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MetaCyc Pathway: heme biosynthesis I (aerobic)
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: heme biosynthesis I (aerobic)

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: BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisPorphyrin Compounds BiosynthesisHeme Biosynthesis

Some taxa known to possess this pathway include : Agrobacterium tumefaciens, Arabidopsis thaliana col, Bacillus subtilis subtilis 168, Escherichia coli K-12 substr. MG1655, Euglena gracilis, Homo sapiens, Mammalia, Mus musculus, Nicotiana tabacum, Plasmodium falciparum, Rhizobiaceae, Rhodobacter sphaeroides, Saccharomyces cerevisiae, Synechocystis sp. PCC 6803

Expected Taxonomic Range: Bacteria , Eukaryota

General Background

Heme (protoheme, heme b) is an iron-containing prosthetic group found in many essential proteins including cytochromes and heme-containing globins. In addition to its role in oxidative metabolism, heme also functions as a regulatory molecule in transcription, translation, protein targeting, protein stability, and cellular differentiation.

Heme is a porphyrin member of the cyclic tetrapyrroles. Even though it is biosynthesized as heme b, different derivatives of protoheme can be formed that differ in modifications to the porphyrin ring, including how it is bound to the protein, such as heme o, heme a, heme c, and heme d.

About This Pathway

This pathway describes the common aerobic route for heme b biosynthesis. This pathway involves the enzymes coproporphyrinogen III oxidase and protoporphyrinogen oxidase, which require moelecular oxygen for their respective reactions.

There are several types of protoporphyrinogen oxidases: in most eukaryotes and many aerobic or facultative bacteria, such as Firmicutes, the enzyme is a FAD-dependent ~55 kDa protein encoded by the hemY gene. A number of γ-proteobacteria, including Escherichia coli, have another type of oxidase, a 21 kDa protein encoded by the hemG gene. Most archaea and many other bacteria, including the majority of cyanobacteria, have a third version of the enzyme, a 24 kDa protein encoded by hemJ [Kato10].

Citations: [Overbeek98, Christie04, Yeh04, Romero05]

Superpathways: superpathway of heme biosynthesis from glycine, superpathay of heme biosynthesis from glutamate

Variants: heme biosynthesis II (anaerobic), heme biosynthesis III (from siroheme), heme d1 biosynthesis, superpathway of heme biosynthesis from uroporphyrinogen-III


Created 12-Jun-1998 by Ying HC, SRI International
Revised 04-Nov-2005 by Fulcher CA, SRI International
Revised 15-May-2006 by Caspi R, SRI International


Caughey75: Caughey WS, Smythe GA, O'Keeffe DH, Maskasky JE, Smith MI (1975). "Heme A of cytochrome c oxicase. Structure and properties: comparisons with hemes B, C, and S and derivatives." J Biol Chem 250(19);7602-22. PMID: 170266

Christie04: Christie KR, Weng S, Balakrishnan R, Costanzo MC, Dolinski K, Dwight SS, Engel SR, Feierbach B, Fisk DG, Hirschman JE, Hong EL, Issel-Tarver L, Nash R, Sethuraman A, Starr B, Theesfeld CL, Andrada R, Binkley G, Dong Q, Lane C, Schroeder M, Botstein D, Cherry JM (2004). "Saccharomyces Genome Database (SGD) provides tools to identify and analyze sequences from Saccharomyces cerevisiae and related sequences from other organisms." Nucleic Acids Res 32(Database issue);D311-4. PMID: 14681421

Frankenberg03: Frankenberg N, Moser J, Jahn D (2003). "Bacterial heme biosynthesis and its biotechnological application." Appl Microbiol Biotechnol 63(2);115-27. PMID: 13680202

Kato10: Kato K, Tanaka R, Sano S, Tanaka A, Hosaka H (2010). "Identification of a gene essential for protoporphyrinogen IX oxidase activity in the cyanobacterium Synechocystis sp. PCC6803." Proc Natl Acad Sci U S A 107(38);16649-54. PMID: 20823222

Overbeek98: Overbeek, R, Larsen, N, Selkov, EE, Maltsev, M "The WIT Database." 1998 WWW URL http://www.cme.msu.edu/WIT/.

Panek02: Panek H, O'Brian MR (2002). "A whole genome view of prokaryotic haem biosynthesis." Microbiology 148(Pt 8);2273-82. PMID: 12177321

Romero05: Romero P, Wagg J, Green ML, Kaiser D, Krummenacker M, Karp PD (2005). "Computational prediction of human metabolic pathways from the complete human genome." Genome Biol 6(1);R2. PMID: 15642094

Warburg51: Warburg O, Gewitz HS (1951). "Cytohamin aus Herzmuskel." Hoppe-Seyler´s Zeitschrift für physiologische Chemie 288(1);1-4.

Yeh04: Yeh I, Hanekamp T, Tsoka S, Karp PD, Altman RB (2004). "Computational analysis of Plasmodium falciparum metabolism: organizing genomic information to facilitate drug discovery." Genome Res 14(5);917-24. PMID: 15078855

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

Boynton09: Boynton TO, Daugherty LE, Dailey TA, Dailey HA (2009). "Identification of Escherichia coli HemG as a novel, menadione-dependent flavodoxin with protoporphyrinogen oxidase activity." Biochemistry 48(29):6705-11. PMID: 19583219

Boynton11: Boynton TO, Gerdes S, Craven SH, Neidle EL, Phillips JD, Dailey HA (2011). "Discovery of a gene involved in a third bacterial protoporphyrinogen oxidase activity through comparative genomic analysis and functional complementation." Appl Environ Microbiol 77(14);4795-801. PMID: 21642412

Breckau03: Breckau D, Mahlitz E, Sauerwald A, Layer G, Jahn D (2003). "Oxygen-dependent coproporphyrinogen III oxidase (HemF) from Escherichia coli is stimulated by manganese." J Biol Chem 278(47);46625-31. PMID: 12975365

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Brenner92: Brenner DA, Didier JM, Frasier F, Christensen SR, Evans GA, Dailey HA (1992). "A molecular defect in human protoporphyria." Am J Hum Genet 50(6);1203-10. PMID: 1376018

Cacheux94: Cacheux V, Martasek P, Fougerousse F, Delfau MH, Druart L, Tachdjian G, Grandchamp B (1994). "Localization of the human coproporphyrinogen oxidase gene to chromosome band 3q12." Hum Genet 94(5);557-9. PMID: 7959694

Cantley75: Cantley LC, Hammes GG (1975). "Characterization of nucleotide binding sites on chloroplast coupling factor 1." Biochemistry 14(13);2968-75. PMID: 1148187

Cantoni84: Cantoni L, Dal Fiume D, Ruggieri R (1984). "Decarboxylation of uroporphyrinogen I and III in 2,3,7,8-tetrachlorodibenzo-p-dioxin induced porphyria in mice." Int J Biochem 16(5);561-5. PMID: 6724109

Colloch02: Colloc'h N, Mornon JP, Camadro JM (2002). "Towards a new T-fold protein?: the coproporphyrinogen III oxidase sequence matches many structural features from urate oxidase." FEBS Lett 526(1-3);5-10. PMID: 12208494

Corrigall98: Corrigall AV, Siziba KB, Maneli MH, Shephard EG, Ziman M, Dailey TA, Dailey HA, Kirsch RE, Meissner PN (1998). "Purification of and kinetic studies on a cloned protoporphyrinogen oxidase from the aerobic bacterium Bacillus subtilis." Arch Biochem Biophys 358(2);251-6. PMID: 9784236

Dailey00: Dailey HA, Dailey TA, Wu CK, Medlock AE, Wang KF, Rose JP, Wang BC (2000). "Ferrochelatase at the millennium: structures, mechanisms and [2Fe-2S] clusters." Cell Mol Life Sci 57(13-14);1909-26. PMID: 11215517

Dailey02: Dailey TA, Dailey HA (2002). "Identification of [2Fe-2S] clusters in microbial ferrochelatases." J Bacteriol 184(9);2460-4. PMID: 11948160

Dailey86a: Dailey HA (1986). "Purification and characterization of bacterial ferrochelatase." Methods Enzymol 123;408-15. PMID: 3702737

Dailey94: Dailey HA, Sellers VM, Dailey TA (1994). "Mammalian ferrochelatase. Expression and characterization of normal and two human protoporphyric ferrochelatases." J Biol Chem 269(1);390-5. PMID: 8276824

Dailey96: Dailey HA, Dailey TA (1996). "Protoporphyrinogen oxidase of Myxococcus xanthus. Expression, purification, and characterization of the cloned enzyme." J Biol Chem 271(15);8714-8. PMID: 8621504

Dailey96a: Dailey TA, Dailey HA (1996). "Human protoporphyrinogen oxidase: expression, purification, and characterization of the cloned enzyme." Protein Sci 5(1);98-105. PMID: 8771201

deVerneuil92: de Verneuil H, Bourgeois F, de Rooij F, Siersema PD, Wilson JH, Grandchamp B, Nordmann Y (1992). "Characterization of a new mutation (R292G) and a deletion at the human uroporphyrinogen decarboxylase locus in two patients with hepatoerythropoietic porphyria." Hum Genet 89(5);548-52. PMID: 1634232

Deybach85: Deybach JC, da Silva V, Grandchamp B, Nordmann Y (1985). "The mitochondrial location of protoporphyrinogen oxidase." Eur J Biochem 149(2);431-5. PMID: 3996415

Deybach96: Deybach JC, Puy H, Robreau AM, Lamoril J, Da Silva V, Grandchamp B, Nordmann Y (1996). "Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria." Hum Mol Genet 5(3);407-10. PMID: 8852667

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

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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.