Kinetic parameters of the inhibition of red blood cell aminolevulinic acid dehydratase by triethyl lead and its reversal by dithiothreitol and zinc.
In chronic or acute exposure to triethyl lead, a de novo synthesis of aminolevulinic acid dehydratase (delta-ALAD) in bone marrow and an increased activity in circulating red blood cells can be demonstrated by activating the enzyme with dithiothreitol (DTT) and zinc. We determined the median inhibitory concentration and the apparent inhibition constant for triethyl lead on delta-ALAD. After dosing with triethyl lead, in vivo inhibition of ALAD only occurred at the high dose, but activation analysis in vitro showed increased ALAD activity to be present at all dose levels in a dose-dependent fashion. The use of an activation assay for red blood cell ALAD may have value as a bio-effects monitor of exposure to organic lead.
D000818:Animals; D004229:Dithiothreitol / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009942:Organometallic Compounds / Q000097:blood / Q000633:toxicity*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors / Q000097:blood* / Q000378:metabolism; D051381:Rats; D015032:Zinc / Q000494:pharmacology*
D009942:Organometallic Compounds; C010360:triethyllead; D000623:Porphobilinogen Synthase; D015032:Zinc; D004229:Dithiothreitol