeobacter violaceus PCC 7421, a cyanobacterium that lacks thylakoids." DNA Res 10(4);137-45. PMID: 14621292

Palenik03: Palenik B, Brahamsha B, Larimer FW, Land M, Hauser L, Chain P, Lamerdin J, Regala W, Allen EE, McCarren J, Paulsen I, Dufresne A, Partensky F, Webb EA, Waterbury J (2003). "The genome of a motile marine Synechococcus." Nature 424(6952);1037-42. PMID: 12917641

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

Yoshida88: Yoshida T, Biro P, Cohen T, Muller RM, Shibahara S (1988). "Human heme oxygenase cDNA and induction of its mRNA by hemin." Eur J Biochem 171(3);457-61. PMID: 3345742

Yoshida89: Yoshida T, Sato M (1989). "Posttranslational and direct integration of heme oxygenase into microsomes." Biochem Biophys Res Commun 163(2);1086-92. PMID: 2783112

Zhao06a: Zhao KH, Su P, Li J, Tu JM, Zhou M, Bubenzer C, Scheer H (2006). "Chromophore attachment to phycobiliprotein beta-subunits: phycocyanobilin:cysteine-beta84 phycobiliprotein lyase activity of CpeS-like protein from Anabaena Sp. PCC7120." J Biol Chem 281(13);8573-81. PMID: 16452471

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Sun May 1, 2016, biocyc14.