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Titolo:
Peroxynitrite inactivates tryptophan hydroxylase via sulfhydryl oxidation - Coincident nitration of enzyme tyrosyl residues has minimal impact on catalytic activity
Autore:
Kuhn, DM; Geddes, TJ;
Indirizzi:
Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA Wayne State Univ Detroit MI USA 48201 hav Neurosci, Detroit, MI 48201 USA Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA Wayne State Univ Detroit MI USA 48201 Med & Genet, Detroit, MI 48201 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 42, volume: 274, anno: 1999,
pagine: 29726 - 29732
SICI:
0021-9258(19991015)274:42<29726:PITHVS>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEURONAL NITRIC-OXIDE; SUPEROXIDE-DISMUTASE; CARBON-DIOXIDE; DOPAMINERGIC NEUROTOXICITY; SEROTONIN NEURONS; MDMA ECSTASY; BRAIN; METHAMPHETAMINE; ACID; PROTEINS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
60
Recensione:
Indirizzi per estratti:
Indirizzo: Kuhn, DM 2125 Scott Hall,540 E Canfield, Detroit, MI 48201 USA 2125 ScottHall,540 E Canfield Detroit MI USA 48201 MI 48201 USA
Citazione:
D.M. Kuhn e T.J. Geddes, "Peroxynitrite inactivates tryptophan hydroxylase via sulfhydryl oxidation - Coincident nitration of enzyme tyrosyl residues has minimal impact on catalytic activity", J BIOL CHEM, 274(42), 1999, pp. 29726-29732

Abstract

Tryptophan hydroxylase, the initial and rate-limiting enzyme in serotonin biosynthesis, is inactivated by peroxynitrite in a concentration-dependent manner. This effect is prevented by molecules that react directly with peroxynitrite such as dithiothreitol, cysteine, glutathione, methionine tryptophan, and uric acid but not by scavengers of superoxide (superoxide dismutase), hydroxyl radical (Me2SO, mannitol), and hydrogen peroxide (catalase), Assuming simple competition kinetics between peroxynitrite scavengers and the enzyme, a second-order rate constant of 3.4 x 10(4) M-1 s(-1) at 25 degrees C and pH 7.4 was estimated. The peroxynitrite-induced loss of enzyme activity was accompanied by a concentration-dependent oxidation of protein sulfhydryl groups, Peroxynitrite-modified tryptophan hydroxylase was resistantto reduction by arsenite, borohydride, and dithiothreitol, suggesting thatsulfhydryls were oxidized beyond sulfenic acid. Peroxynitrite also caused the nitration of tyrosyl residues in tryptophan hydroxylase, with a maximalmodification of 3.8 tyrosines/monomer, Sodium bicarbonate protected tryptophan hydroxylase from peroxynitrite-induced inactivation and lessened the extent of sulfhydryl oxidation while causing a 2-fold increase in tyrosine nitration, Tetranitromethane, which oxidizes sulfhydryls at pH 6 or 8, but which nitrates tyrosyl residues at pH 8 only, inhibited tryptophan hydroxylase equally at either pH, Acetylation of tyrosyl residues with N-acetylimidazole did not alter tryptophan hydroxylase activity, These data suggest thatperoxynitrite inactivates tryptophan hydroxylase via sulfhydryl oxidation,Modification of tyrosyl residues by peroxynitrite plays a relatively minorrole in the inhibition of tryptophan hydroxylase catalytic activity.

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Documento generato il 31/03/20 alle ore 22:02:52