Abstract |
A variety of prophyrinogenic compounds were tested for their effect in ovo on chick-embryo liver microsomal cytochrome P-450 haem concentration and mitochondrial delta-aminolaevulinate synthase activity. With all drugs tested, there was a 30--50% decrease in cytochrome P-450 haem concentration within 1 h of treatment, and this was closely followed by an increase in delta-aminolaevulinate synthase activity. The relationship was independent of the extent of enzyme induction and is consistent with the proposal that drug-mediated destruction of cytochrome P-450 haem is the primary mechanism of induction of delta-aminolaevulinate synthase. After induction, synthesis of delta-aminolaevulinate synthase could be maintained by inhibiting further haem synthesis. These studies suggest that induction of porphyria is a combination of two distinct processes: (a) induction of delta-aminolaevulinate synthase synthesis by destruction of cytochrome P-450 haem and consequent depletion of cellular free haem; (b) maintenance of continued delta-aminolaevulinate synthase synthesis by preventing replenishment of cellular haem either by inhibiting haem synthesis and/or by promoting continuous removal of newly synthesized haem.
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Authors | L K Lim, G Srivastava, J D Brooker, B K May, W H Elliott |
Journal | The Biochemical journal
(Biochem J)
Vol. 190
Issue 3
Pg. 519-26
(Sep 15 1980)
ISSN: 0264-6021 [Print] England |
PMID | 7470066
(Publication Type: Journal Article)
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Chemical References |
- Allylisopropylacetamide
- Heme
- Dicarbethoxydihydrocollidine
- Hemin
- Cytochrome P-450 Enzyme System
- Proadifen
- 5-Aminolevulinate Synthetase
- Deferoxamine
- Phenobarbital
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Topics |
- 5-Aminolevulinate Synthetase
(biosynthesis)
- Allylisopropylacetamide
(pharmacology)
- Animals
- Chick Embryo
- Cytochrome P-450 Enzyme System
(metabolism)
- Deferoxamine
(pharmacology)
- Dicarbethoxydihydrocollidine
(pharmacology)
- Enzyme Induction
(drug effects)
- Heme
(metabolism)
- Hemin
(pharmacology)
- Microsomes, Liver
(drug effects, enzymology)
- Phenobarbital
(pharmacology)
- Porphyrias
(chemically induced)
- Proadifen
(pharmacology)
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