scholarly journals Lipid-exchange in nanodiscs discloses membrane boundaries of cytochrome-P450 reductase

2018 ◽  
Vol 54 (49) ◽  
pp. 6336-6339 ◽  
Author(s):  
Carlo Barnaba ◽  
Thirupathi Ravula ◽  
Ilce G. Medina-Meza ◽  
Sang-Choul Im ◽  
G. M. Anantharamaiah ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450s ◽  
Cytochrome P450 Reductase ◽  
P450 Reductase ◽  
Lipid Exchange

Lipids are critical for the function of mammalian cytochrome-P450s.

scholarly journals The FMN “140s Loop” of Cytochrome P450 Reductase Controls Electron Transfer to Cytochrome P450

2021 ◽  
Vol 22 (19) ◽  
pp. 10625
Author(s):  
Freeborn Rwere ◽  
Sangchoul Im ◽  
Lucy Waskell
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450s ◽  
Cytochrome P450 Reductase ◽  
Wild Type ◽  
P450 Bm3 ◽  
P450 Reductase ◽  
The Poor ◽  
Cytochrome P450 Bm3 ◽  
Support Activity ◽  
Binding Loop

Cytochrome P450 reductase (CYPOR) provides electrons to all human microsomal cytochrome P450s (cyt P450s). The length and sequence of the “140s” FMN binding loop of CYPOR has been shown to be a key determinant of its redox potential and activity with cyt P450s. Shortening the “140s loop” by deleting glycine-141(ΔGly141) and by engineering a second mutant that mimics flavo-cytochrome P450 BM3 (ΔGly141/Glu142Asn) resulted in mutants that formed an unstable anionic semiquinone. In an attempt to understand the molecular basis of the inability of these mutants to support activity with cyt P450, we expressed, purified, and determined their ability to reduce ferric P450. Our results showed that the ΔGly141 mutant with a very mobile loop only reduced ~7% of cyt P450 with a rate similar to that of the wild type. On the other hand, the more stable loop in the ΔGly141/Glu142Asn mutant allowed for ~55% of the cyt P450 to be reduced ~60% faster than the wild type. Our results reveal that the poor activity of the ΔGly141 mutant is primarily accounted for by its markedly diminished ability to reduce ferric cyt P450. In contrast, the poor activity of the ΔGly141/Glu142Asn mutant is presumably a consequence of the altered structure and mobility of the “140s loop”.

scholarly journals Role of Hepatic Cytochrome P450s in the Pharmacokinetics and Toxicity of Cyclophosphamide: Studies with the Hepatic Cytochrome P450 Reductase Null Mouse

2005 ◽  
Vol 65 (10) ◽  
pp. 4211-4217 ◽  
Author(s):  
Georgia J. Pass ◽  
Dianne Carrie ◽  
Michael Boylan ◽  
Sally Lorimore ◽  
Eric Wright ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450s ◽  
Null Mouse ◽  
Cytochrome P450 Reductase ◽  
P450 Reductase ◽  
Hepatic Cytochrome

Cytochrome P450s and cytochrome P450 reductase in the olfactory organ of the cotton leafwormSpodoptera littoralis

2012 ◽  
Vol 21 (6) ◽  
pp. 568-580 ◽  
Author(s):  
M.-A. Pottier ◽  
F. Bozzolan ◽  
T. Chertemps ◽  
E. Jacquin-Joly ◽  
L. Lalouette ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450s ◽  
Olfactory Organ ◽  
Cytochrome P450 Reductase ◽  
P450 Reductase

scholarly journals RNA interference of NADPH-Cytochrome P450 reductase increases susceptibilities to multiple acaricides in Tetranychus urticae

2019 ◽  
Author(s):  
Adekunle W. Adesanya ◽  
Antonio Cardenas ◽  
Mark D. Lavine ◽  
Doug B. Walsh ◽  
Laura C. Lavine ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Rna Interference ◽  
Tetranychus Urticae ◽  
Cytochrome P450s ◽  
List Type ◽  
Cytochrome P450 Reductase ◽  
Acaricide Resistance ◽  
Nadph Cytochrome ◽  
P450 Reductase ◽  
Nadph Cytochrome P450 Reductase

AbstractThe two-spotted spider mite, Tetranychus urticae, is a polyphagous pest feeding on over 1,100 plant species, including numerous highly valued economic crops. The control of T. urticae largely depends on the use of acaricides, which leads to pervasive development of acaricide resistance. Cytochrome P450-mediated metabolic detoxification is one of the major mechanisms of acaricide resistance in T. urticae. NADPH-cytochrome P450 reductase (CPR) plays as a crucial co-factor protein that donates electron(s) to microsomal cytochrome P450s to complete their catalytic cycle. This study seeks to understand the involvement of CPR in acaricide resistance in urticae. The full-length cDNA sequence of T. urticae’s CPR (TuCPR) was cloned and characterized. TuCPR was ubiquitously transcribed in different life stages of T. urticae and the highest transcription was observed in the nymph and adult stages. TuCPR was constitutively over-expressed in six acaricide resistant populations compared to a susceptible one. TuCPR transcriptional expression was also induced by multiple acaricides in a time-dependent manner. Down-regulation of TuCPR via RNA interference (RNAi) in T. urticae led to reduced enzymatic activities of TuCPR and cytochrome P450s, as well as a significant reduction of resistance to multiple acaricides, abamectin, bifenthrin, and fenpyroximate. The outcome of this study highlights CPR as a potential novel target for eco-friendly control of T. urticae and other related plant-feeding pests.HighlightsPipernoyl butoxide significantly reduced abamectin, bifenthrin, and fenpyroximate resistance in T. urticae populationsT. urticae’s cytochrome P450 reductase (TuCPR) was cloned, sequenced and phylogenetically analyzedAbamectin, bifenthrin and fenpyroximate treatment induced TuCPR gene expressionSilencing of TuCPR in T. urticae caused a reduction in acaricide resistance

Fatty Liver and Impaired Hepatic Metabolism Alters the Congener-Specific Distribution of Polychlorinated Biphenyls (PCBs) in Mice with a Liver-Specific Deletion of Cytochrome P450 Reductase

2020 ◽  
Author(s):  
Xueshu Li ◽  
Chun-Yun Zhang ◽  
Hans-Joachim Lehmler
Keyword(s):  
Cytochrome P450 ◽  
Polychlorinated Biphenyls ◽  
Fatty Liver ◽  
Partition Coefficients ◽  
Hepatic Metabolism ◽  
Gas Chromatography Mass Spectrometry ◽  
Cytochrome P450 Reductase ◽  
P450 Reductase ◽  
Specific Distribution ◽  
Specific Deletion

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that are linked to adverse health outcomes. PCB tissue levels are determinants of PCB toxicity; however, it is unclear how factors, such as an altered metabolism and/or a fatty liver, affect PCB distribution in vivo. We determined the congener-specific disposition of PCBs in mice with a liver specific deletion of cytochrome P450 reductase (KO), a model of fatty liver with impaired hepatic metabolism, and wildtype (WT) mice. Male and female KO and WT mice were exposed orally to Aroclor 1254, a technical PCB mixture. PCBs were quantified in adipose, blood, brain and liver tissues by gas chromatography-mass spectrometry. PCB profiles and levels in tissues were genotype and sex dependent. PCB levels were higher in the liver from KO compared to WT mice. PCB profiles showed clear differences between tissues from the same exposure group. While experimental tissue : blood partition coefficients in KO and WT mice did not follow the trends predicted using a composition-based model, the agreement between experimental and calculated partition coefficients was still reasonable. Thus, a fatty liver and/or an impaired hepatic metabolism alter the distribution of PCBs in mice and the magnitude of the partitioning of PCBs from blood into tissues can be approximated using composition-based models.<br>

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