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Evidence oftheinduction ofdenovo synthesis of 5-aminolaevulinate dehydratase bylead

Hideaki Fujita, Naoko Ishihara

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Abstract

Inhibition of&-aminolaevulinate (ALA)dehydratase (porphobilinogen synthase: EC 4.2.1.24) coupled with an increase intheenzyme concentration was observed intheliver ofrats exposed tolead bymouthfor150days. ALA dehydratase concentration increased by25% inrats exposed toleadandcell free translation alsoshowed an increase indenovo synthesis ofALA dehydratase by20%intheliver ofratsexposed tolead. Theaddition ofleadinvitro tothecell free translation systemhadno effect on thedenovo synthesis ofALAdehydratase. Theseresults suggest that exposuretolead caused atranscription dependent induction ofALA dehydratase whichmight compensate forthe enzyme inhibition bylead. Delta-aminolaevulinate (ALA)dehydratase (por- phobilinogen synthase:EC4.2.1.24) iswellknownto beinhibited bylead viamercaptide formation,' and theinhibition ofALA dehydratase activity inperi- pheral erythrocytes iswell recognised asoneofthe mostsensitive indicators ofexposure tolead.2-5 The enzymeplays a limiting partinhaemmetabolism under someconditions6 andthedenovosynthesis of theenzymeprotein mayoccurtocompensate the enzymeinhibition bylead. In1978MaesandGeber reported aphenomenal increase inALAdehydratase activity intheperipheral erythrocytes oflead treated animals8 whichwasconsidered tobeduetothe chelation ofleadbyphosphate usedintheenzyme assay andtoanincrease inthedehydratase concen- tration,9 whichseemstoresult fromanincrease in Iyoung erythrocytes.'

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Inhibition of&-aminolaevulinate (ALA)dehydratase (porphobilinogen synthase: EC 4.2.1.24) coupled with an increase intheenzyme concentration was observed intheliver ofrats exposed tolead bymouthfor150days. ALA dehydratase concentration increased by25% inrats exposed toleadandcell free translation alsoshowed an increase indenovo synthesis ofALA dehydratase by20%intheliver ofratsexposed tolead. Theaddition ofleadinvitro tothecell free translation systemhadno effect on thedenovo synthesis ofALAdehydratase. Theseresults suggest that exposuretolead caused atranscription dependent induction ofALA dehydratase whichmight compensate forthe enzyme inhibition bylead. Delta-aminolaevulinate (ALA)dehydratase (por- phobilinogen synthase:EC4.2.1.24) iswellknownto beinhibited bylead viamercaptide formation,' and theinhibition ofALA dehydratase activity inperi- pheral erythrocytes iswell recognised asoneofthe mostsensitive indicators ofexposure tolead.2-5 The enzymeplays a limiting partinhaemmetabolism under someconditions6 andthedenovosynthesis of theenzymeprotein mayoccurtocompensate the enzymeinhibition bylead. In1978MaesandGeber reported aphenomenal increase inALAdehydratase activity intheperipheral erythrocytes oflead treated animals8 whichwasconsidered tobeduetothe chelation ofleadbyphosphate usedintheenzyme assay andtoanincrease inthedehydratase concen- tration,9 whichseemstoresult fromanincrease in Iyoung erythrocytes.'

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Available abstract

Inhibition of&-aminolaevulinate (ALA)dehydratase (porphobilinogen synthase: EC 4.2.1.24) coupled with an increase intheenzyme concentration was observed intheliver ofrats exposed tolead bymouthfor150days. ALA dehydratase concentration increased by25% inrats exposed toleadandcell free translation alsoshowed an increase indenovo synthesis ofALA dehydratase by20%intheliver ofratsexposed tolead. Theaddition ofleadinvitro tothecell free translation systemhadno effect on thedenovo synthesis ofALAdehydratase. Theseresults suggest that exposuretolead caused atranscription dependent induction ofALA dehydratase whichmight compensate forthe enzyme inhibition bylead. Delta-aminolaevulinate (ALA)dehydratase (por- phobilinogen synthase:EC4.2.1.24) iswellknownto beinhibited bylead viamercaptide formation,' and theinhibition ofALA dehydratase activity inperi- pheral erythrocytes iswell recognised asoneofthe mostsensitive indicators ofexposure tolead.2-5 The enzymeplays a limiting partinhaemmetabolism under someconditions6 andthedenovosynthesis of theenzymeprotein mayoccurtocompensate the enzymeinhibition bylead. In1978MaesandGeber reported aphenomenal increase inALAdehydratase activity intheperipheral erythrocytes oflead treated animals8 whichwasconsidered tobeduetothe chelation ofleadbyphosphate usedintheenzyme assay andtoanincrease inthedehydratase concen- tration,9 whichseemstoresult fromanincrease in Iyoung erythrocytes.'

Key concepts: Dehydratase, Porphobilinogen synthase, Enzyme, Porphobilinogen, Chemistry, Biochemistry, Limiting, Enzyme assay

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