Mechanism of irreversible inactivation of phenylalanine-4- and tryptophan-5-hydroxylases by [4-36Cl, 2-14C]p-chlorophenylalanine: a revision.
Intraperitoneal injection of [4-36Cl, 2-14C]p-chlorophenylalanine (pCPA) (300 mg/kg) in rats revealed absence of chlorine in pure hepatic phenylalanine hydroxyase, while the carbon label appeared a 1--4 moles/mole of [14C]tyrosine in the inactivated phenylalanine and cerebral tryptophan-5-hydroxylase. Crystalline muscle aldolase and tyrosine hydroxylase also revealed the presence of [2-14C]tyrosine from [2-14C]pCPA without inactivating these enzymes. Injection of L-[(U)-14C] tyrosine led to its incorporation into the above enzymes, but to a different degree without altering the enzyme activity. Repeated injections of p-chlorophenylacetic acid had no effect on phenylalanine or tryptophan-hydroxylase, Administration of pCPA did not change the levels of cerebral biopterins. Reexamination of the effect of cycloheximide on reversing enzymic inactivation by pCPA failed to confirm our earlier observation.
D000818:Animals; D001708:Biopterins / Q000032:analysis; D001921:Brain / Q000201:enzymology*; D002250:Carbon Radioisotopes; D002713:Chlorine; D010134:Fenclonine / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D010651:Phenylalanine Hydroxylase / Q000037:antagonists & inhibitors*; D011868:Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors*
D002250:Carbon Radioisotopes; D011868:Radioisotopes; D001708:Biopterins; D002713:Chlorine; D010651:Phenylalanine Hydroxylase; D014365:Tryptophan Hydroxylase; D010134:Fenclonine