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Ferrochelatase and N-alkylated porphyrins

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Summary

The final step in heme synthesis is catalyzed by the mitochondrial enzyme, ferrochelatase. Characterization of this enzyme has been complicated by a number of factors including the dependence of enzyme activity on lipids. Purification of ferrochelatase from rat and bovine sources has been achieved only relatively recently using blue Sepharose CL-6B chromatography. When 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) is given to animals, it produces a hepatic porphyria resembling human variegate porphyria thus providing an experimental system in which to study this disease. DDC has been found to cause the accumulation of a green pigment, identified as N-methyl protoporphyrin IX (N-MePP), which is a potent inhibitor of ferrochelatase. The source of the N-methyl substituent of N-MePP was found to be the 4-methyl group of DDC. Considerable evidence indicates that the protoporphyrin IX moiety of N-MePP originates from the heme moiety of cytochrome P-450 and that DDC is a suicide substrate for this hemoprotein. Some studies suggest that cytochrome P-450 isozymes differ in their susceptibility to destruction by DDC and its 4-alkyl analogues. Griseofulvin has also been reported to inhibit hepatic ferrochelatase in rodents but not in the 17-day old chick embryo nor in hepatocyte culture systems. Thus, the mechanism by which griseofulvin produces an experimental porphyria in chick embryo liver cell culture is different from that for rodents.

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References

  1. Jones OTG: In: Robbs DA, Pierpont WS (eds), Metals and Micronutrients. Academic Press, London, 1983, pp 125–146.

    Google Scholar 

  2. Porra RJ: Anal Biochem 68:289–298, 1975.

    Google Scholar 

  3. Jones OTG: Biochem J 107:113–119, 1968.

    Google Scholar 

  4. Little HN, Jones OTG: Biochem J 156:309–314, 1970.

    Google Scholar 

  5. Dailey HA: J Biol Chem 257:14714–14718, 1982.

    Google Scholar 

  6. Dailey HA: J Bacteriol 132:302–307, 1977.

    Google Scholar 

  7. Dailey HA, Lascelles J: Arch Biochem Biophys 160:523–529, 1974.

    Google Scholar 

  8. Jones MS, Jones OTG: Biochem J 119:453–462, 1970.

    Google Scholar 

  9. Porra RJ, Jones OTG: Biochem J 87:186–192, 1963.

    Google Scholar 

  10. Labbe RF, Hubbard N: Biochim Biophys Acta 41:185–191, 1960.

    Google Scholar 

  11. Kappas A, Sassa S, Anderson KE: In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds), The Metabolic Basis of Inherited Disease, 5th ed. McGraw-Hill, New York, 1982, pp 1301–1384.

    Google Scholar 

  12. Tschudy DP, Lamon JM: In: Bondy PK, Rosenberg LE (eds), Duncan's Diseases of Metabolism, 8th ed. Saunders, Philadelphia, 1980, p 939.

    Google Scholar 

  13. Brodie MJ, Moore MR, Goldberg A: Lancet 2:699–701, 1977.

    Google Scholar 

  14. Viljoen DJ, Cayanis E, Becker DM, Kramer S, Dawson B, Bernstein R: Am J Hematol 6:185–190, 1979.

    Google Scholar 

  15. Viljoen DJ, Cummins R, Alexopoulos J, Kramer S: Eur J Clin Invest 13:283–287, 1983.

    Google Scholar 

  16. Brenner DA, Bloomer JR: N Engl J Med 302:765–769, 1980.

    Google Scholar 

  17. Day RS, Blekkenhorst GH, Eales L: N Engl J Med 303: 1368–1369 (letter).

  18. Becker DM, ViLjoen JD, Katz J, Kramer S: Br J Haematol 36:171–179, 1977.

    Google Scholar 

  19. Marks GS: In: De Matteis F, Aldridge WN (eds), Handbook of Experimental Pharmacology, Vol 44. SpringerVerlag, Berlin, 1978, p 201.

    Google Scholar 

  20. De Matteis F: Enzyme 16:266–275, 1973.

    Google Scholar 

  21. De Matteis F: Pharmacol Rev 19:523–557, 1967.

    Google Scholar 

  22. Onisawa J, Labbe RF: J Biol Chem 238:724–727, 1963.

    Google Scholar 

  23. Tephly TR, Hasegawa E, Baron J: Metabol Clin Exp 20:200–214, 1971.

    Google Scholar 

  24. De Matteis F, Abbritti G, Gibbs AH: Biochem J 134:717–727, 1973.

    Google Scholar 

  25. Cole SPC, Vavasour EJ, Marks GS: Biochem Pharmacol 28:3533–3538, 1979.

    Google Scholar 

  26. Anderson KE: Biochim Biophys Acta 543:313–327, 1978.

    Google Scholar 

  27. Rifkind AB: J Biol Chem 254:4636–4644, 1979.

    Google Scholar 

  28. Cole SPC, Whitney RA, Marks GS: Mol Pharmacol 20:395–403, 1981.

    Google Scholar 

  29. Cole SPC, Massey TE, Marks GS, Racz WJ: Can J Physiol Pharmacol 59:1155–1158, 1981.

    Google Scholar 

  30. Mauzerall D, Granick S: J Biol Chem 232:1141–1162, 1958.

    Google Scholar 

  31. Heikel T, Lockwood WH, Rimington C: Nature 182:313, 1958.

    Google Scholar 

  32. Tokunaga R, Sano S: Biochem Biophys Res Commun 25:489–494, 1966.

    Google Scholar 

  33. Kassner RJ, Walchak H: Biochim Biophys Acta 304:294–303, 1973.

    Google Scholar 

  34. Taketani S, Tokunaga R: Eur J Biochem 127:443–447, 1982.

    Google Scholar 

  35. Bonkowsky HL, Bloomer JR, Ebert PS, Mahoney MJ: J Clin Invest 56:1139–1148, 1975.

    Google Scholar 

  36. Ruth GR, Schwartz S, Stephenson B: Science 198:199–201, 1977.

    Google Scholar 

  37. Jones MS, Jones OTG: Biochem J 113:507–514, 1969.

    CAS  PubMed  Google Scholar 

  38. MacKay R, Druyan R, Getz GS, Rabinowitz M: Biochem J 114:455–461, 1969.

    Google Scholar 

  39. Yoneyama Y, Tamai A, Yasuda T, Yoshikawa H: Biochim Biophys Acta 105:100–105, 1965.

    Google Scholar 

  40. Mazanowska A, Dancewicz AM, Malinowzka T, Kowalski E: Eur J Biochem 7:583–587, 1969.

    Google Scholar 

  41. Mailer K, Poulson R, Dolphin D, Hamilton AD: Biochem Biophys Res Commun 96:777–784, 1980.

    Google Scholar 

  42. Taketani S, Tokunaga R: J Biol Chem 256:12748–12753, 1981.

    Google Scholar 

  43. Dailey HA, Fleming JE: J Biol Chem 258:11453–11459, 1983.

    Google Scholar 

  44. Tanaka S, Nagahama S, Takeshita M, Yoneyama Y: J Biochem (Tokyo) 80:1067–1071, 1976.

    Google Scholar 

  45. Mazanowska AM, Neuberger A, Tait GH: Biochem J 98:117–127, 1966

    Google Scholar 

  46. Mazanowska A, Dancewicz AM: Acta Biochim Polonica 17:1–10, 1970.

    Google Scholar 

  47. Simpson DM, Poulson R: Biochim Biophys Acta 482:461–469, 1977.

    Google Scholar 

  48. Barnes R, Connelly JL, Jones OTG: Biochem J 128:1043–1055, 1972.

    Google Scholar 

  49. Koller ME, Romslo I, Flatmark T: Biochim Biophys Acta 449:480–490, 1976.

    Google Scholar 

  50. Labbe RF, Nielsen L: In: Doss M (ed), Porphyrins in Human Diseases. Karger, Basel, 1976, pp 141–147.

    Google Scholar 

  51. Vogeler WR, Mingioli ES: Clin Res 15:36, 1967 (abstract).

    Google Scholar 

  52. Labbe RF, Hubbard N: Biochim Biophys Acta 52:130–135, 1961.

    Google Scholar 

  53. Sinclair P, Gibbs AH, Sinclair JF, De Matteis F: Biochem J 178:529–538, 1979.

    Google Scholar 

  54. Labbe RF, Hubbard N, Caughey WS: Biochemistry 2:372–374, 1963.

    Google Scholar 

  55. Porra RJ, Jones OTG: Biochem J 87:186–192, 1963.

    Google Scholar 

  56. Honeybourne CL, Jackson JT, Jones OTG: FEBS Lett 98:207–210, 1979.

    Google Scholar 

  57. Jones MS, Jones OTG: Biochem Biophys Res Commun 41:1072–1079, 1970.

    Google Scholar 

  58. Koller ME, Romslo I: Biochim Biophys Acta 461:283–296, 1977.

    Google Scholar 

  59. Koller ME: FEBS Lett 100:47–51, 1979.

    Google Scholar 

  60. Moore MR: Int J Biochem 12:1089–1097, 1980.

    Google Scholar 

  61. Solomon HM, Figge FHJ: Proc Soc Exp Biol Med 100:583–586, 1959.

    Google Scholar 

  62. Figge FHJ: J Histochem Cytochem 7:257–261, 1959.

    Google Scholar 

  63. Tephly TR, Gibbs AH, De Matteis F: Biochem J 180:241–244, 1979.

    Google Scholar 

  64. De Matteis F, Gibbs AH, Jackson AH, Weerasinghe S: FEBS Lett 119:109–112, 1980.

    Google Scholar 

  65. Ortiz de Montellano PR, Beilan HS, Kunze KL: Proc Natl Acad Sci USA 78:1490–1494, 1981.

    Google Scholar 

  66. De Matteis F, Gibbs AH, Tephly TR: Biochem J 188:145–152, 1980.

    Google Scholar 

  67. Ortiz de Montellano PR, Kunze KL, Yost GS: Biochem Biophys Res Commun 83:132–137, 1978.

    Google Scholar 

  68. Ortiz de Montellano PR, Kunze KL: J Biol Chem 255:5578–5585, 1980.

    Google Scholar 

  69. Ortiz de Montellano PR, Mico BA: Mol Pharmacol 18:128–135, 1980.

    Google Scholar 

  70. Ortiz de Montellano PR, Kunze KL, Beilan HS, Wheeler C: Biochemistry 21:1331–1339, 1982.

    Google Scholar 

  71. Correia MA, Farrell GC, Olson S, Wong JS, Schmid R, Ortiz de Montellano PR, Beilan HS, Kunze KL, Mico BA: J Biol Chem 256:5466–5470, 1981.

    Google Scholar 

  72. De Matteis F, Cantoni L: Biochem J 183:99–103, 1979.

    Google Scholar 

  73. De Matteis F, Gibbs AH: Biochem J 187:285–288, 1980.

    Google Scholar 

  74. De Matteis F, Gibbs AH, Smith AG: Biochem J 189:645–648, 1980.

    Google Scholar 

  75. Ortiz de Montellano PR, Kunze KL, Cole SPC, Marks GS: Biochem Biophys Res Commun 97:1436–1442, 1980.

    Google Scholar 

  76. Ortiz de Montellano PR, Kunze KL, Cole SPC, Marks GS: Biochem Biophys Res Commun 103:581–586, 1981.

    Google Scholar 

  77. Cole SPC, Marks GS: Int J Biochem 12:989–992, 1980.

    Google Scholar 

  78. De Matteis F, Gibbs AH, Farmer PB, Lamb JH: FEBS Lett 129:328–331, 1981.

    Google Scholar 

  79. Tephly TR, Coffman BL, Ingall G, Abou Zeit-Har MS, Goff HM, Tabba HD, Smith KM: Arch Biochem Biophys 212:120–126, 1981.

    Google Scholar 

  80. Ortiz de Montellano PR, Beilan HS, Kunze KL: J Biol Chem 256:6708–6713, 1981.

    Google Scholar 

  81. Wada O, Yano Y, Urata G, Nakao K: Biochem Pharmacol 17:595–603, 1968.

    Google Scholar 

  82. Waterfield MD, Del Favero A, Gray CH: Biochim Biophys Acta 184:470–473, 1969.

    Google Scholar 

  83. Krupa V, Creighton JC, Freeman M, Marks GS: Can J Physiol Pharmacol 52:891–895, 1974.

    Google Scholar 

  84. Coffman BL, Ingall G, Tephly TR: Arch Biochem Biophys 218:220–224, 1982.

    Google Scholar 

  85. Augusto O, Beilan HS, Ortiz de Montellano PR: J Biol Chem 257:11288–11295, 1982.

    Google Scholar 

  86. Ortiz de Montellano PR, Correia MA: Ann Rev Pharmacol. Toxicol 23:481–503, 1983.

    Google Scholar 

  87. De Matteis F, Gibbs AH Hollands C: Biochem J 211:455–461, 1983.

    Google Scholar 

  88. Guengerich FP: Pharmac Ther 6:99–121, 1979.

    Google Scholar 

  89. Lu AYH: Drug Metab Rev 10:187–208, 1979.

    Google Scholar 

  90. Johnson EF: Rev Biochem Toxicol 1:1–26, 1979.

    Google Scholar 

  91. Sande MA, Mandell GL: In: Gilman AG, Goodman LS, Gilman A (eds), The Pharmacological Basis of Therapeutics, 6th ed. Macmillan, New York, 1980.

    Google Scholar 

  92. Barich LL, Schwartz J, Barich DJ, Horowitz MG: Antibiot Chemother 11:566–571, 1961.

    Google Scholar 

  93. Weston-Hurst E, Paget GE: Br J Dermatol 75:105–112, 1963.

    Google Scholar 

  94. De Matteis F, Rimington C: Br J Dermatol 75:91–104, 1963.

    Google Scholar 

  95. Poh-Fitzpatrick M, Lamola AA: J Clin Invest 60:380–389, 1977.

    Google Scholar 

  96. Poh-Fitzpatrick M, Sklar JA, Goldsman C, Lefkowitch JH: J Clin Invest 72:1449–1458, 1983.

    Google Scholar 

  97. Denk H, Kalt R, Abdelfattah-Gad M, Meyer UA: Cancer Res 41:1535–1538, 1981.

    Google Scholar 

  98. De Matteis F, Gibbs AH: Biochem J 146:285–287, 1975.

    Google Scholar 

  99. Cole SPC, Zelt DT, Marks GS: Mol Pharmacol 19:477–480, 1981.

    Google Scholar 

  100. Racz WJ, Marks GS: Biochem Pharmacol 18:2009–2018, 1969.

    Google Scholar 

  101. Granick S: J Biol Chem 241:1359–1375, 1966.

    Google Scholar 

  102. Cantoni L, Di Padova C, Rovagnati P, Ruggieri R, Dal Fiume D, Tritapepe R: Toxicology 27:27–39, 1983.

    Google Scholar 

  103. Shapiro SH, Wessely Z, Klavins JV: Ann Clin Lab Sci 10:45, 1980.

    Google Scholar 

  104. Chang RL, Symchowicz S, Lin C-C: Biochem Pharmacol 22:1389–1392, 1973.

    Google Scholar 

  105. Meyer UA, Strand LJ, Doss M, Rees AC, Marver HS: N Engl J Med 286:1277–1282, 1972.

    Google Scholar 

  106. Kushner JP, Barbuto AJ,Lee GR: J Clin Invest 58:1089–1097, 1976.

    Google Scholar 

  107. Elder GH, Lee GB, Tovey JA: N Engl J Med 299:274–278, 1978.

    CAS  PubMed  Google Scholar 

  108. Elder GH, Evans JO, Thomas N, Cox R, Brodie MJ, Moore MR, Goldberg A, Nicholson DC: Lancet 2:1217–1219, 1976.

    Google Scholar 

  109. Grandchamp B, Nordmann Y: Biochem Biophys Res Commun 74:1089–1095, 1977.

    Google Scholar 

  110. Brodie MJ, Thompson GG, Moore MR, Beattie AD, Goldberg A: Q J Med (New Series) 46:229–241, 1977.

    Google Scholar 

  111. Nordmann NY, Grandchamp B, Phang N, de Verneuil H, Grelier M, Noire J: Lancet 1:140, 1977.

    Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Queen's University, K7L 3N6, Kingston, Ontario, Canada

    Susan P. C. Cole

  2. Department of Pharmacology and Toxicology, Queen's University, K7L 3N6, Kingston, Ontario, Canada

    Gerald S. Marks

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  1. Susan P. C. Cole
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Cole, S.P.C., Marks, G.S. Ferrochelatase and N-alkylated porphyrins. Mol Cell Biochem 64, 127–137 (1984). https://doi.org/10.1007/BF00224769

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