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A primer on heme biosynthesis

  • Harry A. Dailey EMAIL logo und Amy E. Medlock ORCID logo EMAIL logo
Veröffentlicht/Copyright: 29. August 2022
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 403 Heft 11-12

Abstract

Heme (protoheme IX) is an essential cofactor for a large variety of proteins whose functions vary from one electron reactions to binding gases. While not ubiquitous, heme is found in the great majority of known life forms. Unlike most cofactors that are acquired from dietary sources, the vast majority of organisms that utilize heme possess a complete pathway to synthesize the compound. Indeed, dietary heme is most frequently utilized as an iron source and not as a source of heme. In Nature there are now known to exist three pathways to synthesize heme. These are the siroheme dependent (SHD) pathway which is the most ancient, but least common of the three; the coproporphyrin dependent (CPD) pathway which with one known exception is found only in gram positive bacteria; and the protoporphyrin dependent (PPD) pathway which is found in gram negative bacteria and all eukaryotes. All three pathways share a core set of enzymes to convert the first committed intermediate, 5-aminolevulinate (ALA) into uroporphyrinogen III. In the current review all three pathways are reviewed as well as the two known pathways to synthesize ALA. In addition, interesting features of some heme biosynthesis enzymes are discussed as are the regulation and disorders of heme biosynthesis.

Keywords: coproporphyrin dependent pathway; heme; mitochondrial heme metabolon; porphyria; protoporphyrin dependent pathway; siroheme dependent pathway
Corresponding authors: Harry A. Dailey, Department of Biochemistry and Molecular Biology, University of Georgia, Coverdell Center, N230, 500 D. W. Brooks Drive, Athens, GA 30602-1111, USA; and Department of Microbiology, University of Georgia, Athens, GA 30602-1111, USA, E-mail: ; and Amy E. Medlock, Department of Biochemistry and Molecular Biology, University of Georgia, Coverdell Center, N230, 500 D. W. Brooks Drive, Athens, GA 30602-1111, USA; and Augusta University/University of Georgia Medical Partnership, University of Georgia, Athens, GA, 30602, USA, E-mail:

Funding source: National Institute of Diabetes and Digestive and Kidney Diseases http://dx.doi.org/10.13039/100000062

Award Identifier / Grant number: DK110858

Award Identifier / Grant number: DK11653

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This research was funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease, grant number DK11653 and DK110858 via Pilot and Feasibility Grants from the University of Utah Center for Iron and Heme Disorders and Centers for Excellence in Hematology to A.E.M.

  3. Conflict of interest statement: The authors declare no conflict of interest.

References

Agostinis, P., Berg, K., Cengel, K.A., Foster, T.H., Girotti, A.W., Gollnick, S.O., Hahn, S.M., Hamblin, M.R., Juzeniene, A., Kessel, D., et al.. (2011). Photodynamic therapy of cancer: an update. Ca – Cancer J. Clin. 61: 250–281, https://doi.org/10.3322/caac.20114.Suche in Google Scholar PubMed PubMed Central

Al-Karadaghi, S., Hansson, M., Nikonov, S., Jonsson, B., and Hederstedt, L. (1997). Crystal structure of ferrochelatase: the terminal enzyme in heme biosynthesis. Structure 5: 1501–1510, https://doi.org/10.1016/s0969-2126(97)00299-2.Suche in Google Scholar PubMed

Astner, I., Schulze, J.O., van den Heuvel, J., Jahn, D., Schubert, W.D., and Heinz, D.W. (2005). Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans. EMBO J. 24: 3166–3177, https://doi.org/10.1038/sj.emboj.7600792.Suche in Google Scholar PubMed PubMed Central

Bai, Y., Kim, J.Y., Bisunke, B., Jayne, L.A., Silvaroli, J.A., Balzer, M.S., Gandhi, M., Huang, K.M., Sander, V., Prosek, J., et al.. (2021). Kidney toxicity of the BRAF-kinase inhibitor vemurafenib is driven by off-target ferrochelatase inhibition. Kidney Int. 100: 1214–1226, https://doi.org/10.1016/j.kint.2021.08.022.Suche in Google Scholar PubMed PubMed Central

Bailey, H.J., Bezerra, G.A., Marcero, J.R., Padhi, S., Foster, W.R., Rembeza, E., Roy, A., Bishop, D.F., Desnick, R.J., Bulusu, G., et al.. (2020). Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release. Nat. Commun. 11: 2813, https://doi.org/10.1038/s41467-020-16586-x.Suche in Google Scholar PubMed PubMed Central

Bairwa, G., Hee Jung, W., and Kronstad, J.W. (2017). Iron acquisition in fungal pathogens of humans. Metallomics 9: 215–227, https://doi.org/10.1039/c6mt00301j.Suche in Google Scholar PubMed PubMed Central

Bali, S., Lawrence, A.D., Lobo, S.A., Saraiva, L.M., Golding, B.T., Palmer, D.J., Howard, M.J., Ferguson, S.J., and Warren, M.J. (2011). Molecular hijacking of siroheme for the synthesis of heme and d1 heme. Proc. Natl. Acad. Sci. U.S.A. 108: 18260–18265, https://doi.org/10.1073/pnas.1108228108.Suche in Google Scholar PubMed PubMed Central

Beale, S.I. and Castelfranco, P.A. (1973). 14 C incorporation from exogenous compounds into -aminolevulinic acid by greening cucumber cotyledons. Biochem. Biophys. Res. Commun. 52: 143–149, https://doi.org/10.1016/0006-291x(73)90966-2.Suche in Google Scholar PubMed

Beale, S.I., Gough, S.P., and Granick, S. (1975). Biosynthesis of delta-aminolevulinic acid from the intact carbon skeleton of glutamic acid in greening barley. Proc. Natl. Acad. Sci. U.S.A. 72: 2719–2723, https://doi.org/10.1073/pnas.72.7.2719.Suche in Google Scholar PubMed PubMed Central

Bhasker, C.R., Burgiel, G., Neupert, B., Emery-Goodman, A., Kuhn, L.C., and May, B.K. (1993). The putative iron-responsive element in the human erythroid 5-aminolevulinate synthase mRNA mediates translational control. J. Biol. Chem. 268: 12699–12705, https://doi.org/10.1016/s0021-9258(18)31444-3.Suche in Google Scholar

Bishop, D.F., Henderson, A.S., and Astrin, K.H. (1990). Human delta-aminolevulinate synthase: assignment of the housekeeping gene to 3p21 and the erythroid-specific gene to the X chromosome. Genomics 7: 207–214, https://doi.org/10.1016/0888-7543(90)90542-3.Suche in Google Scholar PubMed

Bissell, D.M., Anderson, K.E., and Bonkovsky, H.L. (2017). Porphyria. N. Engl. J. Med. 377: 862–872, https://doi.org/10.1056/nejmra1608634.Suche in Google Scholar PubMed

Boynton, T.O., Daugherty, L.E., Dailey, T.A., and Dailey, H.A. (2009). Identification of Escherichia coli HemG as a novel, menadione-dependent flavodoxin with protoporphyrinogen oxidase activity. Biochemistry 48: 6705–6711, https://doi.org/10.1021/bi900850y.Suche in Google Scholar PubMed PubMed Central

Boynton, T.O., Gerdes, S., Craven, S.H., Neidle, E.L., Phillips, J.D., and Dailey, H.A. (2011). Discovery of a gene involved in a third bacterial protoporphyrinogen oxidase activity through comparative genomic analysis and functional complementation. Appl. Environ. Microbiol. 77: 4795–4801, https://doi.org/10.1128/aem.00171-11.Suche in Google Scholar

Breinig, S., Kervinen, J., Stith, L., Wasson, A.S., Fairman, R., Wlodawer, A., Zdanov, A., and Jaffe, E.K. (2003). Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase. Nat. Struct. Biol. 10: 757–763, https://doi.org/10.1038/nsb963.Suche in Google Scholar PubMed

Brown, B.L., Kardon, J.R., Sauer, R.T., and Baker, T.A. (2018). Structure of the mitochondrial aminolevulinic acid synthase, a key heme biosynthetic enzyme. Structure 26: 580–589.e4, https://doi.org/10.1016/j.str.2018.02.012.Suche in Google Scholar PubMed PubMed Central

Bryant, D.A., Hunter, C.N., and Warren, M.J. (2020). Biosynthesis of the modified tetrapyrroles-the pigments of life. J. Biol. Chem. 295: 6888–6925, https://doi.org/10.1074/jbc.rev120.006194.Suche in Google Scholar

Brzezowski, P., Richter, A.S., and Grimm, B. (2015). Regulation and function of tetrapyrrole biosynthesis in plants and algae. Biochim. Biophys. Acta 1847: 968–985, https://doi.org/10.1016/j.bbabio.2015.05.007.Suche in Google Scholar PubMed

Burch, J.S., Marcero, J.R., Maschek, J.A., Cox, J.E., Jackson, L.K., Medlock, A.E., Phillips, J.D., and Dailey, H.A.Jr. (2018). Glutamine via alpha-ketoglutarate dehydrogenase provides succinyl-CoA for heme synthesis during erythropoiesis. Blood 132: 987–998, https://doi.org/10.1182/blood-2018-01-829036.Suche in Google Scholar PubMed PubMed Central

Campanini, B., Bettati, S., Di Salvo, M.L., Mozzarelli, A., and Contestabile, R. (2013). Asymmetry of the active site loop conformation between subunits of glutamate-1-semialdehyde aminomutase in solution. BioMed Res. Int. 2013: 353270.10.1155/2013/353270Suche in Google Scholar PubMed PubMed Central

Choby, J.E. and Skaar, E.P. (2019). Staphylococcus aureus coproporphyrinogen III oxidase is required for aerobic and anaerobic heme synthesis. mSphere 4: e00235–19, doi:https://doi.org/10.1128/msphere.00235-19.Suche in Google Scholar PubMed PubMed Central

Chung, J., Chen, C., and Paw, B.H. (2012). Heme metabolism and erythropoiesis. Curr. Opin. Hematol. 19: 156–162, https://doi.org/10.1097/moh.0b013e328351c48b.Suche in Google Scholar

Coates, L., Beaven, G., Erskine, P.T., Beale, S.I., Wood, S.P., Shoolingin-Jordan, P.M., and Cooper, J.B. (2005). Structure of Chlorobium vibrioforme 5-aminolaevulinic acid dehydratase complexed with a diacid inhibitor. Acta Crystallogr. Sect. D Biol. Crystallogr. 61: 1594–1598, https://doi.org/10.1107/s0907444905030350.Suche in Google Scholar PubMed

Corradi, H.R., Corrigall, A.V., Boix, E., Mohan, C.G., Sturrock, E.D., Meissner, P.N., and Acharya, K.R. (2006). Crystal structure of protoporphyrinogen oxidase from Myxococcus xanthus and its complex with the inhibitor acifluorfen. J. Biol. Chem. 281: 38625–38633, https://doi.org/10.1074/jbc.m606640200.Suche in Google Scholar PubMed PubMed Central

Corrigall, A.V., Siziba, K.B., Maneli, M.H., Shephard, E.G., Ziman, M., Dailey, T.A., Dailey, H.A., Kirsch, R.E., and Meissner, P.N. (1998). Purification of and kinetic studies on a cloned protoporphyrinogen oxidase from the aerobic bacterium Bacillus subtilis. Arch. Biochem. Biophys. 358: 251–256, https://doi.org/10.1006/abbi.1998.0834.Suche in Google Scholar PubMed

Cox, T.C., Bawden, M.J., Abraham, N.G., Bottomley, S.S., May, B.K., Baker, E., Chen, L.Z., and Sutherland, G.R. (1990). Erythroid 5-aminolevulinate synthase is located on the X chromosome. Am. J. Hum. Genet. 46: 107–111.Suche in Google Scholar

Crane, B.R. and Getzoff, E.D. (1996). The relationship between structure and function for the sulfite reductases. Curr. Opin. Struct. Biol. 6: 744–756, https://doi.org/10.1016/s0959-440x(96)80003-0.Suche in Google Scholar PubMed

Crooks, D.R., Ghosh, M.C., Haller, R.G., Tong, W.H., and Rouault, T.A. (2010). Posttranslational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery. Blood 115: 860–869, https://doi.org/10.1182/blood-2009-09-243105.Suche in Google Scholar PubMed PubMed Central

Czarnecki, O. and Grimm, B. (2012). Post-translational control of tetrapyrrole biosynthesis in plants, algae, and cyanobacteria. J. Exp. Bot. 63: 1675–1687, https://doi.org/10.1093/jxb/err437.Suche in Google Scholar PubMed

Dailey, H.A. (1990). Conversion of coproporphyrinogen to protoheme in higher eukaryotes and bacteria: terminal three enzymes. In: Dailey, H.A. (Ed.), Biosynthesis of heme and chlorophylls. McGraw-Hill Publishing Company, New York, NY.Suche in Google Scholar

Dailey, H.A. and Dailey, T.A. (1996a). Protoporphyrinogen oxidase of Myxococcus xanthus. Expression, purification, and characterization of the cloned enzyme. J. Biol. Chem. 271: 8714–8718, https://doi.org/10.1074/jbc.271.15.8714.Suche in Google Scholar PubMed

Dailey, H.A. and Dailey, T.A. (2003). Ferrochelatase. In: Kadish, K.M., Smith, K.M., and Guilard, R. (Eds.), The porphyrin handbook. Academic Press, San Diego, CA.Suche in Google Scholar

Dailey, H.A., Dailey, T.A., Gerdes, S., Jahn, D., Jahn, M., O’Brian, M.R., and Warren, M.J. (2017). Prokaryotic heme biosynthesis: multiple pathways to a common essential product. Microbiol. Mol. Biol. Rev. 81: e00048–16, doi:https://doi.org/10.1128/mmbr.00048-16.Suche in Google Scholar

Dailey, H.A. and Gerdes, S. (2015). HemQ: an iron-coproporphyrin oxidative decarboxylase for protoheme synthesis in Firmicutes and Actinobacteria. Arch. Biochem. Biophys. 574: 27–35, https://doi.org/10.1016/j.abb.2015.02.017.Suche in Google Scholar PubMed PubMed Central

Dailey, H.A., Gerdes, S., Dailey, T.A., Burch, J.S., and Phillips, J.D. (2015). Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin. Proc. Natl. Acad. Sci. U.S.A. 112: 2210–2215, https://doi.org/10.1073/pnas.1416285112.Suche in Google Scholar PubMed PubMed Central

Dailey, H.A. and Meissner, P.N. (2013). Erythroid heme biosynthesis and its disorders. Cold Spring Harb. Perspect. Med. 3: a011676, https://doi.org/10.1101/cshperspect.a011676.Suche in Google Scholar PubMed PubMed Central

Dailey, H.A. and Smith, A. (1984). Differential interaction of porphyrins used in photoradiation therapy with ferrochelatase. Biochem. J. 223: 441–445, https://doi.org/10.1042/bj2230441.Suche in Google Scholar PubMed PubMed Central

Dailey, T.A., Boynton, T.O., Albetel, A.N., Gerdes, S., Johnson, M.K., and Dailey, H.A. (2010). Discovery and Characterization of HemQ: an essential heme biosynthetic pathway component. J. Biol. Chem. 285: 25978–25986, https://doi.org/10.1074/jbc.m110.142604.Suche in Google Scholar

Dailey, T.A. and Dailey, H.A. (1996b). Human protoporphyrinogen oxidase: expression, purification, and characterization of the cloned enzyme. Protein Sci. 5: 98–105, https://doi.org/10.1002/pro.5560050112.Suche in Google Scholar PubMed PubMed Central

Dailey, T.A. and Dailey, H.A. (2002). Identification of [2Fe-2S] clusters in microbial ferrochelatases. J. Bacteriol. 184: 2460–2464, https://doi.org/10.1128/jb.184.9.2460-2464.2002.Suche in Google Scholar

Dailey, T.A., Meissner, P., and Dailey, H.A. (1994). Expression of a cloned protoporphyrinogen oxidase. J. Biol. Chem. 269: 813–815, https://doi.org/10.1016/s0021-9258(17)42182-x.Suche in Google Scholar

Dietz, J.V., Willoughby, M.M., Piel, R.B.3rd, Ross, T.A., Bohovych, I., Addis, H.G., Fox, J.L., Lanzilotta, W.N., Dailey, H.A., Wohlschlegel, J.A., et al.. (2021). Mitochondrial contact site and cristae organizing system (MICOS) machinery supports heme biosynthesis by enabling optimal performance of ferrochelatase. Redox Biol. 46: 102125, https://doi.org/10.1016/j.redox.2021.102125.Suche in Google Scholar PubMed PubMed Central

Dolmans, D.E., Fukumura, D., and Jain, R.K. (2003). Photodynamic therapy for cancer. Nat. Rev. Cancer 3: 380–387, https://doi.org/10.1038/nrc1071.Suche in Google Scholar PubMed

Ducamp, S. and Fleming, M.D. (2019). The molecular genetics of sideroblastic anemia. Blood 133: 59–69, https://doi.org/10.1182/blood-2018-08-815951.Suche in Google Scholar PubMed PubMed Central

Dutt, S., Hamza, I., and Bartnikas, T.B. (2022). Molecular mechanisms of iron and heme metabolism. Annu. Rev. Nutr. 42: 7.1–7.25, doi:https://doi.org/10.1146/annurev-nutr-062320-112625.Suche in Google Scholar PubMed PubMed Central

Eldridge, M.G. and Dailey, H.A. (1992). Yeast ferrochelatase: expression in a baculovirus system and purification of the expression protein. Protein Sci. 1: 271–277, https://doi.org/10.1002/pro.5560010209.Suche in Google Scholar PubMed PubMed Central

Erskine, P.T., Newbold, R., Roper, J., Coker, A., Warren, M.J., Shoolingin-Jordan, P.M., Wood, S.P., and Cooper, J.B. (1999a). The Schiff base complex of yeast 5-aminolaevulinic acid dehydratase with laevulinic acid. Protein Sci. 8: 1250–1256, https://doi.org/10.1110/ps.8.6.1250.Suche in Google Scholar PubMed PubMed Central

Erskine, P.T., Norton, E., Cooper, J.B., Lambert, R., Coker, A., Lewis, G., Spencer, P., SARWAR, M., Wood, S.P., Warren, M.J., et al.. (1999b). X-ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli complexed with the inhibitor levulinic acid at 2.0 A resolution. Biochemistry 38: 4266–4276, https://doi.org/10.1021/bi982137w.Suche in Google Scholar PubMed

Espinas, N.A., Kobayashi, K., Sato, Y., Mochizuki, N., Takahashi, K., Tanaka, R., and Masuda, T. (2016). Allocation of heme is differentially regulated by ferrochelatase isoforms in Arabidopsis cells. Front. Plant Sci. 7: 1326, https://doi.org/10.3389/fpls.2016.01326.Suche in Google Scholar PubMed PubMed Central

Fernandez-Murray, J.P., Prykhozhij, S.V., Dufay, J.N., Steele, S.L., Gaston, D., Nasrallah, G.K., Coombs, A.J., Liwski, R.S., Fernandez, C.V., Berman, J.N., et al.. (2016). Glycine and folate ameliorate models of congenital sideroblastic anemia. PLoS Genet. 12: e1005783, https://doi.org/10.1371/journal.pgen.1005783.Suche in Google Scholar PubMed PubMed Central

Ferreira, G.C. (2013). Heme synthesis. In: Lennarz, W. and Lane, M. (Eds.), Encyclopedia of biological chemistry, 2nd ed. Elsevier, London, UK, pp. 539–542.10.1016/B978-0-12-378630-2.00145-6Suche in Google Scholar

Ferreira, G.C., Andrew, T.L., Karr, S.W., and Dailey, H.A. (1988). Organization of the terminal two enzymes of the heme biosynthetic pathway. Orientation of protoporphyrinogen oxidase and evidence for a membrane complex. J. Biol. Chem. 263: 3835–3839, https://doi.org/10.1016/s0021-9258(18)69000-3.Suche in Google Scholar

Ferreira, G.C. and Dailey, H.A. (1988). Mouse protoporphyrinogen oxidase. Kinetic parameters and demonstration of inhibition by bilirubin. Biochem. J. 250: 597–603, https://doi.org/10.1042/bj2500597.Suche in Google Scholar PubMed PubMed Central

Finnigan, J.D., Young, C., Cook, D.J., Charnock, S.J., and Black, G.W. (2020). Cytochromes P450 (P450s): a review of the class system with a focus on prokaryotic P450s. Adv. Protein Chem. Struct. Biol. 122: 289–320.10.1016/bs.apcsb.2020.06.005Suche in Google Scholar PubMed

Frankenberg, N., Erskine, P.T., Cooper, J.B., Shoolingin-Jordan, P.M., Jahn, D., and Heinz, D.W. (1999). High resolution crystal structure of a Mg2+-dependent porphobilinogen synthase. J. Mol. Biol. 289: 591–602, https://doi.org/10.1006/jmbi.1999.2808.Suche in Google Scholar PubMed

Freeman, S.L., Kwon, H., Portolano, N., Parkin, G., Venkatraman Girija, U., Basran, J., Fielding, A.J., Fairall, L., Svistunenko, D.A., Moody, P.C.E., et al.. (2019). Heme binding to human CLOCK affects interactions with the E-box. Proc. Natl. Acad. Sci. U.S.A. 116: 19911–19916, https://doi.org/10.1073/pnas.1905216116.Suche in Google Scholar PubMed PubMed Central

Fujiwara, T. and Harigae, H. (2015). Biology of heme in mammalian erythroid cells and related disorders. BioMed Res. Int. 2015: 278536, https://doi.org/10.1155/2015/278536.Suche in Google Scholar PubMed PubMed Central

Fukuhara, H., Inoue, K., Kurabayashi, A., Furihata, M., Fujita, H., Utsumi, K., Sasaki, J., and Shuin, T. (2013). The inhibition of ferrochelatase enhances 5-aminolevulinic acid-based photodynamic action for prostate cancer. Photodiagnosis Photodyn. Ther. 10: 399–409, https://doi.org/10.1016/j.pdpdt.2013.03.003.Suche in Google Scholar PubMed

Galmozzi, A., Kok, B.P., Kim, A.S., Montenegro-Burke, J.R., Lee, J.Y., Spreafico, R., Mosure, S., Albert, V., Cintron-Colon, R., Godio, C., et al.. (2019). PGRMC2 is an intracellular haem chaperone critical for adipocyte function. Nature 576: 138–142, https://doi.org/10.1038/s41586-019-1774-2.Suche in Google Scholar PubMed PubMed Central

Garcia-Santos, D., Schranzhofer, M., Bergeron, R., Sheftel, A.D., and Ponka, P. (2017). Extracellular glycine is necessary for optimal hemoglobinization of erythroid cells. Haematologica 102: 1314–1323, https://doi.org/10.3324/haematol.2016.155671.Suche in Google Scholar PubMed PubMed Central

Ge, H., Lv, X., Fan, J., Gao, Y., Teng, M., and Niu, L. (2010). Crystal structure of glutamate-1-semialdehyde aminotransferase from Bacillus subtilis with bound pyridoxamine-5’-phosphate. Biochem. Biophys. Res. Commun. 402: 356–360, https://doi.org/10.1016/j.bbrc.2010.10.033.Suche in Google Scholar PubMed

Grandchamp, B., Phung, N., and Nordmann, Y. (1978). The mitochondrial localization of coproporphyrinogen III oxidase. Biochem. J. 176: 97–102, https://doi.org/10.1042/bj1760097.Suche in Google Scholar PubMed PubMed Central

Hamza, I. and Dailey, H.A. (2012). One ring to rule them all: trafficking of heme and heme synthesis intermediates in the metazoans. Biochim. Biophys. Acta 1823: 1617–1632, https://doi.org/10.1016/j.bbamcr.2012.04.009.Suche in Google Scholar PubMed PubMed Central

Hansson, M. and Hederstedt, L. (1994). Bacillus subtilis HemY is a peripheral membrane protein essential for protoheme IX synthesis which can oxidize coproporphyrinogen III and protoporphyrinogen IX. J. Bacteriol. 176: 5962–5970, https://doi.org/10.1128/jb.176.19.5962-5970.1994.Suche in Google Scholar PubMed PubMed Central

Hansson, M.D., Karlberg, T., Rahardja, M.A., Al-Karadaghi, S., and Hansson, M. (2007). Amino acid residues His183 and Glu264 in Bacillus subtilis ferrochelatase direct and facilitate the insertion of metal ion into protoporphyrin IX. Biochemistry 46: 87–94, https://doi.org/10.1021/bi061760a.Suche in Google Scholar PubMed

Hansson, M.D., Karlberg, T., Soderberg, C.A., Rajan, S., Warren, M.J., Al-Karadaghi, S., Rigby, S.E., and Hansson, M. (2011). Bacterial ferrochelatase turns human: Tyr13 determines the apparent metal specificity of Bacillus subtilis ferrochelatase. J. Biol. Inorg. Chem. 16: 235–242, https://doi.org/10.1007/s00775-010-0720-4.Suche in Google Scholar PubMed

Harbin, B.M. and Dailey, H.A. (1985). Orientation of ferrochelatase in bovine liver mitochondria. Biochemistry 24: 366–370, https://doi.org/10.1021/bi00323a019.Suche in Google Scholar PubMed

Hennig, M., Grimm, B., Contestabile, R., John, R.A., and Jansonius, J.N. (1997). Crystal structure of glutamate-1-semialdehyde aminomutase: an alpha2-dimeric vitamin B6-dependent enzyme with asymmetry in structure and active site reactivity. Proc. Natl. Acad. Sci. U.S.A. 94: 4866–4871, https://doi.org/10.1073/pnas.94.10.4866.Suche in Google Scholar PubMed PubMed Central

Hobbs, C., Dailey, H.A., and Shepherd, M. (2016). The HemQ coprohaem decarboxylase generates reactive oxygen species: implications for the evolution of classical haem biosynthesis. Biochem. J. 473: 3997–4009, https://doi.org/10.1042/bcj20160696.Suche in Google Scholar

Hofbauer, S., Helm, J., Obinger, C., Djinovic-Carugo, K., and Furtmuller, P.G. (2020). Crystal structures and calorimetry reveal catalytically relevant binding mode of coproporphyrin and coproheme in coproporphyrin ferrochelatase. FEBS J. 287: 2779–2796, https://doi.org/10.1111/febs.15164.Suche in Google Scholar PubMed PubMed Central

Hofbauer, S., Howes, B.D., Flego, N., Pirker, K.F., Schaffner, I., Mlynek, G., Djinovic-Carugo, K., Furtmuller, P.G., Smulevich, G., and Obinger, C. (2016a). From chlorite dismutase towards HemQ – the role of the proximal H-bonding network in haeme binding. Biosci. Rep. 36: e00312, https://doi.org/10.1042/bsr20150330.Suche in Google Scholar

Hofbauer, S., Mlynek, G., Milazzo, L., Puhringer, D., Maresch, D., Schaffner, I., Furtmuller, P.G., Smulevich, G., Djinovic-Carugo, K., and Obinger, C. (2016b). Hydrogen peroxide-mediated conversion of coproheme to heme b by HemQ-lessons from the first crystal structure and kinetic studies. FEBS J. 283: 4386–4401, https://doi.org/10.1111/febs.13930.Suche in Google Scholar PubMed PubMed Central

Hoggins, M., Dailey, H.A., Hunter, C.N., and Reid, J.D. (2007). Direct measurement of metal ion chelation in the active site of human ferrochelatase. Biochemistry 46: 8121–8127, https://doi.org/10.1021/bi602418e.Suche in Google Scholar PubMed PubMed Central

Homedan, C., Laafi, J., Schmitt, C., Gueguen, N., Lefebvre, T., Karim, Z., Desquiret-Dumas, V., Wetterwald, C., Deybach, J.C., Gouya, L., et al.. (2014). Acute intermittent porphyria causes hepatic mitochondrial energetic failure in a mouse model. Int. J. Biochem. Cell Biol. 51: 93–101, https://doi.org/10.1016/j.biocel.2014.03.032.Suche in Google Scholar PubMed

Huang, W. and Wilks, A. (2017). Extracellular heme uptake and the challenge of bacterial cell membranes. Annu. Rev. Biochem. 86: 799–823, https://doi.org/10.1146/annurev-biochem-060815-014214.Suche in Google Scholar PubMed

Jackson, A.H., Elder, G.H., and Smith, S.G. (1978). The metabolism of coproporphyrinogen-III into protoporphyrin-IX. Int. J. Biochem. 9: 877–882, https://doi.org/10.1016/0020-711x(78)90063-0.Suche in Google Scholar PubMed

Jaffe, E.K. (2000). The porphobilinogen synthase family of metalloenzymes. Acta Crystallogr. Sect. D Biol. Crystallogr. 56: 115–128, https://doi.org/10.1107/s0907444999014894.Suche in Google Scholar PubMed

Jaffe, E.K. (2016). The remarkable character of porphobilinogen synthase. Acc. Chem. Res. 49: 2509–2517, https://doi.org/10.1021/acs.accounts.6b00414.Suche in Google Scholar PubMed PubMed Central

Jordan, P.M. (1991). The biosynthesis of 5-aminolaevulinic acid and its transformation into uroporphyrinogen III. In: Jordan, P.M. (Ed.), New comprehensive biochemistry, Vol. 19. Elsevier, London, pp. 1–66.10.1016/S0167-7306(08)60108-8Suche in Google Scholar

Jordan, P.M. and Warren, M.J. (1987). Evidence for a dipyrromethane cofactor at the catalytic site of E. coli porphobilinogen deaminase. FEBS Lett. 225: 87–92, https://doi.org/10.1016/0014-5793(87)81136-5.Suche in Google Scholar PubMed

Karlberg, T., Hansson, M.D., Yengo, R.K., Johansson, R., Thorvaldsen, H.O., Ferreira, G.C., Hansson, M., and Al-Karadaghi, S. (2008). Porphyrin binding and distortion and substrate specificity in the ferrochelatase reaction: the role of active site residues. J. Mol. Biol. 378: 1074–1083, https://doi.org/10.1016/j.jmb.2008.03.040.Suche in Google Scholar PubMed PubMed Central

Kato, K., Tanaka, R., Sano, S., Tanaka, A., and 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: 16649–16654, https://doi.org/10.1073/pnas.1000771107.Suche in Google Scholar PubMed PubMed Central

Kelly, S.L. and Kelly, D.E. (2013). Microbial cytochromes P450: biodiversity and biotechnology. Where do cytochromes P450 come from, what do they do and what can they do for us? Philos. Trans. R. Soc. Lond. B Biol. Sci. 368: 20120476, https://doi.org/10.1098/rstb.2012.0476.Suche in Google Scholar PubMed PubMed Central

Kikuchi, G., Kumar, A., Talmage, P., and Shemin, D. (1958). The enzymatic synthesis of delta-aminolevulinic acid. J. Biol. Chem. 233: 1214–1219, https://doi.org/10.1016/s0021-9258(19)77371-2.Suche in Google Scholar

Klaeger, S., Gohlke, B., Perrin, J., Gupta, V., Heinzlmeir, S., Helm, D., Qiao, H., Bergamini, G., Handa, H., Savitski, M.M., et al.. (2016). Chemical proteomics reveals ferrochelatase as a common off-target of kinase inhibitors. ACS Chem. Biol. 11: 1245–1254, https://doi.org/10.1021/acschembio.5b01063.Suche in Google Scholar PubMed

Koch, M., Breithaupt, C., Kiefersauer, R., Freigang, J., Huber, R., and Messerschmidt, A. (2004). Crystal structure of protoporphyrinogen IX oxidase: a key enzyme in haem and chlorophyll biosynthesis. EMBO J. 23: 1720–1728, https://doi.org/10.1038/sj.emboj.7600189.Suche in Google Scholar PubMed PubMed Central

Kresge, N., Simoni, R.D., and Hill, R.L. (2006). A pathway for heme biosynthesis: the work of David Shemin. J. Biol. Chem. 281, https://doi.org/10.1016/s0021-9258(18)95190-2.Suche in Google Scholar

Kuhner, M., Haufschildt, K., Neumann, A., Storbeck, S., Streif, J., and Layer, G. (2014). The alternative route to heme in the methanogenic archaeon Methanosarcina barkeri. Archaea 2014: 327637, https://doi.org/10.1155/2014/327637.Suche in Google Scholar PubMed PubMed Central

Lanzilotta, W.N. and Dailey, H.A. (2007). Human ferrochelatase. In: Messerschmidt, A. (Ed.), Handbook of metalloproteins. John Wiley & Sons, Chichester, UK.10.1002/0470028637.met215Suche in Google Scholar

Lascelles, J. (1964). Tetrapyrrole Biosynthesis and its regulation. W. A. Benjamin, Inc, New York, NY.Suche in Google Scholar

Layer, G. (2021). Heme biosynthesis in prokaryotes. Biochim. Biophys. Acta Mol. Cell Res. 1868: 118861, https://doi.org/10.1016/j.bbamcr.2020.118861.Suche in Google Scholar PubMed

Layer, G., Moser, J., Heinz, D.W., Jahn, D., and Schubert, W.D. (2003). Crystal structure of coproporphyrinogen III oxidase reveals cofactor geometry of radical SAM enzymes. EMBO J. 22: 6214–6224, https://doi.org/10.1093/emboj/cdg598.Suche in Google Scholar PubMed PubMed Central

Layer, G., Reichelt, J., Jahn, D., and Heinz, D.W. (2010). Structure and function of enzymes in heme biosynthesis. Protein Sci. 19: 1137–1161, https://doi.org/10.1002/pro.405.Suche in Google Scholar PubMed PubMed Central

Lecerof, D., Fodje, M., Hansson, A., Hansson, M., and Al-Karadaghi, S. (2000). Structural and mechanistic basis of porphyrin metallation by ferrochelatase. J. Mol. Biol. 297: 221–232, https://doi.org/10.1006/jmbi.2000.3569.Suche in Google Scholar PubMed

Lecerof, D., Fodje, M.N., Alvarez Leon, R., Olsson, U., Hansson, A., Sigfridsson, E., Ryde, U., Hansson, M., and Al-Karadaghi, S. (2003). Metal binding to Bacillus subtilis ferrochelatase and interaction between metal sites. J. Biol. Inorg. Chem. 8: 452–458, https://doi.org/10.1007/s00775-002-0436-1.Suche in Google Scholar PubMed

Lee, D.S., Flachsova, E., Bodnarova, M., Demeler, B., Martasek, P., and Raman, C.S. (2005). Structural basis of hereditary coproporphyria. Proc. Natl. Acad. Sci. U.S.A. 102: 14232–14237, https://doi.org/10.1073/pnas.0506557102.Suche in Google Scholar PubMed PubMed Central

Liu, G., Sil, D., Maio, N., Tong, W.H., Bollinger, J.M.Jr., Krebs, C., and Rouault, T.A. (2020). Heme biosynthesis depends on previously unrecognized acquisition of iron-sulfur cofactors in human amino-levulinic acid dehydratase. Nat. Commun. 11: 6310, https://doi.org/10.1038/s41467-020-20145-9.Suche in Google Scholar PubMed PubMed Central

Lobo, S.A., Brindley, A., Warren, M.J., and Saraiva, L.M. (2009). Functional characterization of the early steps of tetrapyrrole biosynthesis and modification in Desulfovibrio vulgaris Hildenborough. Biochem. J. 420: 317–325, https://doi.org/10.1042/bj20090151.Suche in Google Scholar PubMed

Lobo, S.A., Scott, A., VIDEIRA, M.A., Winpenny, D., Gardner, M., Palmer, M.J., Schroeder, S., Lawrence, A.D., Parkinson, T., Warren, M.J., et al.. (2015). Staphylococcus aureus haem biosynthesis: characterisation of the enzymes involved in final steps of the pathway. Mol. Microbiol. 97: 472–487, https://doi.org/10.1111/mmi.13041.Suche in Google Scholar PubMed

Luer, C., Schauer, S., Mobius, K., Schulze, J., Schubert, W.D., Heinz, D.W., Jahn, D., and Moser, J. (2005). Complex formation between glutamyl-tRNA reductase and glutamate-1-semialdehyde 2, 1-aminomutase in Escherichia coli during the initial reactions of porphyrin biosynthesis. J. Biol. Chem. 280: 18568–18572, https://doi.org/10.1074/jbc.m500440200.Suche in Google Scholar

Luer, C., Schauer, S., Virus, S., Schubert, W.D., Heinz, D.W., Moser, J., and Jahn, D. (2007). Glutamate recognition and hydride transfer by Escherichia coli glutamyl-tRNA reductase. FEBS J. 274: 4609–4614, https://doi.org/10.1111/j.1742-4658.2007.05989.x.Suche in Google Scholar PubMed

Maio, N., Zhang, D.L., Ghosh, M.C., Jain, A., Santamaria, A.M., and Rouault, T.A. (2021). Mechanisms of cellular iron sensing, regulation of erythropoiesis and mitochondrial iron utilization. Semin. Hematol. 58: 161–174, https://doi.org/10.1053/j.seminhematol.2021.06.001.Suche in Google Scholar PubMed PubMed Central

Marcero, J.R., Cox, J.E., Bergonia, H.A., Medlock, A.E., Phillips, J.D., and Dailey, H.A. (2021). The immunometabolite itaconate inhibits heme synthesis and remodels cellular metabolism in erythroid precursors. Blood Adv. 5: 4831–4841, https://doi.org/10.1182/bloodadvances.2021004750.Suche in Google Scholar PubMed PubMed Central

Masoumi, A., Heinemann, I.U., Rohde, M., Koch, M., Jahn, M., and Jahn, D. (2008). Complex formation between protoporphyrinogen IX oxidase and ferrochelatase during haem biosynthesis in Thermosynechococcus elongatus. Microbiology (Read.) 154: 3707–3714, https://doi.org/10.1099/mic.0.2008/018705-0.Suche in Google Scholar PubMed

Matringe, M., Camadro, J.M., Labbe, P., and Scalla, R. (1989). Protoporphyrinogen oxidase as a molecular target for diphenyl ether herbicides. Biochem. J. 260: 231–235, https://doi.org/10.1042/bj2600231.Suche in Google Scholar PubMed PubMed Central

Medlock, A., Swartz, L., Dailey, T.A., Dailey, H.A., and Lanzilotta, W.N. (2007). Substrate interactions with human ferrochelatase. Proc. Natl. Acad. Sci. U.S.A. 104: 1789–1793, https://doi.org/10.1073/pnas.0606144104.Suche in Google Scholar PubMed PubMed Central

Medlock, A.E. and Dailey, H.A. (1996). Human coproporphyrinogen oxidase is not a metalloprotein. J. Biol. Chem. 271: 32507–32510, https://doi.org/10.1074/jbc.271.51.32507.Suche in Google Scholar PubMed

Medlock, A.E. and Dailey, H.A. (2000). Examination of the activity of carboxyl-terminal chimeric constructs of human and yeast ferrochelatases. Biochemistry 39: 7461–7467, https://doi.org/10.1021/bi000134p.Suche in Google Scholar PubMed

Medlock, A.E. and Dailey, H.A. (2009). Regulation of mammalian heme biosynthesis. In: Warren, M.J. and Smith, A.G. (Eds.), Tetrapyrroles: birth, lift and death. Landes Bioscience Springer Science+Business Media, New York, NY, pp. 116–127.10.1007/978-0-387-78518-9_7Suche in Google Scholar

Medlock, A.E., Hixon, J.C., Bhuiyan, T., and Cobine, P.A. (2022). Prime real estate: metals, cofactors and MICOS. Front. Cell Dev. Biol. 10: 892325, doi:https://doi.org/10.3389/fcell.2022.892325.Suche in Google Scholar PubMed PubMed Central

Medlock, A.E., Shiferaw, M.T., Marcero, J.R., Vashisht, A.A., Wohlschlegel, J.A., Phillips, J.D., and Dailey, H.A. (2015). Identification of the mitochondrial heme metabolism complex. PLoS One 10: e0135896, https://doi.org/10.1371/journal.pone.0135896.Suche in Google Scholar PubMed PubMed Central

Melefors, O., Goossen, B., Johansson, H.E., Stripecke, R., Gray, N.K., and Hentze, M.W. (1993). Translational control of 5-aminolevulinate synthase mRNA by iron-responsive elements in erythroid cells. J. Biol. Chem. 268: 5974–5978, https://doi.org/10.1016/s0021-9258(18)53414-1.Suche in Google Scholar

Mobius, K., Arias-Cartin, R., Breckau, D., Hannig, A.L., Riedmann, K., Biedendieck, R., Schroder, S., Becher, D., Magalon, A., Moser, J., et al.. (2010). Heme biosynthesis is coupled to electron transport chains for energy generation. Proc. Natl. Acad. Sci. U.S.A. 107: 10436–10441, https://doi.org/10.1073/pnas.1000956107.Suche in Google Scholar PubMed PubMed Central

Moser, J., Lorenz, S., Hubschwerlen, C., Rompf, A., and Jahn, D. (1999). Methanopyrus kandleri glutamyl-tRNA reductase. J. Biol. Chem. 274: 30679–30685, https://doi.org/10.1074/jbc.274.43.30679.Suche in Google Scholar PubMed

Moser, J., Schubert, W.D., Beier, V., Bringemeier, I., Jahn, D., and Heinz, D.W. (2001). V-shaped structure of glutamyl-tRNA reductase, the first enzyme of tRNA-dependent tetrapyrrole biosynthesis. EMBO J. 20: 6583–6590, https://doi.org/10.1093/emboj/20.23.6583.Suche in Google Scholar PubMed PubMed Central

Moulin, M. and Smith, A.G. (2005). Regulation of tetrapyrrole biosynthesis in higher plants. Biochem. Soc. Trans. 33: 737–742, https://doi.org/10.1042/bst0330737.Suche in Google Scholar PubMed

Muckenthaler, M.U., Rivella, S., Hentze, M.W., and Galy, B. (2017). A red carpet for iron metabolism. Cell 168: 344–361, https://doi.org/10.1016/j.cell.2016.12.034.Suche in Google Scholar PubMed PubMed Central

Munro, A.W., Girvan, H.M., Mclean, K.J., Cheesman, M.R., and Leys, D. (2009). Heme and hemoproteins. In: Warren, M.J., and Smith, A.G. (Eds.), Tetrapyrroles: birth, life and death. Landes Bioscience and Springer Science+Business Media, New York, NY.10.1007/978-0-387-78518-9_10Suche in Google Scholar

Muschalek, W., Hermasch, M.A., Poblete-Gutierrez, P., and Frank, J. (2022). The porphyrias. JDDG J. der Deutschen Dermatol. Gesellschaft 20: 316–331, https://doi.org/10.1111/ddg.14743.Suche in Google Scholar PubMed

Nemeth, E., Valore, E.V., Territo, M., Schiller, G., Lichtenstein, A., and Ganz, T. (2003). Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 101: 2461–2463, https://doi.org/10.1182/blood-2002-10-3235.Suche in Google Scholar PubMed

Nogaj, L.A. and Beale, S.I. (2005). Physical and kinetic interactions between glutamyl-tRNA reductase and glutamate-1-semialdehyde aminotransferase of Chlamydomonas reinhardtii. J. Biol. Chem. 280: 24301–24307, https://doi.org/10.1074/jbc.m502483200.Suche in Google Scholar PubMed

Obi, C.D., Bhuiyan, T., Dailey, H.A., and Medlock, A.E. (2022). Ferrochelatase: mapping the intersection of iron and porphyrin metabolism in the mitochondria. Front. Cell Dev. Biol. 10: 894591, doi:https://doi.org/10.3389/fcell.2022.894591.Suche in Google Scholar PubMed PubMed Central

Olsson, U., Billberg, A., Sjovall, S., Al-Karadaghi, S., and Hansson, M. (2002). In vivo and in vitro studies of Bacillus subtilis ferrochelatase mutants suggest substrate channeling in the heme biosynthesis pathway. J. Bacteriol. 184: 4018–4024, https://doi.org/10.1128/jb.184.14.4018-4024.2002.Suche in Google Scholar

Pagani, A., Nai, A., Silvestri, L., and Camaschella, C. (2019). Hepcidin and anemia: a tight relationship. Front. Physiol. 10: 1294, https://doi.org/10.3389/fphys.2019.01294.Suche in Google Scholar PubMed PubMed Central

Pazdernik, M., Mares, J., Pilny, J., and Sobotka, R. (2019). The antenna-like domain of the cyanobacterial ferrochelatase can bind chlorophyll and carotenoids in an energy-dissipative configuration. J. Biol. Chem. 294: 11131–11143, https://doi.org/10.1074/jbc.ra119.008434.Suche in Google Scholar

Pfanzagl, V., Holcik, L., Maresch, D., Gorgone, G., Michlits, H., Furtmuller, P.G., and Hofbauer, S. (2018). Coproheme decarboxylases – phylogenetic prediction versus biochemical experiments. Arch. Biochem. Biophys. 640: 27–36, https://doi.org/10.1016/j.abb.2018.01.005.Suche in Google Scholar PubMed PubMed Central

Phillips, J.D. (2019). Heme biosynthesis and the porphyrias. Mol. Genet. Metabol. 128: 164–177, https://doi.org/10.1016/j.ymgme.2019.04.008.Suche in Google Scholar PubMed PubMed Central

Phillips, J.D., Warby, C.A., Whitby, F.G., Kushner, J.P., and Hill, C.P. (2009). Substrate shuttling between active sites of uroporphyrinogen decarboxylase is not required to generate coproporphyrinogen. J. Mol. Biol. 389: 306–314, https://doi.org/10.1016/j.jmb.2009.04.013.Suche in Google Scholar PubMed PubMed Central

Piel, R.B.3rd, Dailey, H.A.Jr., and Medlock, A.E. (2019). The mitochondrial heme metabolon: insights into the complex(ity) of heme synthesis and distribution. Mol. Genet. Metabol. 128: 198–203, https://doi.org/10.1016/j.ymgme.2019.01.006.Suche in Google Scholar PubMed PubMed Central

Piel, R.B.3rd, Shiferaw, M.T., Vashisht, A.A., Marcero, J.R., Praissman, J.L., Phillips, J.D., Wohlschlegel, J.A., and Medlock, A.E. (2016). A novel role for progesterone receptor membrane component 1 (PGRMC1): a partner and regulator of ferrochelatase. Biochemistry 55: 5204–5217, https://doi.org/10.1021/acs.biochem.6b00756.Suche in Google Scholar PubMed PubMed Central

Poli, A., Schmitt, C., Moulouel, B., Mirmiran, A., Puy, H., Lefebvre, T., and Gouya, L. (2021). Iron, heme synthesis and erythropoietic porphyrias: a complex interplay. Metabolites 11: 798, doi:https://doi.org/10.3390/metabo11120798.Suche in Google Scholar PubMed PubMed Central

Proulx, K.L., Woodard, S.I., and Dailey, H.A. (1993). In situ conversion of coproporphyrinogen to heme by murine mitochondria: terminal steps of the heme biosynthetic pathway. Protein Sci. 2: 1092–1098, https://doi.org/10.1002/pro.5560020703.Suche in Google Scholar PubMed PubMed Central

Puy, H., Gouya, L., and Deybach, J.C. (2010). Porphyrias. Lancet 375: 924–937, https://doi.org/10.1016/s0140-6736(09)61925-5.Suche in Google Scholar PubMed

Qin, X., Tan, Y., Wang, L., Wang, Z., Wang, B., Wen, X., Yang, G., Xi, Z., and Shen, Y. (2011). Structural insight into human variegate porphyria disease. FASEB J. 25: 653–664, https://doi.org/10.1096/fj.10-170811.Suche in Google Scholar PubMed

Rhee, H.W., Zou, P., Udeshi, N.D., Martell, J.D., Mootha, V.K., Carr, S.A., and Ting, A.Y. (2013). Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging. Science 339: 1328–1331, https://doi.org/10.1126/science.1230593.Suche in Google Scholar PubMed PubMed Central

Richter, A.S., Banse, C., and Grimm, B. (2019). The GluTR-binding protein is the heme-binding factor for feedback control of glutamyl-tRNA reductase. Elife 8, https://doi.org/10.7554/elife.46300.Suche in Google Scholar PubMed PubMed Central

Roberts, G.P., Kerby, R.L., Youn, H., and Conrad, M. (2005). CooA, a paradigm for gas sensing regulatory proteins. J. Inorg. Biochem. 99: 280–292, https://doi.org/10.1016/j.jinorgbio.2004.10.032.Suche in Google Scholar PubMed

Schauer, S., Chaturvedi, S., Randau, L., Moser, J., Kitabatake, M., Lorenz, S., Verkamp, E., Schubert, W.D., Nakayashiki, T., Murai, M., et al.. (2002). Escherichia coli glutamyl-tRNA reductase. Trapping the thioester intermediate. J. Biol. Chem. 277: 48657–48663, https://doi.org/10.1074/jbc.m206924200.Suche in Google Scholar

Schranzhofer, M., Schifrer, M., Cabrera, J.A., Kopp, S., Chiba, P., Beug, H., and Mullner, E.W. (2006). Remodeling the regulation of iron metabolism during erythroid differentiation to ensure efficient heme biosynthesis. Blood 107: 4159–4167, https://doi.org/10.1182/blood-2005-05-1809.Suche in Google Scholar PubMed

Schubert, H.L., Phillips, J.D., Heroux, A., and Hill, C.P. (2008). Structure and mechanistic implications of a uroporphyrinogen III synthase-product complex. Biochemistry 47: 8648–8655, https://doi.org/10.1021/bi800635y.Suche in Google Scholar PubMed PubMed Central

Schulze, J.O., Schubert, W.D., Moser, J., Jahn, D., and Heinz, D.W. (2006). Evolutionary relationship between initial enzymes of tetrapyrrole biosynthesis. J. Mol. Biol. 358: 1212–1220, https://doi.org/10.1016/j.jmb.2006.02.064.Suche in Google Scholar PubMed

Sebastiani, F., Michlits, H., Lier, B., Becucci, M., Furtmuller, P.G., Oostenbrink, C., Obinger, C., Hofbauer, S., and Smulevich, G. (2021). Reaction intermediate rotation during the decarboxylation of coproheme to heme b in C. diphtheriae. Biophys. J. 120: 4903, https://doi.org/10.1016/j.bpj.2021.10.002.Suche in Google Scholar PubMed PubMed Central

Sellers, V.M., Johnson, M.K., and Dailey, H.A. (1996). Function of the [2FE-2S] cluster in mammalian ferrochelatase: a possible role as a nitric oxide sensor. Biochemistry 35: 2699–2704, https://doi.org/10.1021/bi952631p.Suche in Google Scholar PubMed

Sevalkar, R.R., Glasgow, J.N., Pettinati, M., Marti, M.A., Reddy, V.P., Basu, S., Alipour, E., Kim-Shapiro, D.B., Estrin, D.A., Lancaster, J.R.Jr., et al.. (2022). Mycobacterium tuberculosis DosS binds H2S through its Fe3+ heme iron to regulate the DosR dormancy regulon. Redox Biol. 52: 102316, https://doi.org/10.1016/j.redox.2022.102316.Suche in Google Scholar PubMed PubMed Central

Shah, D.I., Takahashi-Makise, N., Cooney, J.D., Li, L., Schultz, I.J., Pierce, E.L., Narla, A., Seguin, A., Hattangadi, S.M., Medlock, A.E., et al.. (2012). Mitochondrial Atpif1 regulates haem synthesis in developing erythroblasts. Nature 491: 608–612, https://doi.org/10.1038/nature11536.Suche in Google Scholar PubMed PubMed Central

Shemin, D. and Rittenberg, D. (1945). The utilization of glycine for the synthesis of a porphyrin. J. Biol. Chem. 159: 567–568, https://doi.org/10.1016/s0021-9258(19)52819-8.Suche in Google Scholar

Shepherd, M., Dailey, T.A., and Dailey, H.A. (2006). A new class of [2Fe-2S]-cluster-containing protoporphyrin (IX) ferrochelatases. Biochem. J. 397: 47–52, https://doi.org/10.1042/bj20051967.Suche in Google Scholar PubMed PubMed Central

Shipovskov, S., Karlberg, T., Fodje, M., Hansson, M.D., Ferreira, G.C., Hansson, M., Reimann, C.T., and Al-Karadaghi, S. (2005). Metallation of the transition-state inhibitor N-methyl mesoporphyrin by ferrochelatase: implications for the catalytic reaction mechanism. J. Mol. Biol. 352: 1081–1090, https://doi.org/10.1016/j.jmb.2005.08.002.Suche in Google Scholar PubMed

Shoolingin-Jordan, P.M., Al-Dbass, A., Mcneill, L.A., Sarwar, M., and Butler, D. (2003). Human porphobilinogen deaminase mutations in the investigation of the mechanism of dipyrromethane cofactor assembly and tetrapyrrole formation. Biochem. Soc. Trans. 31: 731–735, https://doi.org/10.1042/bst0310731.Suche in Google Scholar PubMed

Sibata, C.H., Colussi, V.C., Oleinick, N.L., and Kinsella, T.J. (2001). Photodynamic therapy in oncology. Expet Opin. Pharmacother. 2: 917–927, https://doi.org/10.1517/14656566.2.6.917.Suche in Google Scholar PubMed

Stark, W.M., Baker, M.G., Raithby, P.R., Leeper, F.J., and Battersby, A.R. (1985). The spiro intermediate proposed for biosynthesis of the natural porphyrins – synthesis and properties of its macrocycle. J. Chem. Soc., Chem. Commun.: 1294–1296, https://doi.org/10.1039/c39850001294.Suche in Google Scholar

Storbeck, S., Rolfes, S., Raux-Deery, E., Warren, M.J., Jahn, D., and Layer, G. (2010). A novel pathway for the biosynthesis of heme in Archaea: genome-based bioinformatic predictions and experimental evidence. Archaea 2010: 175050, https://doi.org/10.1155/2010/175050.Suche in Google Scholar PubMed PubMed Central

Suh, Y., Gandhi, J., Seyam, O., Jiang, W., Joshi, G., Smith, N.L., and Ali Khan, S. (2019). Neurological and neuropsychiatric manifestations of porphyria. Int. J. Neurosci. 129: 1226–1233, https://doi.org/10.1080/00207454.2019.1655014.Suche in Google Scholar PubMed

Sutherland, G.R., Baker, E., Callen, D.F., Hyland, V.J., May, B.K., Bawden, M.J., Healy, H.M., and Borthwick, I.A. (1988). 5-Aminolevulinate synthase is at 3p21 and thus not the primary defect in X-linked sideroblastic anemia. Am. J. Hum. Genet. 43: 331–335.Suche in Google Scholar

Weerth, R.S., Medlock, A.E., and Dailey, H.A. (2021). Ironing out the distribution of [2Fe-2S] motifs in ferrochelatases. J. Biol. Chem. 297: 101017, https://doi.org/10.1016/j.jbc.2021.101017.Suche in Google Scholar PubMed PubMed Central

Wilks, A. and Heinzl, G. (2014). Heme oxygenation and the widening paradigm of heme degradation. Arch. Biochem. Biophys. 544: 87–95, https://doi.org/10.1016/j.abb.2013.10.013.Suche in Google Scholar PubMed PubMed Central

Wu, C.K., Dailey, H.A., Rose, J.P., Burden, A., Sellers, V.M., and Wang, B.C. (2001). The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis. Nat. Struct. Biol. 8: 156–160, https://doi.org/10.1038/84152.Suche in Google Scholar PubMed

Xiao, S.H. and Sun, J. (2017). Schistosoma hemozoin and its possible roles. Int. J. Parasitol. 47: 171–183, https://doi.org/10.1016/j.ijpara.2016.10.005.Suche in Google Scholar PubMed

Yasuda, M., Chen, B., and Desnick, R.J. (2019). Recent advances on porphyria genetics: inheritance, penetrance and molecular heterogeneity, including new modifying/causative genes. Mol. Genet. Metabol. 128: 320–331, https://doi.org/10.1016/j.ymgme.2018.11.012.Suche in Google Scholar PubMed PubMed Central

Yien, Y.Y., Robledo, R.F., Schultz, I.J., Takahashi-Makise, N., Gwynn, B., Bauer, D.E., Dass, A., Yi, G., Li, L., Hildick-Smith, G.J., et al.. (2014). TMEM14C is required for erythroid mitochondrial heme metabolism. J. Clin. Invest. 124: 4294–4304, https://doi.org/10.1172/jci76979.Suche in Google Scholar

Zappa, S., Li, K., and Bauer, C.E. (2010). The tetrapyrrole biosynthetic pathway and its regulation in Rhodobacter capsulatus. Adv. Exp. Med. Biol. 675: 229–250.10.1007/978-1-4419-1528-3_13Suche in Google Scholar PubMed PubMed Central

Zhang, T., Chen, J., Zheng, P., Gong, W., Sun, J., and Liu, H. (2022). Crystal structure of 5-Aminolevulinate synthase HemA from Rhodopseudomonas palustris presents multiple conformations. Biochem. Biophys. Res. Commun. 609: 100–104, https://doi.org/10.1016/j.bbrc.2022.04.021.Suche in Google Scholar PubMed

Zhao, A., Fang, Y., Chen, X., Zhao, S., Dong, W., LIN, Y., Gong, W., and Liu, L. (2014). Crystal structure of Arabidopsis glutamyl-tRNA reductase in complex with its stimulator protein. Proc. Natl. Acad. Sci. U.S.A. 111: 6630–6635, https://doi.org/10.1073/pnas.1400166111.Suche in Google Scholar PubMed PubMed Central

Received: 2022-06-14
Accepted: 2022-08-05
Published Online: 2022-08-29
Published in Print: 2022-11-25

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Heme research – the past, the present and the future
  3. A primer on heme biosynthesis
  4. New roles for GAPDH, Hsp90, and NO in regulating heme allocation and hemeprotein function in mammals
  5. The role of host heme in bacterial infection
  6. Signal transduction mechanisms in heme-based globin-coupled oxygen sensors with a focus on a histidine kinase (AfGcHK) and a diguanylate cyclase (YddV or EcDosC)
  7. Heme delivery to heme oxygenase-2 involves glyceraldehyde-3-phosphate dehydrogenase
  8. Novel insights into heme binding to hemoglobin
  9. Extracellular hemin is a reverse use-dependent gating modifier of cardiac voltage-gated Na+ channels
  10. Assessment of the breadth of binding promiscuity of heme towards human proteins
  11. Determination of free heme in stored red blood cells with an apo-horseradish peroxidase-based assay
  12. Comparative studies of soluble and immobilized Fe(III) heme-peptide complexes as alternative heterogeneous biocatalysts
https://doi.org/10.1515/hsz-2022-0205
Schlagwörter für diesen Artikel
coproporphyrin dependent pathway; heme; mitochondrial heme metabolon; porphyria; protoporphyrin dependent pathway; siroheme dependent pathway

Artikel in diesem Heft

  1. Frontmatter
  2. Heme research – the past, the present and the future
  3. A primer on heme biosynthesis
  4. New roles for GAPDH, Hsp90, and NO in regulating heme allocation and hemeprotein function in mammals
  5. The role of host heme in bacterial infection
  6. Signal transduction mechanisms in heme-based globin-coupled oxygen sensors with a focus on a histidine kinase (AfGcHK) and a diguanylate cyclase (YddV or EcDosC)
  7. Heme delivery to heme oxygenase-2 involves glyceraldehyde-3-phosphate dehydrogenase
  8. Novel insights into heme binding to hemoglobin
  9. Extracellular hemin is a reverse use-dependent gating modifier of cardiac voltage-gated Na+ channels
  10. Assessment of the breadth of binding promiscuity of heme towards human proteins
  11. Determination of free heme in stored red blood cells with an apo-horseradish peroxidase-based assay
  12. Comparative studies of soluble and immobilized Fe(III) heme-peptide complexes as alternative heterogeneous biocatalysts
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