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MetaCyc Pathway: superpathay of heme biosynthesis from glutamate
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: superpathay of heme biosynthesis from glutamate

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 : Arabidopsis thaliana col, Escherichia coli K-12 substr. MG1655, Euglena gracilis, Nicotiana tabacum, Pseudomonas denitrificans, Salmonella enterica enterica serovar Typhimurium, Triticum aestivum

Expected Taxonomic Range: Archaea, Euglenozoa, Magnoliophyta, Proteobacteria

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.

The protoheme biosynthetic pathway shown here is found in some bacteria (including Escherichia coli K-12), archaea, and plants. In these organisms the tetrapyrrole biosynthesis pathway starts with glutamate (see tetrapyrrole biosynthesis I (from glutamate)).

In many other organisms, including animals, fungi, apicomplexan protozoa (such as the malaria parasite Plasmodium falciparum [Sato04]), and members of the α-proteobacteria, the tetrapyrrole biosynthesis pathway starts with glycine and succinyl-CoA (see tetrapyrrole biosynthesis II (from glycine)). Both the glycine and glutamate pathways are present in the chloroplast-containing Euglena gracilis (reviewed in [Frankenberg03, Moraes04, Wilson02, Obornik05]).

Both tetrapyrrole biosynthetic pathways merge at the intermediate 5-aminolevulinate. However, a branch point at uroporphyrinogen-III leads to biosynthesis of different compounds such as vitamin B12 (cobalamin) (see adenosylcobalamin biosynthesis II (aerobic)), oxidized coenzyme F430 (see factor 430 biosynthesis), siroheme (see siroheme biosynthesis), and heme D biosynthesis. A second branch point at protoporphyrin IX leads to biosynthesis of chlorophyll in plants and bacteriochlorophyll in photosynthetic bacteria (see chlorophyllide a biosynthesis I (aerobic, light-dependent)). In eukaryotes, heme biosynthesis spans the mitochondrial (or plastid) and cytosol compartments.

This topic has been reviewed in [Frankenberg03, Panek02, Obornik05].

Subpathways: heme biosynthesis I (aerobic), tetrapyrrole biosynthesis I (from glutamate)

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

Created 07-May-2008 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

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

Moraes04: Moraes CT, Diaz F, Barrientos A (2004). "Defects in the biosynthesis of mitochondrial heme c and heme a in yeast and mammals." Biochim Biophys Acta 1659(2-3);153-9. PMID: 15576047

Obornik05: Obornik M, Green BR (2005). "Mosaic origin of the heme biosynthesis pathway in photosynthetic eukaryotes." Mol Biol Evol 22(12);2343-53. PMID: 16093570

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

Sato04: Sato S, Clough B, Coates L, Wilson RJ (2004). "Enzymes for heme biosynthesis are found in both the mitochondrion and plastid of the malaria parasite Plasmodium falciparum." Protist 155(1);117-25. PMID: 15144063

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

Wilson02: Wilson RJ (2002). "Progress with parasite plastids." J Mol Biol 319(2);257-74. PMID: 12051904

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

Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554

Alefounder88: Alefounder PR, Abell C, Battersby AR (1988). "The sequence of hemC, hemD and two additional E. coli genes." Nucleic Acids Res 16(20);9871. PMID: 3054815

Alwan89: Alwan AF, Mgbeje BI, Jordan PM (1989). "Purification and properties of uroporphyrinogen III synthase (co-synthase) from an overproducing recombinant strain of Escherichia coli K-12." Biochem J 264(2);397-402. PMID: 2557837

Anderson79: Anderson PM, Desnick RJ (1979). "Purification and properties of delta-aminolevulinate dehydrase from human erythrocytes." J Biol Chem 254(15);6924-30. PMID: 457661

Avissar89: Avissar YJ, Beale SI (1989). "Identification of the enzymatic basis for delta-aminolevulinic acid auxotrophy in a hemA mutant of Escherichia coli." J Bacteriol 171(6);2919-24. PMID: 2656630

Balg07: Balg C, Blais SP, Bernier S, Huot JL, Couture M, Lapointe J, Chenevert R (2007). "Synthesis of beta-ketophosphonate analogs of glutamyl and glutaminyl adenylate, and selective inhibition of the corresponding bacterial aminoacyl-tRNA synthetases." Bioorg Med Chem 15(1);295-304. PMID: 17049867

Banerjee04: Banerjee R, Dubois DY, Gauthier J, Lin SX, Roy S, Lapointe J (2004). "The zinc-binding site of a class I aminoacyl-tRNA synthetase is a SWIM domain that modulates amino acid binding via the tRNA acceptor arm." Eur J Biochem 271(4);724-33. PMID: 14764088

Battersby80: Battersby AR, Fookes CJ, Matcham GW, McDonald E (1980). "Biosynthesis of the pigments of life: formation of the macrocycle." Nature 285(5759);17-21. PMID: 6769048

Bernier05: Bernier S, Dubois DY, Habegger-Polomat C, Gagnon LP, Lapointe J, Chenevert R (2005). "Glutamylsulfamoyladenosine and pyroglutamylsulfamoyladenosine are competitive inhibitors of E. coli glutamyl-tRNA synthetase." J Enzyme Inhib Med Chem 20(1);61-7. PMID: 15895686

Bollivar04: Bollivar DW, Clauson C, Lighthall R, Forbes S, Kokona B, Fairman R, Kundrat L, Jaffe EK (2004). "Rhodobacter capsulatus porphobilinogen synthase, a high activity metal ion independent hexamer." BMC Biochem 5;17. PMID: 15555082

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

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.

Breton86: Breton R, Sanfacon H, Papayannopoulos I, Biemann K, Lapointe J (1986). "Glutamyl-tRNA synthetase of Escherichia coli. Isolation and primary structure of the gltX gene and homology with other aminoacyl-tRNA synthetases." J Biol Chem 261(23);10610-7. PMID: 3015933

Brun90: Brun YV, Sanfacon H, Breton R, Lapointe J (1990). "Closely spaced and divergent promoters for an aminoacyl-tRNA synthetase gene and a tRNA operon in Escherichia coli. Transcriptional and post-transcriptional regulation of gltX, valU and alaW." J Mol Biol 214(4);845-64. PMID: 2201777

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

Cao07: Cao J, Woodhall MR, Alvarez J, Cartron ML, Andrews SC (2007). "EfeUOB (YcdNOB) is a tripartite, acid-induced and CpxAR-regulated, low-pH Fe2+ transporter that is cryptic in Escherichia coli K-12 but functional in E. coli O157:H7." Mol Microbiol 65(4);857-75. PMID: 17627767

Cartron07: Cartron ML, Mitchell SA, Woodhall MR, Andrews SC, Watson KA (2007). "Preliminary X-ray diffraction analysis of YcdB from Escherichia coli: a novel haem-containing and Tat-secreted periplasmic protein with a potential role in iron transport." Acta Crystallogr Sect F Struct Biol Cryst Commun 63(Pt 1);37-41. PMID: 17183171

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

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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 Wed May 4, 2016, biocyc14.