Inhibition of aromatic L-aminoacid decarboxylase in clonal pheochromocytoma PC12h cells by N-methyl-4-phenylpyridinium ion (MPP+).

Abstract

N-Methyl-4-phenylpyridinium ion (MPP+), a reaction product of a neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was found to inhibit aromatic L-aminoacid decarboxylase activity in rat clonal pheochromocytoma PC12h cells. The enzyme activity was enhanced to several folds by addition of a cofactor, pyridoxal phosphate, and MPP+ inhibited the enhancement of the activity by exogenously added pyridoxal phosphate. The inhibition was competitive to pyridoxal phosphate, and the Ki value of MPP+ was 26.7 +/- 0.4 microM, while the Km value of pyridoxal phosphate was 0.645 +/- 0.053 microM. The inhibition was partly irreversible. The enzyme sample was incubated with MPP+ and then dialyzed against phosphate buffer. After dialysis, the inhibited enzyme activity was only partly recovered by addition of pyridoxal phosphate, even though MPP+ was completely removed. Activity of other enzymes, tyrosine hydroxylase and monoamine oxidase could be recovered by dialysis. On the other hand, MPP+ did not affect the binding of the enzyme with the substrate, L-DOPA or 5-hydroxytryptophan.

• Authors: M Naoi, T Takahashi, H Ichinose, T Nagatsu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 152 Issue 1 Pg. 15-21 (Apr 15 1988) ISSN: 0006-291X [Print] United States
• PMID: 3258744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aromatic Amino Acid Decarboxylase Inhibitors
• Neurotoxins
• Pyridinium Compounds
• Pyridoxal Phosphate
• 1-Methyl-4-phenylpyridinium

Topics

• 1-Methyl-4-phenylpyridinium
• Adrenal Gland Neoplasms
• Animals
• Aromatic Amino Acid Decarboxylase Inhibitors
• Binding, Competitive
• Cell Line
• Kinetics
• Neurotoxins (pharmacology)
• Pheochromocytoma
• Pyridinium Compounds (pharmacology)
• Pyridoxal Phosphate (pharmacology)