Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine inhibits proton motive force in energized liver mitochondria

Journal Article · · Archives of Biochemistry and Biophysics; (USA)
; ; ; ;  [1]
  1. National Heart, Lung and Blood Institute, Bethesda, MD (USA)
+ Show Author Affiliations

It is known that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which induces Parkinson's-like disease in primates and humans, depletes hepatocytes of ATP and subsequently causes cell death. Incubation of rat liver mitochondria with MPTP and 1-methyl-4-phenyl pyridinium ion (MPP+) significantly inhibited incorporation of {sup 32}Pi into ATP. MPTP and MPP+ inhibited the development of membrane potential and pH gradient in energized rat liver mitochondria, suggesting that reduction of the proton motive force may have reduced ATP synthesis. Since deprenyl, an inhibitor of monoamine oxidase, prevented the formation of MPP+ and inhibited the decrease in membrane potential caused by MPTP, but not that caused by MPP+, these effects of MPTP, as well as cell death, probably were mediated by MPP+. This mechanism may play a role in the specific loss of dopaminergic neurons resulting in MPTP-induced Parkinson's disease.

OSTI ID:
5405252
Journal Information:
Archives of Biochemistry and Biophysics; (USA), Journal Name: Archives of Biochemistry and Biophysics; (USA) Vol. 271:1; ISSN ABBIA; ISSN 0003-9861
Country of Publication:
United States
Language:
English

Similar Records

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP/sup +/) cause rapid ATP depletion in isolated hepatocytes
Journal Article · Thu May 29 00:00:00 EDT 1986 · Biochem. Biophys. Res. Commun.; (United States) · OSTI ID:5003039
MPTP: an industrial chemical and contaminant of illicit narcotics stimulates a new era in research on Parkinson's disease
Journal Article · Sat Oct 31 23:00:00 EST 1987 · Environ. Health Perspect.; (United States) · OSTI ID:5193867
Synthesis and biological activity of analogs of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its monoamine oxidase-derived metabolites
Thesis/Dissertation · Sat Dec 31 23:00:00 EST 1988 · OSTI ID:6531658

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
ATP
AZINES
BARYONS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
CELL CONSTITUENTS
DAYS LIVING RADIOISOTOPES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
ELEMENTARY PARTICLES
ENZYME INHIBITORS
FERMIONS
HADRONS
HETEROCYCLIC COMPOUNDS
INHIBITION
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
LIVER CELLS
MAMMALS
METABOLISM
MITOCHONDRIA
NERVOUS SYSTEM DISEASES
NUCLEI
NUCLEONS
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
PATHOGENESIS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PROTONS
PYRIDINES
PYRIDINIUM COMPOUNDS
QUATERNARY COMPOUNDS
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
SOMATIC CELLS
SYNTHESIS
TRACER TECHNIQUES
VERTEBRATES