The site of inhibition of porphyrin biosynthesis by an isomer of diazinon in rats.
2-Isopropyl-6-methyl-4-S-pyrimidinyl diethyl thiophosphate (isodiazinon) has been synthesized by an unambiguous route. Rats treated with isodiazinon over a 100-day period show decreased levels of liver ferrochelatase. Rats treated with diazinon and isodiazinon in combination over the same period show a more marked decrease in liver ferrochelatase activity as well as a decrease in the activity of coproporphyrinogen oxidase. Treatment of rats with stabilised diazinon over the same period is not associated with a decrease in the activity of either enzyme. Neither diazinon nor isodiazinon causes a decrease in the activity of glutamate dehydrogenase, succinate dehydrogenase or kynurenine hydroxylase, suggesting that the effect is specific to the porphyrin biosynthesis pathway and not due to mitochondrial damage.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D003304:Coproporphyrinogen Oxidase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003976:Diazinon / Q000138:chemical synthesis / Q000494:pharmacology*; D005243:Feces / Q000032:analysis; D005260:Female; D005294:Ferrochelatase / Q000378:metabolism; D011163:Hydroxymethylbilane Synthase / Q000378:metabolism; D007202:Indicators and Reagents; D007306:Insecticides / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D000623:Porphobilinogen Synthase / Q000378:metabolism; D011166:Porphyrins / Q000096:biosynthesis* / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism
D007202:Indicators and Reagents; D007306:Insecticides; D011166:Porphyrins; C039331:isodiazinon; D003577:Cytochrome P-450 Enzyme System; D003304:Coproporphyrinogen Oxidase; D000624:5-Aminolevulinate Synthetase; D011163:Hydroxymethylbilane Synthase; D014575:Uroporphyrinogen Decarboxylase; D000623:Porphobilinogen Synthase; D005294:Ferrochelatase; D003976:Diazinon