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MetaCyc Pathway: tetrapyrrole biosynthesis II (from glycine)
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: tetrapyrrole biosynthesis II (from glycine)

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 BiosynthesisTetrapyrrole Biosynthesis

Some taxa known to possess this pathway include : Euglena gracilis, Homo sapiens, Plasmodium falciparum, Rhodobacter capsulatus, Rhodobacter sphaeroides, Saccharomyces cerevisiae, Streptomyces nodosus asukaensis

Expected Taxonomic Range: Alveolata, Euglenozoa, Fungi, Metazoa, Proteobacteria, Streptomyces

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 (aerobic) and adenosylcobalamin biosynthesis I (anaerobic)), 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]).

Superpathways: superpathway of heme biosynthesis from glycine, superpathway of bacteriochlorophyll a biosynthesis

Variants: tetrapyrrole biosynthesis I (from glutamate)

Created 15-May-2006 by Caspi R, SRI International


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

Heinemann08: Heinemann IU, Jahn M, Jahn D (2008). "The biochemistry of heme biosynthesis." Arch Biochem Biophys 474(2);238-51. PMID: 18314007

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

ZeilstraRyalls95: Zeilstra-Ryalls JH, Kaplan S (1995). "Aerobic and anaerobic regulation in Rhodobacter sphaeroides 2.4.1: the role of the fnrL gene." J Bacteriol 177(22);6422-31. PMID: 7592416

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

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

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

Bawden87: Bawden MJ, Borthwick IA, Healy HM, Morris CP, May BK, Elliott WH (1987). "Sequence of human 5-aminolevulinate synthase cDNA." Nucleic Acids Res 15(20);8563. PMID: 3671094

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

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

Burnham63: Burnham B. F., Lascelles J. (1963). "Control of porphyrin biosynthesis through a negative-feedback mechanism." Biochem. J. 87, 462-472.

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

Cotter92: 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

Ferreira95: Ferreira GC, Gong J (1995). "5-Aminolevulinate synthase and the first step of heme biosynthesis." J Bioenerg Biomembr 27(2);151-9. PMID: 7592562

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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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.