Porphyrogenic effects and induction of heme oxygenase in vivo by δ-aminolevulinic acid

Karl Anderson, George S. Drummond, Umberto Freddara, Mohinder K. Sardana, Shigeru Sassa

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The effects of single large doses of the porphyrin-heme precursor ḡd-aminolevulinic acid on tissue porphyrins and on δ-aminolevulinate synthase and heme oxygenase, the rate-living enzymes of liver heme synthesis and degradation respectively, were studied in the chick embryo in ovo, in the mouse and in the rat. δ-Aminolevulinic acid treatment produced a distinctive pattern characterized by extensive tissue porphyrin accumulation and alterations in these rate-limiting enzymes in the liver. Repression of basal or allylisopropylacetamide-induced liver δ-aminolevulinate synthase was observed and, in the mouse and the rat, induction of liver heme oxygenase after δ-aminolevulinic acid treatment, in a manner similar to the known effects of hemin on these enzymes. In the chick embryo liver in ovo heme oxygenase was substantially higher than in rat and mouse liver, and was not significantly induced by δ-aminolevulinic acid or other compounds, including hemin, CS2 and CoCl2. Levulinic acid, an analogue of δ-aminolevulinic acid, did not induce heme oxygenase in mouse liver. δ-Aminolevunilic acid treatment did not impair ferrochelatase activity but was associated with slight and variable decreases in liver cytochrome P-450. Treatment of chick embryos with a small 'priming' dose of 1,4-dihydro-3,5-dicarbethoxycollidine, which impairs liver ferrochelatase activity, accentuated porphyrin accumulation after δ-aminolevulinic acid in the liver. These observations indicate that exogenous δ-aminolevulinic acid is metabolized to porphyrins in a number of tissues and, at least in the liver, to a physiologically significant amount of heme, thereby producing an increase in the size of one or more of the heme pools that regulate both heme systhesis and degradation. It is also possible than when δ-aminolevulinic acid is markedly overproduced in vivo it may be transported to many tissues and re-enter the heme pathway and alter porphyrin-heme metabolism in cells and tissues other than those in which its overproduction primarily occurs.

Original languageEnglish (US)
Pages (from-to)289-299
Number of pages11
JournalBBA - General Subjects
Volume676
Issue number3
DOIs
StatePublished - Sep 4 1981
Externally publishedYes

Fingerprint

Heme Oxygenase (Decyclizing)
Aminolevulinic Acid
Liver
Heme
Porphyrins
Tissue
Chick Embryo
Ferrochelatase
Rats
Hemin
Allylisopropylacetamide
Enzymes
Degradation
Metabolism
Cytochrome P-450 Enzyme System

Keywords

  • (Liver)
  • Heme oxygenase
  • Porphyrin-heme metabolism
  • δ-Aminolevulinate synthase
  • δ-Aminolevulinic acid

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology
  • Medicine(all)

Cite this

Porphyrogenic effects and induction of heme oxygenase in vivo by δ-aminolevulinic acid. / Anderson, Karl; Drummond, George S.; Freddara, Umberto; Sardana, Mohinder K.; Sassa, Shigeru.

In: BBA - General Subjects, Vol. 676, No. 3, 04.09.1981, p. 289-299.

Research output: Contribution to journalArticle

Anderson, Karl ; Drummond, George S. ; Freddara, Umberto ; Sardana, Mohinder K. ; Sassa, Shigeru. / Porphyrogenic effects and induction of heme oxygenase in vivo by δ-aminolevulinic acid. In: BBA - General Subjects. 1981 ; Vol. 676, No. 3. pp. 289-299.
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