scholarly journals Structural and Kinetic Studies of Novel Cytochrome P450 Small-Alkane Hydroxylases

2012 ◽  
Author(s):  
Frances H. Arnold
Keyword(s):  
Cytochrome P450 ◽  
Kinetic Studies ◽  
Alkane Hydroxylases

Thermodynamic and Kinetic Studies on the Binding of Nitric Oxide to a New Enzyme Mimic of Cytochrome P450

2006 ◽  
Vol 128 (41) ◽  
pp. 13611-13624 ◽  
Author(s):  
Alicja Franke ◽  
Natalya Hessenauer-Ilicheva ◽  
Dominik Meyer ◽  
Grażyna Stochel ◽  
Wolf-D. Woggon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cytochrome P450 ◽  
Kinetic Studies ◽  
Enzyme Mimic

scholarly journals Cytochrome P450 Alkane Hydroxylases of the CYP153 Family Are Common in Alkane-Degrading Eubacteria Lacking Integral Membrane Alkane Hydroxylases

2006 ◽  
Vol 72 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Jan B. van Beilen ◽  
Enrico G. Funhoff ◽  
Alexander van Loon ◽  
Andrea Just ◽  
Leo Kaysser ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Pseudomonas Putida ◽  
Chain Length ◽  
Nonheme Iron ◽  
Cytochrome P450 Enzymes ◽  
Medium Chain ◽  
Ferredoxin Reductase ◽  
Medium Chain Length ◽  
Reductase Gene ◽  
Alkane Hydroxylases

ABSTRACT Several strains that grow on medium-chain-length alkanes and catalyze interesting hydroxylation and epoxidation reactions do not possess integral membrane nonheme iron alkane hydroxylases. Using PCR, we show that most of these strains possess enzymes related to CYP153A1 and CYP153A6, cytochrome P450 enzymes that were characterized as alkane hydroxylases. A vector for the polycistronic coexpression of individual CYP153 genes with a ferredoxin gene and a ferredoxin reductase gene was constructed. Seven of the 11 CYP153 genes tested allowed Pseudomonas putida GPo12 recombinants to grow well on alkanes, providing evidence that the newly cloned P450s are indeed alkane hydroxylases.

scholarly journals Spectra and Kinetic Studies of the Compound I Derivative of Cytochrome P450 119

2008 ◽  
Vol 130 (40) ◽  
pp. 13310-13320 ◽  
Author(s):  
Xin Sheng ◽  
John H. Horner ◽  
Martin Newcomb
Keyword(s):  
Cytochrome P450 ◽  
Kinetic Studies ◽  
Compound I

Interflavin electron transfer in human cytochrome P450 reductase is enhanced by coenzyme binding. Relaxation kinetic studies with coenzyme analogues

2003 ◽  
Vol 270 (12) ◽  
pp. 2612-2621 ◽  
Author(s):  
Aldo Gutierrez ◽  
Andrew W. Munro ◽  
Alex Grunau ◽  
C. Roland Wolf ◽  
Nigel S. Scrutton ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Cytochrome P450 ◽  
Kinetic Studies ◽  
Cytochrome P450 Reductase ◽  
Relaxation Kinetic ◽  
Coenzyme Binding ◽  
P450 Reductase ◽  
Human Cytochrome

In vitro Inhibitory Effects of Isofraxidin on Human Liver Cytochrome P450 Enzymes

Pharmacology ◽  
2018 ◽  
Vol 103 (3-4) ◽  
pp. 120-127 ◽  
Author(s):  
Xiaoli Song ◽  
Gang Dong ◽  
Yun Zhou
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Kinetic Studies ◽  
Competitive Inhibitor ◽  
Cytochrome P450 Enzymes ◽  
Inhibitory Effects ◽  
Liver Cytochrome ◽  
Cyp Isoforms

Isofraxidin is a Coumarin compound widely distributed in plants, such as the Umbelliferae or Chloranthaceae, and it possesses numerous pharmacological activities. However, whether isofraxidin affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. In this study, the inhibitory effects of isofraxidin on the 8 human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using human liver microsomes. The results showed that isofraxidin inhibited the activity of CYP1A2, 3A4, and 2E1, with IC50 values of 23.01, 15.49, and 15.98 µmol/L, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that isofraxidin was not only a noncompetitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP1A2 and 2E1, with Ki values of 7.91, 10.14, and 9.30 µmol/L, respectively. In addition, isofraxidin is a time-dependent inhibitor for CYP3A4 with Kinact/KI value of 0.047/12.33 µmol/L–1min–1. The in vitro studies of isofraxidin with CYP isoforms indicate that isofraxidin has the potential to cause pharmacokinetic drug interactions with other coadministered drugs metabolized by ­CYP1A2, 3A4, and 2E1. Further clinical studies are needed to evaluate the significance of this interaction.

In vitrometabolism of a novel antithrombotic compound, S002-333, and its enantiomers: quantitative cytochrome P450 phenotyping, metabolic profiling and enzyme kinetic studies

Xenobiotica ◽  
2013 ◽  
Vol 44 (4) ◽  
pp. 295-308 ◽  
Author(s):  
Amrita Saxena ◽  
Girish K. Jain ◽  
Hefazat H. Siddiqui ◽  
Shom S. Bhunia ◽  
Anil K. Saxena ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Metabolic Profiling ◽  
Kinetic Studies ◽  
Enzyme Kinetic

Effects of cytochrome P450 inhibitors and of steroid hormones on the formation of 7-hydroxylated metabolites of pregnenolone in mouse brain microsomes

1997 ◽  
Vol 155 (2) ◽  
pp. 343-350 ◽  
Author(s):  
J Doostzadeh ◽  
R Morfin
Keyword(s):  
Cytochrome P450 ◽  
Mouse Brain ◽  
Kinetic Studies ◽  
Competitive Inhibitor ◽  
Gas Chromatography Mass Spectrometry ◽  
Brain Microsomes ◽  
Hormone Effects ◽  
Cyp 1A2 ◽  
Layer Chromatography ◽  
P450 Inhibitors

Hydroxylations of pregnenolone (PREG) at the 7 alpha- and 7 beta-positions have been reported in numerous murine tissues and organs and responsible cytochrome P450 (CYP) species await identification. Using thin layer chromatography and gas chromatography-mass spectrometry, we report identification of 7 alpha-hydroxy-PREG and 7 beta-hydroxy-PREG metabolites produced in mouse brain microsome digests and kinetic studies of their production with apparent KM values of 0.5 +/- 0.1 microM and 5.1 +/- 0.6 microM for 7 alpha- and 7 beta-hydroxylation respectively. Investigation of CYP inhibitors and of steroid hormone effects on both 7 alpha- and 7 beta-hydroxylations of PREG showed that: (i) different CYP were involved in 7 alpha- and 7 beta-hydroxylation of PREG because solely 7 alpha-hydroxylation was extensively inhibited by metyrapone, alpha-naphthoflavone, ketoconazole and 3 beta-hydroxysteroids, (ii) CYP 1A2, 2D6, 2B1 and 2B11 were not responsible for 7 alpha- and 7 beta-hydroxylation of PREG because respective specific inhibitors furafylline, quinidine and chloramphenicol triggered no inhibition, (iii) CYP 1A1 was responsible for only part of the 7 beta-hydroxylation of PREG because use of alpha-naphthoflavone, which inhibits specifically CYP 1A1, did not suppress entirely 7 beta-hydroxylation, while ketoconazole, metyrapone and antipyrine, which do not inhibit CYP 1A1, decreased part of the 7 beta-hydroxylation, (iv) 7 alpha-hydroxylation of PREG may be shared with other 3 beta-hydroxysteroids such as isoandrosterone and 5-androstene-3 beta,17 beta-diol which were strong inhibitors, but not with dehydroepiandrosterone which was a non-competitive inhibitor as weak as 3-oxosteroids, and (v) 7 beta-hydroxylation of PREG was not markedly changed by other steroids. Taken together, these findings will be of use for identification of the CYP species responsible for 7 alpha- and 7 beta-hydroxylation of PREG and for studies of their activities in brain.

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