Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1977 May;74(5):2118–2120. doi: 10.1073/pnas.74.5.2118

Postulated deficiency of hepatic heme and repair by hematin infusions in the "inducible" hepatic porphyrias.

C J Watson, C A Pierach, I Bossenmaier, R Cardinal
PMCID: PMC431086  PMID: 266732

Abstract

There is compelling, indirect evidence of hepatic heme deficiency due primarily to the respective genetic errors of the three inducible hepatic porphyrias, acute intermittent porphyria, porphyria variegata, and hereditary coproporphyria. The induction is enhanced by exogenous inducers such as barbiturate, estrogens and other "porphyrogenic" chemicals and factors, including glucose deprivation. The newer knowledge of the induction of delta-aminolevulinic acid synthetase [delta-aminolevulinate synthase; succinyl--CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37] in relation to inadequate heme, and repression by heme, stimulated early trials of hematin infusions to overcome the acute relapse in the foregoing inducible porphyrias. Recently this experience has been considerably expanded, 143 infusions of hematin having been given in 22 cases. Studies of the effect on the serum concentrations of delta-aminolevulinic acid and porphobilinogen have shown a highly significant decline, often to 0, especially of delta-aminolevulinic acid. A distinct relationship to the clinical severity of the attack has been evident in the frequency and magnitude of decline of serum delta-aminolevulinic acid and porphobilinogen. This was regularly associated with objective clinical improvement.

Full text

PDF
2118

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ACKNER B., COOPER J. E., GRAY C. H., KELLY M. Acute porphyria: a neuropsychiatric and biochemical study. J Psychosom Res. 1962 Jan-Mar;6:1–24. doi: 10.1016/0022-3999(62)90019-3. [DOI] [PubMed] [Google Scholar]
  2. Bonkowsky H. L., Tschudy D. P., Collins A., Doherty J., Bossenmaier I., Cardinal R., Watson C. J. Repression of the overproduction of porphyrin precursors in acute intermittent porphyria by intravenous infusions of hematin. Proc Natl Acad Sci U S A. 1971 Nov;68(11):2725–2729. doi: 10.1073/pnas.68.11.2725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dhar G. J., Bossenmaier I., Petryka Z. J., Cardinal R., Watson C. J. Effects of hematin in hepatic porphyria. Further studies. Ann Intern Med. 1975 Jul;83(1):20–30. doi: 10.7326/0003-4819-83-1-20. [DOI] [PubMed] [Google Scholar]
  4. Elder G. H., Evans J. O., Thomas N. The primary enzyme defect in hereditary coproporphyria. Lancet. 1976 Dec 4;2(7997):1217–1219. doi: 10.1016/s0140-6736(76)91143-0. [DOI] [PubMed] [Google Scholar]
  5. GRANICK S., URATA G. Increase in activity of alpha-aminolevulinic acid synthetase in liver mitochondria induced by feeding of 3,5-dicarbethoxy-1,4-dihydrocollidine. J Biol Chem. 1963 Feb;238:821–827. [PubMed] [Google Scholar]
  6. Granick S. The induction in vitro of the synthesis of delta-aminolevulinic acid synthetase in chemical porphyria: a response to certain drugs, sex hormones, and foreign chemicals. J Biol Chem. 1966 Mar 25;241(6):1359–1375. [PubMed] [Google Scholar]
  7. Kaufman L., Marver H. S. Biochemical defects in two types of human hepatic porphyria. N Engl J Med. 1970 Oct 29;283(18):954–958. doi: 10.1056/NEJM197010292831803. [DOI] [PubMed] [Google Scholar]
  8. Lamon J., With T. K., Redeker A. G. The Hoesch test: bedside screening for urinary porphobilinogen in patients with suspected porphyria. Clin Chem. 1974 Nov;20(11):1438–1440. [PubMed] [Google Scholar]
  9. Maines M. D., Kappas A. Cobalt stimulation of heme degradation in the liver. Dissociation of microsomal oxidation of heme from cytochrome P-450. J Biol Chem. 1975 Jun 10;250(11):4171–4177. [PubMed] [Google Scholar]
  10. Miyagi K., Cardinal R., Bossenmaier I., Watson C. J. The serum porphobilinogen and hepatic porphobilinogen deaminase in normal and porphyric individuals. J Lab Clin Med. 1971 Nov;78(5):683–695. [PubMed] [Google Scholar]
  11. Peterson A., Bossenmaier I., Cardinal R., Watson C. J. Hematin treatment of acute porphyria. Early remission of an almost fatal relapse. JAMA. 1976 Feb 2;235(5):520–522. [PubMed] [Google Scholar]
  12. Pimstone N. R., Blekkenhorst G., Eales L. Enzymatic defects in hepatic porphyria. Preliminary observations in patients with porphyria cutanea tarda and variegate porphyria. Enzyme. 1973;16(1):354–366. [PubMed] [Google Scholar]
  13. Strand L. J., Felsher B. F., Redeker A. G., Marver H. S. Heme biosynthesis in intermittent acute prophyria: decreased hepatic conversion of porphobilinogen to porphyrins and increased delta aminolevulinic acid synthetase activity. Proc Natl Acad Sci U S A. 1970 Nov;67(3):1315–1320. doi: 10.1073/pnas.67.3.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. TSCHUDY D. P., PERLROTH M. G., MARVER H. S., COLLINS A., HUNTER G., Jr, RECHCIGL M., Jr ACUTE INTERMITTENT PORPHYRIA: THE FIRST "OVERPRODUCTION DISEASE" LOCALIZED TO A SPECIFIC ENZYME. Proc Natl Acad Sci U S A. 1965 Apr;53:841–847. doi: 10.1073/pnas.53.4.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. TSCHUDY D. P., WELLAND F. H., COLLINS A., HUNTER G., Jr THE EFFECT OF CARBOHYDRATE FEEDING ON THE INDUCTION OF DELTA-AMINOLEVULINIC ACID SYNTHETASE. Metabolism. 1964 May;13:396–406. doi: 10.1016/0026-0495(64)90113-1. [DOI] [PubMed] [Google Scholar]
  16. Tenhunen R., Marver H. S., Schmid R. The enzymatic conversion of hemoglobin to bilirubin. Trans Assoc Am Physicians. 1969;82:363–371. [PubMed] [Google Scholar]
  17. WATSON C. J., TADDEINI L., BOSSENMAIER I. PRESENT STATUS OF THE EHRLICH ALDEHYDE REACTION FOR URINARY PORPHOBILINOGEN. JAMA. 1964 Nov 9;190:501–504. doi: 10.1001/jama.1964.03070190021004. [DOI] [PubMed] [Google Scholar]
  18. Watson C. J., Bossenmaier I., Cardinal R., Petryka Z. J. Repression by hematin of porphyrin biosynthesis in erythrocyte precursors in congenital erythropoietic porphyria. Proc Natl Acad Sci U S A. 1974 Feb;71(2):278–282. doi: 10.1073/pnas.71.2.278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Watson C. J., Dhar G. J., Bossenmaier I., Cardinal R., Petryka Z. J. Effect of hematin in acute porphyric relapse. Ann Intern Med. 1973 Jul;79(1):80–83. doi: 10.7326/0003-4819-79-1-80. [DOI] [PubMed] [Google Scholar]
  20. Watson C. J. Editorial: Hematin and porphyria. N Engl J Med. 1975 Sep 18;293(12):605–607. doi: 10.1056/NEJM197509182931210. [DOI] [PubMed] [Google Scholar]
  21. Waxman A. D., Collins A., Tschudy D. P. Oscillations of hepatic delta-aminolevulinic acid synthetase produced in vivo by heme. Biochem Biophys Res Commun. 1966 Sep 8;24(5):675–683. doi: 10.1016/0006-291x(66)90377-9. [DOI] [PubMed] [Google Scholar]
  22. Zimmerman T. S., McMillin J. M., Watson C. J. Onset of manifestations of hepatic porphyria in relation to the influence of female sex hormones. Arch Intern Med. 1966 Sep;118(3):229–240. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES