Biosynthesis of Himastatin: Assembly Line and Characterization of Three Cytochrome P450 Enzymes Involved in the Post-tailoring Oxidative Steps

2011 ◽  
Vol 123 (34) ◽  
pp. 7943-7948 ◽  
Author(s):  
Junying Ma ◽  
Zhongwen Wang ◽  
Hongbo Huang ◽  
Minghe Luo ◽  
Dianguang Zuo ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Assembly Line ◽  
Cytochrome P450 Enzymes

Biosynthesis of Himastatin: Assembly Line and Characterization of Three Cytochrome P450 Enzymes Involved in the Post-tailoring Oxidative Steps

2011 ◽  
Vol 50 (34) ◽  
pp. 7797-7802 ◽  
Author(s):  
Junying Ma ◽  
Zhongwen Wang ◽  
Hongbo Huang ◽  
Minghe Luo ◽  
Dianguang Zuo ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Assembly Line ◽  
Cytochrome P450 Enzymes

Characterization of Diuron N-Demethylation by Mammalian Hepatic Microsomes and cDNA-Expressed Human Cytochrome P450 Enzymes

2007 ◽  
Vol 35 (9) ◽  
pp. 1634-1641 ◽  
Author(s):  
Khaled Abass ◽  
Petri Reponen ◽  
Miia Turpeinen ◽  
Jorma Jalonen ◽  
Olavi Pelkonen
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzymes ◽  
Hepatic Microsomes ◽  
Human Cytochrome

scholarly journals Characterization of O-demethylations and Aromatic Hydroxylations Mediated by Cytochromes P450 in the Metabolism of Flavonoid Aglycons

2019 ◽  
Vol 92 (1) ◽  
pp. 115-123 ◽  
Author(s):  
Goran Benković ◽  
Hrvoje Rimac ◽  
Željan Maleš ◽  
Siniša Tomić ◽  
Zoran Lončar ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Cytochromes P450 ◽  
Liver Microsomes ◽  
Cytochrome P450 Enzymes ◽  
Uv Detector ◽  
Aromatic Hydroxylation ◽  
Metabolism Of Xenobiotics ◽  
Kinetics Of

One of the most important groups of metabolic enzymes is cytochrome P450 superfamily. These enzymes are important in terms of the catalytic diversity and the large number of xenobiotics that are detoxified or activated by converting to reactive metabolites. Flavonoids are xenobiotics to which humans are exposed through diet. Data on their oxidative metabolism mediated by cytochromes P450 are limited. The aim of this study was to determine the enzymatic kinetics of O-demethylation and aromatic hydroxylation of flavonoid aglycons on recombinant cytochrome P450 enzymes and human liver microsomes systems. The study was performed on ten flavonoids, namely 3,7-dihydroxyflavone, 7-hydroxyflavone, acacetin, apigenin, flavone, galangin, kaempferol, naringenin, sakuranetin, and tangeretin using liquid chromatography coupled with mass spectrometry and UV detector. Most relevant enzyme involved in metabolism of flavonoid aglycons is CYP1A2, and its catalytic effectiveness ranges from 0.5 to 2.9 × 106 M–1 min–1. Having in mind high expression and involvement of CYP1A2 in metabolism of xenobiotics including drugs, and its intraindividual differences in expression and activity, potential of drug-flavonoid competitive interactions/inhibitions should be considered when consuming dietary supplement and foods rich in flavonoids.

scholarly journals In Vitro Characterization of Ertugliflozin Metabolism by UDP-Glucuronosyltransferase and Cytochrome P450 Enzymes

2020 ◽  
Vol 48 (12) ◽  
pp. 1350-1363
Author(s):  
Kimberly Lapham ◽  
Ernesto Callegari ◽  
Julie Cianfrogna ◽  
Jian Lin ◽  
Mark Niosi ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzymes ◽  
In Vitro Characterization ◽  
Udp Glucuronosyltransferase

Characterization of human cytochrome P450 enzymes involved in thein vitro metabolism of perospirone

2005 ◽  
Vol 26 (2) ◽  
pp. 59-65 ◽  
Author(s):  
Atsushi Kitamura ◽  
Yoshiko Mizuno ◽  
Kiyoshi Natsui ◽  
Masashi Yabuki ◽  
Setsuko Komuro ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzymes ◽  
Human Cytochrome

scholarly journals Characterization of Medicago truncatula (barrel medic) hydroperoxide lyase (CYP74C3), a water-soluble detergent-free cytochrome P450 monomer whose biological activity is defined by monomer–micelle association

2006 ◽  
Vol 395 (3) ◽  
pp. 641-652 ◽  
Author(s):  
Richard K. Hughes ◽  
Eric J. Belfield ◽  
Mylrajan Muthusamay ◽  
Anuja Khan ◽  
Arthur Rowe ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cytochrome P450 ◽  
Medicago Truncatula ◽  
Water Soluble ◽  
Hydroperoxide Lyase ◽  
Cytochrome P450 Enzyme ◽  
Cytochrome P450 Enzymes ◽  
P450 Enzyme ◽  
Detergent Micelles

We describe the detailed biochemical characterization of CYP74C3 (cytochrome P450 subfamily 74C3), a recombinant plant cytochrome P450 enzyme with HPL (hydroperoxide lyase) activity from Medicago truncatula (barrel medic). Steady-state kinetic parameters, substrate and product specificities, RZ (Reinheitszahl or purity index), molar absorption coefficient, haem content, and new ligands for an HPL are reported. We show on the basis of gel filtration, sedimentation velocity (sedimentation coefficient distribution) and sedimentation equilibrium (molecular mass) analyses that CYP74C3 has low enzyme activity as a detergent-free, water-soluble, monomer. The enzyme activity can be completely restored by re-activation with detergent micelles, but not detergent monomers. Corresponding changes in the spin state equilibrium, and probably co-ordination of the haem iron, are novel for cytochrome P450 enzymes and suggest that detergent micelles have a subtle effect on protein conformation, rather than substrate presentation, which is sufficient to improve substrate binding and catalytic-centre activity by an order of magnitude. The kcat/Km of up to 1.6×108 M−1·s−1 is among the highest recorded, which is remarkable for an enzyme whose reaction mechanism involves the scission of a C–C bond. We carried out both kinetic and biophysical studies to demonstrate that this effect is a result of the formation of a complex between a protein monomer and a single detergent micelle. Association with a detergent micelle rather than oligomeric state represents a new mechanism of activation for membrane-associated cytochrome P450 enzymes. Highly concentrated and monodispersed samples of detergent-free CYP74C3 protein may be well suited for the purposes of crystallization and structural resolution of the first plant cytochrome P450 enzyme.

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