Deuterium isotope effect measurements on the interactions of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with monoamine oxidase B

Journal Article · Tue Aug 15 04:00:00 EDT 1989 · Journal of Biological Chemistry; (USA)

OSTI ID:5160517

Ottoboni, S; Caldera, P; Trevor, A; Castagnoli, N Jr ^[1]

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1. Univ. of California, San Francisco (USA)

Kinetic deuterium isotope effects for the noncompetitive, intermolecular monoamine oxidase B-catalyzed oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the corresponding 1-methyl-4-phenyl-2,3-dihydropyridinium species MPDP+ were found to be 3.55 on Vmax and 8.01 on Vmax/Km with MPTP-6,6-d2 as the deuterated substrate. Similar values were obtained with MPTP-2,2,6-d4 and MPTP-CD3-2,2,6,6-d4. The deuterium isotope effect for the electrochemical oxidation of 1 mM MPTP-2,2,6,6-d4 was only 1.35. These results indicate that the monoamine oxidase B-catalyzed oxidation of this substrate may not proceed via a reaction pathway involving alpha-carbon deprotonation of an aminium radical intermediate. Isotope effect measurements also established that the rate of inactivation of monoamine oxidase B by MPTP is unaffected by replacement of the C-6 methylene protons with deuterons, but is retarded by replacement of the C-2 methylene protons (DKi = 1.9). The mechanism-based inactivation of monoamine oxidase B by MPTP, therefore, is likely to mediated by a species derived from the enzyme-generated 2,3-dihydropyridinium oxidation product.

• OSTI ID: 5160517
• Journal Information: Journal of Biological Chemistry; (USA), Journal Name: Journal of Biological Chemistry; (USA) Vol. 264:23; ISSN JBCHA; ISSN 0021-9258
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
AMINE OXIDASES
ANIMALS
ANTIGENS
AZINES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
CATTLE
CHEMICAL REACTIONS
CHROMATOGRAPHY
DEUTERIUM
DOMESTIC ANIMALS
ENZYMES
HETEROCYCLIC COMPOUNDS
HYDROGEN ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPE EFFECTS
ISOTOPES
KINETICS
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MASS SPECTRA
MATERIALS
METABOLISM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDATION
OXIDOREDUCTASES
PYRIDINES
REACTION KINETICS
RUMINANTS
SEPARATION PROCESSES
SPECTRA
STABLE ISOTOPES
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
VERTEBRATES