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Article: Evidence that in chick embryos destruction of hepatic microsomal cytochrome P-450 haem is a general mechanism of induction of δ-aminolaevulinate synthase by porphyria-causing drugs

TitleEvidence that in chick embryos destruction of hepatic microsomal cytochrome P-450 haem is a general mechanism of induction of δ-aminolaevulinate synthase by porphyria-causing drugs
Authors
Issue Date1980
PublisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.org
Citation
Biochemical Journal, 1980, v. 190 n. 3, p. 519-526 How to Cite?
AbstractA variety of porphyrinogenic compounds were tested for their effect in ovo on chick-embryo liver microsomal cytochrome P-450 haem concentration and mitochondrial δ-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 δ-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 δ-aminolaevulinate synthase. After induction, synthesis of δ-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 δ-aminolaevulinate synthase synthesis by destruction of cytochrome P-450 haem and consequent depletion of cellular free haem; (b) maintenance of continued δ-aminolaevulinate synthase synthesis by preventing replenishment of cellular haem either by inhibiting haem synthesis and/or by promoting continuous removal of newly synthesized haem.
Persistent Identifierhttp://hdl.handle.net/10722/147728
ISSN
2015 Impact Factor: 3.562
2015 SCImago Journal Rankings: 2.582
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLim, LKen_US
dc.contributor.authorSrivastava, Gen_US
dc.contributor.authorBrooker, JDen_US
dc.date.accessioned2012-05-29T06:08:56Z-
dc.date.available2012-05-29T06:08:56Z-
dc.date.issued1980en_US
dc.identifier.citationBiochemical Journal, 1980, v. 190 n. 3, p. 519-526en_US
dc.identifier.issn0264-6021en_US
dc.identifier.urihttp://hdl.handle.net/10722/147728-
dc.description.abstractA variety of porphyrinogenic compounds were tested for their effect in ovo on chick-embryo liver microsomal cytochrome P-450 haem concentration and mitochondrial δ-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 δ-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 δ-aminolaevulinate synthase. After induction, synthesis of δ-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 δ-aminolaevulinate synthase synthesis by destruction of cytochrome P-450 haem and consequent depletion of cellular free haem; (b) maintenance of continued δ-aminolaevulinate synthase synthesis by preventing replenishment of cellular haem either by inhibiting haem synthesis and/or by promoting continuous removal of newly synthesized haem.en_US
dc.languageengen_US
dc.publisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.orgen_US
dc.relation.ispartofBiochemical Journalen_US
dc.subject.mesh5-Aminolevulinate Synthetase - Biosynthesisen_US
dc.subject.meshAllylisopropylacetamide - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshChick Embryoen_US
dc.subject.meshCytochrome P-450 Enzyme System - Metabolismen_US
dc.subject.meshDeferoxamine - Pharmacologyen_US
dc.subject.meshDicarbethoxydihydrocollidine - Pharmacologyen_US
dc.subject.meshEnzyme Induction - Drug Effectsen_US
dc.subject.meshHeme - Metabolismen_US
dc.subject.meshHemin - Pharmacologyen_US
dc.subject.meshMicrosomes, Liver - Drug Effects - Enzymologyen_US
dc.subject.meshPhenobarbital - Pharmacologyen_US
dc.subject.meshPorphyrias - Chemically Induceden_US
dc.subject.meshProadifen - Pharmacologyen_US
dc.titleEvidence that in chick embryos destruction of hepatic microsomal cytochrome P-450 haem is a general mechanism of induction of δ-aminolaevulinate synthase by porphyria-causing drugsen_US
dc.typeArticleen_US
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_US
dc.identifier.authoritySrivastava, G=rp00365en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid7470066-
dc.identifier.scopuseid_2-s2.0-0019216721en_US
dc.identifier.volume190en_US
dc.identifier.issue3en_US
dc.identifier.spage519en_US
dc.identifier.epage526en_US
dc.identifier.isiWOS:A1980KK23300005-
dc.publisher.placeUnited Kingdomen_US

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