Site-Directed Mutagenesis of Cytochrome P450 2D6 and 2C19 Enzymes: Expression and Spectral Characterization of Naturally Occurring Allelic Variants

2018 ◽  
Vol 186 (1) ◽  
pp. 132-144 ◽  
Author(s):  
Amelia Nathania Dong ◽  
Yan Pan ◽  
Uma Devi Palanisamy ◽  
Beow Chin Yiap ◽  
Nafees Ahemad ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Spectral Characterization ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Cytochrome P450 2D6 ◽  
Allelic Variants ◽  
Naturally Occurring ◽  
P450 2D6

Molecular Modeling-Guided Site-Directed Mutagenesis of Cytochrome P450 2D6

2007 ◽  
Vol 8 (1) ◽  
pp. 59-77 ◽  
Author(s):  
Chris de Graaf ◽  
Chris Oostenbrink ◽  
Peter J. Keizers ◽  
Barbara A. van Vugt-Lussenburg ◽  
Robert B. van Waterschoot ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Molecular Modeling ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Cytochrome P450 2D6 ◽  
P450 2D6

scholarly journals Characterization of Cytochrome P450 2D6 Alleles Using the Invader™ System

BioTechniques ◽  
2002 ◽  
Vol 32 (6S) ◽  
pp. S34-S43 ◽  
Author(s):  
Matt Neville ◽  
Rebecca Selzer ◽  
Brian Aizenstein ◽  
Megan Maguire ◽  
Kirk Hogan ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 2D6 ◽  
P450 2D6

Functional and structural characterisation of common cytochrome P450 2D6 allelic variants—roles of Pro34 and Thr107 in catalysis and inhibition

2019 ◽  
Vol 392 (8) ◽  
pp. 1015-1029 ◽  
Author(s):  
Amelia Nathania Dong ◽  
Nafees Ahemad ◽  
Yan Pan ◽  
Uma Devi Palanisamy ◽  
Beow Chin Yiap ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 2D6 ◽  
Allelic Variants ◽  
Structural Characterisation ◽  
P450 2D6

scholarly journals Metabolite Profile Resulting from the Activation/Inactivation of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 2-Methyltetrahydro-β-carboline by Oxidative Enzymes

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Tomás Herraiz ◽  
Hugo Guillén ◽  
Juan Galisteo
Keyword(s):  
Cytochrome P450 ◽  
Metabolic Profile ◽  
Metabolite Profile ◽  
Oxidative Enzymes ◽  
Cytochrome P450 2D6 ◽  
Toxicological Effects ◽  
Naturally Occurring ◽  
Aromatic Hydroxylation ◽  
Heme Peroxidases ◽  
P450 2D6

Metabolic enzymes are involved in the activation/deactivation of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyiridine (MPTP) neurotoxin and its naturally occurring analogs 2-methyltetrahydro-β-carbolines. The metabolic profile and biotransformation of these protoxins by three enzymes, monoamine oxidase (MAO), cytochrome P450, and heme peroxidases (myeloperoxidase and lactoperoxidase), were investigated and compared. The metabolite profile differed among the enzymes investigated. MAO and heme peroxidases activated these substances to toxic pyridinium andβ-carbolinium species. MAO catalyzed the oxidation of MPTP to 1-methyl-4-phenyl-2,3-dihydropyridinium cation (MPDP+), whereas heme peroxidases catalyzed the oxidation of MPDP+to 1-methyl-4-phenylpyridinium (MPP+) and of 2-methyltetrahydro-β-carboline to 2-methyl-3,4-dihydro-β-carbolinium cation (2-Me-3,4-DHβC+). These substances were inactivated by cytochrome P450 2D6 throughN-demethylation and aromatic hydroxylation (MPTP) and aromatic hydroxylation (2-methyltetrahydro-β-carboline). In conclusion, the toxicological effects of these protoxins might result from a balance between the rate of their activation to toxic products (i.e.,N-methylpyridinium-MPP+and MPDP+- andN-methyl-β-carbolinium—βC+—) by MAO and heme peroxidases and the rate of inactivation (i.e.,N-demethylation, aromatic hydroxylation) by cytochrome P450 2D6.

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