PMID: 11900856Mar 20, 2002Paper

Phenylethanolamine N-methyltransferase has beta-carboline 2N-methyltransferase activity: hypothetical relevance to Parkinson's disease

Neurochemistry International
Debra A GearhartMichael A Collins

Abstract

Mammalian brain has a beta-carboline 2N-methyltransferase activity that converts beta-carbolines, such as norharman and harman, into 2N-methylated beta-carbolinium cations, which are structural and functional analogs of the Parkinsonian-inducing toxin 1-methyl-4-phenylpyridinium cation (MPP+). The identity and physiological function of this beta-carboline 2N-methylation activity was previously unknown. We report pharmacological and biochemical evidence that phenylethanolamine N-methyltransferase (EC 2.1.1.28) has beta-carboline 2N-methyltransferase activity. Specifically, purified phenylethanolamine N-methyltransferase (PNMT) catalyzes the 2N-methylation (21.1 pmol/h per unit PNMT) of 9-methylnorharman, but not the 9N-methylation of 2-methylnorharmanium cation. LY134046, a selective inhibitor of phenylethanolamine N-methyltransferase, inhibits (IC50 1.9 microM) the 2N-methylation of 9-methylnorharman, a substrate for beta-carboline 2N-methyltransferase. Substrates of phenylethanolamine N-methyltransferase also inhibit beta-carboline 2N-methyltransferase activity in a concentration-dependent manner. beta-Carboline 2N-methyltransferase activity (43.7pmol/h/mg protein) is present in human adrenal medulla, a tissue with high phenyl...Continue Reading

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Citations

Aug 30, 2002·Neurotoxicology and Teratology·Kazuo MatsubaraToshio Awaya
Sep 10, 2002·Parkinsonism & Related Disorders·Michael A Collins
Feb 23, 2011·International Journal of Molecular Sciences·Elizabeth A MazzioKaram F A Soliman
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Dec 16, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·David J WagnerJoanne Wang
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Jul 7, 2020·Organic & Biomolecular Chemistry·M Paula DenofrioFranco M Cabrerizo
Apr 3, 2010·Pharmacological Reports : PR·Catrin WernickeHans Rommelspacher
Jul 12, 2013·Organic & Biomolecular Chemistry·Mariana VignoniFranco M Cabrerizo
Dec 29, 2020·European Journal of Pharmacology·Yusuf Oloruntoyin AyipoThenmoly Damodaran
Jul 25, 2020·Journal of the American Chemical Society·Niusha MahmoodiVern L Schramm
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