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. 1972 Oct;129(5):1095–1099. doi: 10.1042/bj1291095

The effect of exogenous δ-aminolaevulinate on rat liver haem and cytochromes

Robert Druyan 1, Aldon Kelly 1
PMCID: PMC1174267  PMID: 4656595

Abstract

The activity of δ-aminolaevulinate synthetase is generally regarded as rate-limiting for hepatic haem biosynthesis. It has been suggested that cytochrome synthesis may also be regulated by changes in δ-aminolaevulinate synthetase activity. This hypothesis was studied by injecting product, δ-aminolaevulinate, into adult rats over a 4–240h period. The concentrations of hepatic mitochondrial cytochromes a, b, c and c1 were unchanged by treatment with δ-aminolaevulinate, allylisopropylacetamide or phenobarbital. In control animals, total microsomal haem content equalled the sum of cytochromes b5 plus P-450. After δ-aminolaevulinate administration the total amount of microsomal haem, measured as the pyridine haemochromogen, exceeded these components, indicating the formation of a `free' haem pool. Haem synthesis does not appear rate-limiting for hepatic cytochrome synthesis in the adult rat.

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Selected References

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

  1. Aschenbrenner B., Druyan R., Albin R., Rabinowitz M. Haem a, cytochrome c and total protein turnover in mitochondria from rat heart and liver. Biochem J. 1970 Sep;119(2):157–160. doi: 10.1042/bj1190157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnes R., Jones M. S., Jones O. T., Porra R. J. Ferrochelatase and -aminolaevulate synthetase in brain, heart, kidney and liver of normal and porphyric rats. The induction of -aminolaevulate synthetase in kidney cytosol and mitochondria by allylisopropylacetamide. Biochem J. 1971 Sep;124(3):633–637. doi: 10.1042/bj1240633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beattie D. S. Enzyme localization in the inner and outer membranes of rat liver mitochondria. Biochem Biophys Res Commun. 1968 Jun 28;31(6):901–907. doi: 10.1016/0006-291x(68)90537-8. [DOI] [PubMed] [Google Scholar]
  4. Beattie D. S., Stuchell R. N. Studies on the induction of hepatic delta-aminolevulinic acid synthetase in rat liver mitochondria. Arch Biochem Biophys. 1970 Aug;139(2):291–297. doi: 10.1016/0003-9861(70)90480-7. [DOI] [PubMed] [Google Scholar]
  5. Beattie D. S. The possible relationship between heme synthesis and mitochondrial biogenesis. Arch Biochem Biophys. 1971 Nov;147(1):136–142. doi: 10.1016/0003-9861(71)90319-5. [DOI] [PubMed] [Google Scholar]
  6. De Matteis F. Loss of haem in rat liver caused by the porphyrogenic agent 2-allyl-2-isopropylacetamide. Biochem J. 1971 Oct;124(4):767–777. doi: 10.1042/bj1240767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Druyan R., DeBernard B., Rabinowitz M. Turnover of cytochromes labeled with delta-aminolevulinic acid-3H in rat liver. J Biol Chem. 1969 Nov 10;244(21):5874–5878. [PubMed] [Google Scholar]
  8. GORNALL A. G., BARDAWILL C. J., DAVID M. M. Determination of serum proteins by means of the biuret reaction. J Biol Chem. 1949 Feb;177(2):751–766. [PubMed] [Google Scholar]
  9. 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]
  10. Garner R. C., McLean A. E. Separation of haem incorporation from protein synthesis in liver microsomes. Biochem Biophys Res Commun. 1969 Dec 4;37(6):883–887. doi: 10.1016/0006-291x(69)90213-7. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Hayashi N., Kurashima Y., Kikuchi G. Mechanism of allylisopropylacetamide-induced increase of -aminolevulinate synthetase in liver mitochondria. V. Mechanism of regulation by hemin of the level of -aminolevulinate synthetase in rat liver mitochondria. Arch Biochem Biophys. 1972 Jan;148(1):10–21. doi: 10.1016/0003-9861(72)90109-9. [DOI] [PubMed] [Google Scholar]
  13. Jones M. S., Jones O. T. The structural organization of haem synthesis in rat liver mitochondria. Biochem J. 1969 Jul;113(3):507–514. doi: 10.1042/bj1130507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Levere R. D., Granick S. Control of hemoglobin synthesis in the cultured chick blastoderm by delta-aminolevulinic acid synthetase: increase in the rate of hemoglobin formation with delta-aminolevulinic acid. Proc Natl Acad Sci U S A. 1965 Jul;54(1):134–137. doi: 10.1073/pnas.54.1.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Levin W., Kuntzman R. Biphasic decrease of radioactive hemoprotein from liver microsomal CO-binding particles. Effect of 3-methylcholanthrene. J Biol Chem. 1969 Jul 10;244(13):3671–3676. [PubMed] [Google Scholar]
  16. Levitt M., Schacter B. A., Zipursky A., Israels L. G. The nonerythropoietic component of early bilirubin. J Clin Invest. 1968 Jun;47(6):1281–1294. doi: 10.1172/JCI105820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Marver H. S., Collins A., Tschudy D. P., Rechcigl M., Jr Delta-aminolevulinic acid synthetase. II. Induction in rat liver. J Biol Chem. 1966 Oct 10;241(19):4323–4329. [PubMed] [Google Scholar]
  18. Marver H. S., Tschudy D. P., Perlroth M. G., Collins A. Coordinate synthesis of heme and apoenzyme in the formation of tryptophan pyrrolase. Science. 1966 Oct 28;154(3748):501–503. doi: 10.1126/science.154.3748.501. [DOI] [PubMed] [Google Scholar]
  19. McKay R., Druyan R., Getz G. S., Rabinowitz M. Intramitochondrial localization of delta-aminolaevulate synthetase and ferrochelatase in rat liver. Biochem J. 1969 Sep;114(3):455–461. doi: 10.1042/bj1140455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. OMURA T., SATO R. THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. I. EVIDENCE FOR ITS HEMOPROTEIN NATURE. J Biol Chem. 1964 Jul;239:2370–2378. [PubMed] [Google Scholar]
  21. Orrenius S., Ernster L. Phenobarbital-induced synthesis of the oxidative demethylating enzymes of rat liver microsomes. Biochem Biophys Res Commun. 1964 May 22;16(1):60–65. doi: 10.1016/0006-291x(64)90211-6. [DOI] [PubMed] [Google Scholar]
  22. PORRA R. J., JONES O. T. Studies on ferrochelatase. 1. Assay and properties of ferrochelatase from a pig-liver mitochondrial extract. Biochem J. 1963 Apr;87:181–185. doi: 10.1042/bj0870181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sholnick P. L., Hammaker L. E., Marver H. S. Soluble hepatic delta-aminolevulinic acid synthetase: end-product inhibition of the partially purified enzyme. Proc Natl Acad Sci U S A. 1969 May;63(1):65–70. doi: 10.1073/pnas.63.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Soslau G., Stotz E. H., Lockshin R. A. Stimulation of cytochrome c synthesis in the developing Polyphemus moth by -aminolevulinic acid. Biochemistry. 1971 Aug 17;10(17):3296–3299. doi: 10.1021/bi00793a021. [DOI] [PubMed] [Google Scholar]
  25. URATA G., GRANICK S. Biosynthesis of alpha-aminoketones and the metabolism of aminoacetone. J Biol Chem. 1963 Feb;238:811–820. [PubMed] [Google Scholar]
  26. WILLIAMS J. N., Jr A METHOD FOR THE SIMULTANEOUS QUANTITATIVE ESTIMATION OF CYTOCHROMES A, B, C1, AND C IN MITOCHONDRIA. Arch Biochem Biophys. 1964 Sep;107:537–543. doi: 10.1016/0003-9861(64)90313-3. [DOI] [PubMed] [Google Scholar]
  27. Waterfield M. D., Del Favero A., Gray C. H. Effect of 1,4-dihydro-3,5-dicarbethoxycollidine on hepatic microsomal haem, cytochrome b5 and cytochrome P450 in rabbits and mice. Biochim Biophys Acta. 1969 Jul 30;184(2):470–473. doi: 10.1016/0304-4165(69)90054-3. [DOI] [PubMed] [Google Scholar]

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