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 → Tetrapyrrole Biosynthesis|
Some taxa known to possess this pathway include : Euglena gracilis , Homo sapiens , Plasmodium falciparum , Rhodobacter capsulatus , Rhodobacter sphaeroides , Saccharomyces cerevisiae , Streptomyces nodosus asukaensis
Tetrapyrrole compounds include four rings of the pyrrole type, generally linked together by single-atom bridges between the α positions of the five-membered pyrrole rings. Tetrapyrroles usually function as a metal-binding cofactor in many important enzymes, proteins and pigments, such as heme, chlorophyll, cobalamine (vitamin B12), siroheme, and cofator F430.
The tetrapyrrole biosynthetic pathway shown here beginning with glycine and succinyl-CoA (a TCA cycle intermediate) is found in animals, fungi, apicomplexan protozoa (such as the malaria parasite Plasmodium falciparum [Sato04]), and members of the α-proteobacteria. In other bacteria (including Escherichia coli) and archaea, tetrapyrrole biosynthesis begins with glutamate instead of glycine (see tetrapyrrole biosynthesis I (from glutamate)). Plants, who biosynthesize tetrapyrrole for use as heme and chlorophyll, also synthesize it from glutamate. Interestingly, the chloroplast-containing protozoan Euglena gracilis possesses both pathways.
Regardless whether the starting point is glycine or glutamate, both pathways converge at the intermediate 5-aminolevulinate and proceed through the important intermediate uroporphyrinogen-III, which is a major branch point that leads to biosynthesis of different tetrapyrrole compounds, such as the corrinoid cobalamine (vitamin B12) (see MetaCyc pathways adenosylcobalamin biosynthesis II (late cobalt incorporation) and adenosylcobalamin biosynthesis I (early cobalt insertion)), the methanogenic coenzyme F430 (see factor 430 biosynthesis), siroheme (see siroheme biosynthesis), and heme D.
This pathway has been studied in the photosynthetic purple nonsulfur α-proteobacterium Rhodobacter sphaeroides, which posesses two chromosomes and five additional replicons. In this organism there are two genes encoding 5-aminolevulinate synthase, hemA and hemT, that are present on chromosomes 1 and 2, respectively. Biosynthesis of the tetrapyrrole cofactors heme, bacteriochlorophyll a, siroheme and cob(I)alamin in this organism is highly regulated and is dependent upon expression of these two isozymes (in [ZeilstraRyalls95, Bolt99]).
Bolt99: Bolt EL, Kryszak L, Zeilstra-Ryalls J, Shoolingin-Jordan PM, Warren MJ (1999). "Characterization of the rhodobacter sphaeroides 5-aminolaevulinic acid synthase isoenzymes, HemA and HemT, isolated from recombinant Escherichia coli." Eur J Biochem 265(1);290-9. PMID: 10491185
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
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
Bishop90: Bishop DF (1990). "Two different genes encode delta-aminolevulinate synthase in humans: nucleotide sequences of cDNAs for the housekeeping and erythroid genes." Nucleic Acids Res 18(23);7187-8. PMID: 2263504
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
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
Chretien88: Chretien S, Dubart A, Beaupain D, Raich N, Grandchamp B, Rosa J, Goossens M, Romeo PH (1988). "Alternative transcription and splicing of the human porphobilinogen deaminase gene result either in tissue-specific or in housekeeping expression." Proc Natl Acad Sci U S A 85(1);6-10. PMID: 3422427
Cotter92a: Cotter PD, Willard HF, Gorski JL, Bishop DF (1992). "Assignment of human erythroid delta-aminolevulinate synthase (ALAS2) to a distal subregion of band Xp11.21 by PCR analysis of somatic cell hybrids containing X; autosome translocations." Genomics 13(1);211-2. PMID: 1577484
Cotter95: Cotter PD, Drabkin HA, Varkony T, Smith DI, Bishop DF (1995). "Assignment of the human housekeeping delta-aminolevulinate synthase gene (ALAS1) to chromosome band 3p21.1 by PCR analysis of somatic cell hybrids." Cytogenet Cell Genet 69(3-4);207-8. PMID: 7698013
Cox91: Cox TC, Bawden MJ, Martin A, May BK (1991). "Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron-responsive element in the mRNA." EMBO J 10(7);1891-902. PMID: 2050125
Deybach90: Deybach JC, de Verneuil H, Boulechfar S, Grandchamp B, Nordmann Y (1990). "Point mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria (Gunther's disease)." Blood 75(9);1763-5. PMID: 2331520
Evans86: Evans JN, Davies RC, Boyd AS, Ichinose I, Mackenzie NE, Scott AI, Baxter RL (1986). "Biosynthesis of porphyrins and corrins. 1. 1H and 13C NMR spectra of (hydroxymethyl)bilane and uroporphyrinogens I and III." Biochemistry 25(4);896-904. PMID: 3486001
Evans86a: Evans JN, Burton G, Fagerness PE, Mackenzie NE, Scott AI (1986). "Biosynthesis of porphyrins and corrins. 2. Isolation, purification, and NMR investigations of the porphobilinogen-deaminase covalent complex." Biochemistry 25(4);905-12. PMID: 3486002
Gill09: Gill R, Kolstoe SE, Mohammed F, Al D-Bass A, Mosely JE, Sarwar M, Cooper JB, Wood SP, Shoolingin-Jordan PM (2009). "Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria." Biochem J 420(1);17-25. PMID: 19207107
Grandchamp87: Grandchamp B, De Verneuil H, Beaumont C, Chretien S, Walter O, Nordmann Y (1987). "Tissue-specific expression of porphobilinogen deaminase. Two isoenzymes from a single gene." Eur J Biochem 162(1);105-10. PMID: 3816774
Hadener93: Hadener A, Matzinger PK, Malashkevich VN, Louie GV, Wood SP, Oliver P, Alefounder PR, Pitt AR, Abell C, Battersby AR (1993). "Purification, characterization, crystallisation and X-ray analysis of selenomethionine-labelled hydroxymethylbilane synthase from Escherichia coli." Eur J Biochem 211(3);615-24. PMID: 8436121
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