Abstract
Porphobilinogen is the monopyrrole precursor of all biological tetrapyrroles. The biosynthesis of porphobilinogen involves the asymmetric condensation of two molecules of 5-aminolevulinate and is carried out by the enzyme porphobilinogen synthase (PBGS), also known as 5-aminolevulinate dehydratase. This review documents what is known about the mechanism of the PBGS-catalyzed reaction. The metal ion constitutents of PBGS are of particular interest because PBGS is a primary target for the environmental toxin lead. Mammalian PBGS contains two zinc ions at each active site. Bacterial and plant PBGS use a third metal ion, magnesium, as an allosteric activator. In addition, some bacterial and plant PBGS may use magnesium in place of one or both of the zinc ions of mammalian PBGS. These phylogenetic variations in metal ion usage are described along with a proposed rationale for the evolutionary divergence in metal ion usage. Finally, I describe what is known about the structure of PBGS, an enzyme which has as yet eluded crystal structure determination.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Battle, A. M., and Stella, A. M. (1978).Int. J. Biochem. 9, 861–864.
Baum, S. J., and Plane, R. A. (1966).J. Am. Chem. Soc. 88, 910–913.
Beale, S. (1994). The sequence ofChlamydomonus PBGS, submitted to GenBank 1/95, Accession Number U19876.
Bevan, D. R., Bodlaender, P., and Shemin, D. (1980).J. Biol. Chem. 255, 2030–2035.
Bishop, T. R., Frelin, L. P., and Boyer, S. H. (1986).Nucleic Acids Res. 14, 0115.
Bishop, T. R., Hodes, Z. I., Frelin, L. P., and Boyer, S. H. (1989)Nucleic Acids Res. 17, 1775.
Bock, C., Katz, A., and Glusker, J. P. (1995).J. Am. Chem. Soc., in press.
Boese, Q. F., Spano, A. J., Li, J. M., and Timko, M. P. (1991).J. Biol. Chem. 266, 17060–17066.
Bröckl, G., Berchtold, M., Behr, M., and Konig, H. (1992)Gene 119, 151–152.
Chaudhry, A. G., and Jordan, P. M. (1976).Biochem. Soc. Trans. 4, 760–761.
Chauhan, S., and O'Brian, M. R. (1993).J. Bacteriol. 175, 7222–7227.
Christianson, D. W., and Lipscomb, W. N. (1986).Proc. Natl. Acad. Sci. USA 83, 7568–7572.
Clark, S. P. (1992).CABIOS 8, 535–583.
Dent, A. J., Beyersmann, D., Block, C., and Hasnain, S. S. (1990).Biochemistry 29, 7822–7828.
Echelard, Y., Dymetryszyn, J., Drolet, M., and Sasarman, A. (1988).Mol. Gen. Genet. 214, 503–508.
Evans, J. N. S., Fagerness, P. E., Mackenzie, N. E., and Scott, A. I. (1985).Magn. Reson. Chem. 23, 939–944.
Fabiano, E., and Goldin, B. T. (1991).J. Chem. Soc. Perkin Trans. 1, 3371–3375.
Fukuda, H., Paredes, S. R., and Batlle, A. M. (1988).Comp. Biochem. Physiol. B: Comp. Biochem. 91, 285–291.
Fukuda, H., Sopena de Kracoff, Y. E., Inigo, L. E., Paredes, S. R., Ferramola de Sancovich, A. M., Sancovich, H. A., and Batlle, A. M. (1990).J. Enzyme Inhib. 3, 295–302.
Gibbs, P. N., and Jordan, P. M. (1986).Biochem. J. 236, 447–451.
Gnonlonfoun, N., Filella, M., and Berthon, G. (1991).J. Inorg. Biochem. 42, 207–215.
Gribskov, M., and Devereux, J. (1991).Sequence Analysis Primer, Stockton Press, New York.
Guo, G. G., Gu, M., and Etlinger, J. D. (1994).J. Biol. Chem. 269, 12399–12402.
Gurba, P. E., Sennett, R. E., and Kobes, R. D. (1972).Arch. Biochem. Biophys. 150, 130–136.
Hampp, R., Kriebitzsch, C., and Ziegler, H. (1974).Naturwissenschaften 61, 504–505.
Hansson, M., Rutberg, L., Schroder, I., and Hederstedt, L. (1991).J. Bacteriol. 173, 2590–2599.
Hernberg, S., and Nikkanen, J. (1970).The Lancet, January 10, p. 63–64.
Hester, G., Brenner-Holzach, O., Rossi, F. A., Struck-Donatz, M., Winterhalter, K. H., Smit, J. D., and Piontek, K. (1991).FEBS Lett. 292, 237–242.
Indest, K., and Biel, A. J. (1994). Genbank Accession Number RCU14593.
Jaffe, E. K. (1993).Comments Inorg. Chem. 15, 67–93.
Jaffe, E. K., and Hanes, D. (1986).J. Biol. Chem. 261, 9348–9353.
Jaffe, E. K., and Markham, G. D. (1987). [published erratum appears inBiochemistry 26, 8030, 1987].Biochemistry 26, 4258–4264.
Jaffe, E. K., and Markham, G. D. (1988).Biochemistry 27, 4475–4481.
Jaffe, E. K., Salowe, S. P., Chen, N. T., and DeHaven, P. A. (1984).J. Biol. Chem. 259, 5032–5036.
Jaffe, E. K., Markham, G. D., and Rajagopalan, J. S. (1990).Biochemistry 29, 8345–8350.
Jaffe, E. K., Bagla, S., and Michini, P. A. (1991).Biol. Trace Element Res. 28, 223–231.
Jaffe, E. K., Abrams, W. R., Kaempfen, K. X., and Harris, K. A. (1992).Bioichemistry 31, 2113–2123.
Jaffe, E. K., Volin, M., Myers, C. B., and Abrams, W. R. (1994).Biochemistry 33, 11554–11562.
Jaffe, E. K., Ali, S., Mitchell, L. W., Taylor, K. M., Volin, M., and Markham, G. D. (1995).Biochemistry 34, 244–251.
Jones, M. C., Jenkins, J. M., Smith, A. G., and Howe, C. J. (1994).Plant Mol. Biol. 24, 435–448.
Jordan, P. (1990). InBiosynthesis of Heme and Chlorophylls (Dailey, H. A., ed.), McGraw-Hill, New York, pp. 55–121.
Jordan, P. M. (1991). InNew Comprehensive Biochemistry, Vol. 19 (Neuberger, A., and Van Deenan, L. L. M., eds.), Elsevier, Amsterdam.
Jordan, P. M., and Seehra, J. S. (1980).FEBS Lett. 114, 283–286.
Kaczor, C. M., Smith, M. W., Sangwan, I., and O'Brian, M. R. (1994).Plant Physiol. 104, 1411–1417.
Li, J. M., Russell, C. S., and Cosloy, S. D. (1989).Gene 75, 177–184.
Liedgens, W., Lutz, C., and Schneider, H. A. (1983).Eur. J. Biochem. 135, 75–79.
Lingner, B., and Kleinschmidt, T. (1983).Biosciences 38, 1059–1061.
Liu, J., Lin, S., Blochet, J. E., Pegolet, M., and Lapoint, J. (1993).Biochemistry 32, 11390–11396.
Maralihalli, G. B., Rao, S. R., and Bhagwat, A. S. (1985).Phytochemistry 24, 2533–2536.
Markham, G. D., Myers, C. B., Harris, K. A., Jr., Volin, M., and Jaffe, E. K. (1993).Protein Sci. 2, 71–79.
Masuoka, J., Hegenauer, J., Van Dyke, B. R., and Saltman, P. (1993).J. Biol. Chem. 268, 21533–21537.
Mitchell, L. W., Volin, M., and Jaffe, E. K. (1995)J. Biol. Chem., submitted for publication.
Mitchell, L. W., and Jaffe, E. K. (1993).Arch. Biochem. Biophys. 300, 169–177.
Myers, A. M., Crivellone, M. D., Koerner, T. J., and Tzagoloff, A. (1987).J. Biol. Chem. 262, 16822–16829.
Nandi, D. L. (1978).Biosciences 33, 799–802.
Nandi, D. L., and Shemin, D. (1968).J. Biol. Chem. 243, 1236–1242.
Neier, R. (1996). InAdvances in Nitrogen Heterocycles, Vol. 2 (Christopher, J. Moody, ed.), JAI Press, Greenwich, Connecticut.
Pilz, I., Schwarz, E., Vuga, M., and Beyersmann, D. (1988).Biol. Chem. Hoppe-Seyler 269, 1099–1103.
Polking, G. F., Hannapel, D. J., and Gladon, R. J. (1994). Submission to GenBank 3/94, Accession Number L31367.
Rost, B., and Sander, C. (1993).J. Mol. Biol. 232, 584–599.
Rost, B., and Sander, C. (1994).Proteins 19, 55–72.
Rost, B., Sander, C., and Schneider, R. (1994).CABIOS 10, 53–60.
Schaumburg, A., Schneider-Poetsch, H. J. A. W., and Eckerskom, C. (1992).Z. Naturforsch. Teil C J. Biosci. 47, 77–84.
Seehra, J. S., and Jordan, P. M. (1981).Eur. J. Biochem. 113, 435–446.
Shemin, D. (1972).The Enzymes, 3rd edn. (Boyer, P. D., ed.), Academic Press, New York, pp. 323–337.
Shemin, D. (1976).J. Biochem. 79, 37P-38P.
Shemin, D., and Russell, C. S. (1953).J. Am. Chem. Soc. 75, 4873.
Smith, A. G. (1988).Biochem. J. 249, 423–428.
Sollbach, M., and Schneider-Poetsch, H. J. A. W. (1993). Submission to GenBank 9/93, Accession Number X75043.
Spencer, P., and Jordan, P. M. (1993).Biochem. J. 290, 279–287.
Spencer, P., and Jordan, P. M. (1994).Biochem. J. 300, 373–381.
Tsukamoto, I., Yoshinaga, T., and Sano, S. (1975).Biochem. Biophys. Res. Commun. 67, 294–300.
Tsukamoto, I., Yoshinaga, T., and Sano, S. (1979).Biochim. Biophys. Acta 570, 167–178.
Walker, C. J., and Weinstein, J. D. (1994).Biochem. J. 299, 277–284.
Wetmur, J. G., Bishop, D. F., Cantelmo, C., and Desnick, R. J. (1986).Proc. Natl. Acad. Sci. USA 83, 7703–7707.
Wu, W. H., Shemin, D., Richards, K. E., and Williams, R. C. (1974).Proc. Natl. Acad. Sci. USA 71, 1767–1770.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jaffe, E.K. Porphobilinogen synthase, the first source of Heme's asymmetry. J Bioenerg Biomembr 27, 169–179 (1995). https://doi.org/10.1007/BF02110032
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02110032