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:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Porphyrin Compounds Biosynthesis → Heme 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
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 [Sato04a]), 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, Wilson02a, 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 (late cobalt incorporation)), 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.
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
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
Sato04a: 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
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
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
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
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
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
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
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
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
Curnow98: Curnow AW, Tumbula DL, Pelaschier JT, Min B, Soll D (1998). "Glutamyl-tRNA(Gln) amidotransferase in Deinococcus radiodurans may be confined to asparagine biosynthesis." Proc Natl Acad Sci U S A 95(22);12838-43. PMID: 9789001
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