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. 1983 May;71(5):1175–1182. doi: 10.1172/JCI110866

Iron and the liver: acute effects of iron-loading on hepatic heme synthesis of rats. Role of decreased activity of 5-aminolevulinate dehydrase.

H L Bonkowsky, J F Healey, P R Sinclair, J F Sinclair, S I Shedlofsky, G H Elder
PMCID: PMC436977  PMID: 6189858

Abstract

Acute iron loading of rats, by intraperitoneal administration of iron-dextran (500 mg Fe/kg body wt 18-20 h before killing) decreased by 30% the rate of conversion of 5-amino-[14C]levulinate ([14C]ALA) into heme as measured with a recently described procedure for liver homogenates (1981. Biochem. J. 198: 595-604). The decrease in conversion of labeled ALA into heme caused by iron loading was shown to be due to a 70-80% decrease in activity of ALA dehydrase. The decrease in activity of ALA dehydrase caused by iron loading was not associated with a decrease in hepatic concentrations of GSH, nor could it be reversed by addition of dithiothreitol, Zn2+ or chelators of Fe2+ and Fe3+. Addition of FeSO4, ferric citrate, or ferritin to homogenates of control liver had no effect of activity of ALA dehydrase. The decrease in activity of ALA dehydrase, caused by iron-dextran, was mirrored by a reciprocal increase in ALA synthase. Iron-dextran potentiated the induction of ALA synthase by allylisopropylacetamide. However, this potentiation could be dissociated from the decrease in ALA dehydrase caused by iron loading.

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Selected References

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

  1. Blekkenhorst G. H., Eales L., Pimstone N. R. Activation of uroporphyrinogen decarboxylase by ferrous iron in porphyria cutanea tarda. S Afr Med J. 1979 Nov 24;56(22):918–920. [PubMed] [Google Scholar]
  2. Bonkowsky H. L., Carpenter S. J., Healey J. F. Iron and the liver: subcellular distribution of iron and decreased microsomal cytochrome P-450 in livers of iron-loaded rats. Arch Pathol Lab Med. 1979 Jan;103(1):21–29. [PubMed] [Google Scholar]
  3. Bonkowsky H. L., Healey J. F., Sinclair P. R., Sinclair J. F., Pomeroy J. S. Iron and the liver. Acute and long-term effects of iron-loading on hepatic haem metabolism. Biochem J. 1981 Apr 15;196(1):57–64. doi: 10.1042/bj1960057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bonkowsky H. L., Sinclair P. R., Sinclair J. F. Hepatic heme metabolism and its control. Yale J Biol Med. 1979 Jan-Feb;52(1):13–37. [PMC free article] [PubMed] [Google Scholar]
  5. Buege J. A., Aust S. D. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302–310. doi: 10.1016/s0076-6879(78)52032-6. [DOI] [PubMed] [Google Scholar]
  6. Dailey H. A., Jr, Lascelles J. Reduction of iron and synthesis of protoheme by Spirillum itersonii and other organisms. J Bacteriol. 1977 Feb;129(2):815–820. doi: 10.1128/jb.129.2.815-820.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Doyle D., Schimke R. T. The genetic and developmental regulation of hepatic delta-aminolevulinate dehydratase in mice. J Biol Chem. 1969 Oct 25;244(20):5449–5459. [PubMed] [Google Scholar]
  8. Elder G. H., Wyvill P. C. Measurement of uroporphyrinogen decarboxylase using porphyrinogens prepared by chemical reduction. Enzyme. 1982;28(2-3):186–195. doi: 10.1159/000459101. [DOI] [PubMed] [Google Scholar]
  9. Healey J. F., Bonkowsky H. L., Sinclair P. R., Sinclair J. F. Conversion of 5-aminolaevulinate into haem by liver homogenates. Comparison of rat and chick embryo. Biochem J. 1981 Sep 15;198(3):595–604. doi: 10.1042/bj1980595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ibrahim N. G., Hoffstein S. T., Freedman M. L. Induction of liver cell haem oxygenase in iron-overloaded rats. Biochem J. 1979 May 15;180(2):257–263. doi: 10.1042/bj1800257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ibrahim N. G., Nelson J. C., Levere R. D. Control of delta-aminolaevulinate synthase and haem oxygenase in chronic-iron-overloaded rats. Biochem J. 1981 Oct 15;200(1):35–42. doi: 10.1042/bj2000035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. KEBERLE H. THE BIOCHEMISTRY OF DESFERRIOXAMINE AND ITS RELATION TO IRON METABOLISM. Ann N Y Acad Sci. 1964 Oct 7;119:758–768. doi: 10.1111/j.1749-6632.1965.tb54077.x. [DOI] [PubMed] [Google Scholar]
  13. Kushner J. P., Steinmuller D. P., Lee G. R. The role of iron in the pathogenesis of porphyria cutanea tarda. II. Inhibition of uroporphyrinogen decarboxylase. J Clin Invest. 1975 Sep;56(3):661–667. doi: 10.1172/JCI108136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Louw M., Neethling A. C., Percy V. A., Carstens M., Shanley B. C. Effects of hexachlorobenzene feeding and iron overload on enzymes of haem biosynthesis and cytochrome P 450 in rat liver. Clin Sci Mol Med. 1977 Aug;53(2):111–115. doi: 10.1042/cs0530111. [DOI] [PubMed] [Google Scholar]
  15. MAUZERALL D., GRANICK S. The occurrence and determination of delta-amino-levulinic acid and porphobilinogen in urine. J Biol Chem. 1956 Mar;219(1):435–446. [PubMed] [Google Scholar]
  16. Maines M. D. Role of trace metals in regulation of cellular heme and hemoprotein metabolism: sensitizing effects of chronic iron treatment on acute gold toxicity. Drug Metab Rev. 1979;9(2):237–255. doi: 10.3109/03602537908993893. [DOI] [PubMed] [Google Scholar]
  17. Sinclair P., Granick S. Two methods for determining the activity of delta-aminolevulinate synthetase within intact liver cells in culture. Anal Biochem. 1977 May 1;79(1-2):380–393. doi: 10.1016/0003-2697(77)90412-2. [DOI] [PubMed] [Google Scholar]
  18. Stein J. A., Tschudy D. P., Corcoran P. L., Collins A. Delta-aminolevulinic acid synthetase. 3. Synergistic effect of chelated iron on induction. J Biol Chem. 1970 May 10;245(9):2213–2218. [PubMed] [Google Scholar]
  19. Tschudy D. P., Hess R. A., Frykholm B. C. Inhibition of delta-aminolevulinic acid dehydrase by 4,6-dioxoheptanoic acid. J Biol Chem. 1981 Oct 10;256(19):9915–9923. [PubMed] [Google Scholar]
  20. Woods J. S., Kardish R., Fowler B. A. Studies on the action of porphyrinogenic trace metals on the activity of hepatic uroporphyrinogen decarboxylase. Biochem Biophys Res Commun. 1981 Nov 16;103(1):264–271. doi: 10.1016/0006-291x(81)91688-0. [DOI] [PubMed] [Google Scholar]

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