Kinetic Mechanism for the Model Reaction of NADPH-Cytochrome P450 Oxidoreductase with Cytochrome c

Biochemistry ◽  
1994 ◽  
Vol 33 (40) ◽  
pp. 12012-12021 ◽  
Author(s):  
Daniel S. Sem ◽  
Charles B. Kasper
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome C ◽  
Kinetic Mechanism ◽  
Model Reaction ◽  
P450 Oxidoreductase ◽  
Nadph Cytochrome ◽  
Cytochrome P450 Oxidoreductase

scholarly journals Loss of multiple enzyme activities due to the human genetic variation P284T in NADPH cytochrome P450 oxidoreductase

2019 ◽  
Author(s):  
Shaheena Parween ◽  
Maria Natalia Rojas Velazquez ◽  
Sameer S. Udhane ◽  
Norio Kagawa ◽  
Amit V. Pandey
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome C ◽  
Negative Impact ◽  
Aromatase Activity ◽  
Cytochrome P450 Enzymes ◽  
Ferricyanide Reduction ◽  
P450 Oxidoreductase ◽  
Nadph Cytochrome ◽  
Reduction Activity ◽  
Cytochrome P450 Oxidoreductase

AbstractCytochromes P450 located in the endoplasmic reticulum require NADPH cytochrome P450 oxidoreductase (POR) for their catalytic activities. Mutations in POR cause multiple disorders in humans related to the biosynthesis of steroid hormones and also affect drug-metabolizing cytochrome P450 activities. Here we are reporting the effects of a POR genetic variant P284T which is located in the hinge region of POR that is necessary for the flexibility of domain movements. Human wild-type and P284T mutant of POR, as well as cytochrome P450 proteins, were expressed in bacteria, purified and then reconstituted in liposomes for enzyme kinetic assays. Quality of POR proteins was checked by cytochrome c, ferricyanide and tetrazolium dye reduction assay and measurements flavin content. We found that for the P284T variant of POR the cytochrome c reduction activity was reduced to 47% of the WT and MTT reduction was reduced to only 15% of the WT. No impact on ferricyanide reduction activity was observed, but a severe loss of CYP19A1 (aromatase) activity was observed (9% of WT). In the assays of drug metabolizing cytochrome P450 enzymes, the P284T variant of POR showed 26% activity for CYP2C9, 44% activity for CYP2C19, 23% activity for CYP3A4 and 44% activity in CYP3A5 assays compared to the WT POR. These results indicate a severe effect on several cytochrome P450 activities due to the P284T variation in POR which suggests a negative impact on both the steroid as well as drug metabolism in the individuals carrying this variation.

Drosophila melanogaster NADPH–cytochrome P450 oxidoreductase: pronounced expression in antennae may be related toodorantclearance

Gene ◽  
1997 ◽  
Vol 189 (2) ◽  
pp. 213-219 ◽  
Author(s):  
Bernhard T Hovemann ◽  
Frank Sehlmeyer ◽  
Jochen Malz
Keyword(s):  
Drosophila Melanogaster ◽  
Cytochrome P450 ◽  
P450 Oxidoreductase ◽  
Nadph Cytochrome ◽  
Cytochrome P450 Oxidoreductase

Stable Expression of Human Cytochrome P450 3A4 in Conjunction with Human NADPH-Cytochrome P450 Oxidoreductase in V79 Chinese Hamster Cells

1996 ◽  
Vol 332 (2) ◽  
pp. 295-304 ◽  
Author(s):  
Anneliese Schneider ◽  
Wolfgang A. Schmalix ◽  
Vasanthi Siruguri ◽  
Els M. de Groene ◽  
G.Jean Horbach ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Chinese Hamster ◽  
Stable Expression ◽  
Cytochrome P450 3A4 ◽  
Chinese Hamster Cells ◽  
P450 Oxidoreductase ◽  
Nadph Cytochrome ◽  
Human Cytochrome ◽  
Cytochrome P450 Oxidoreductase

scholarly journals Mechanistic Studies on the Reductive Half-reaction of NADPH-Cytochrome P450 Oxidoreductase

1999 ◽  
Vol 274 (9) ◽  
pp. 5391-5398 ◽  
Author(s):  
Anna L. Shen ◽  
Daniel S. Sem ◽  
Charles B. Kasper
Keyword(s):  
Cytochrome P450 ◽  
Mechanistic Studies ◽  
P450 Oxidoreductase ◽  
Nadph Cytochrome ◽  
Cytochrome P450 Oxidoreductase

Isolation of a New Mouse cDNA Clone: Hybrid Form of Cytochrome P450 2b10 and NADPH-Cytochrome P450 Oxidoreductase

1996 ◽  
Vol 226 (3) ◽  
pp. 900-905 ◽  
Author(s):  
Marie Damon ◽  
Alain Fautrel ◽  
Nathalie Marc ◽  
André Guillouzo ◽  
Laurent Corcos
Keyword(s):  
Cytochrome P450 ◽  
Cdna Clone ◽  
Hybrid Form ◽  
P450 Oxidoreductase ◽  
Nadph Cytochrome ◽  
Mouse Cdna ◽  
Cytochrome P450 Oxidoreductase
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