Dissociation Constants of Cytochrome P450 2C9/Cytochrome P450 Reductase Complexes in a Lipid Bilayer Membrane Depend on NADPH: A Single-Protein Tracking Study

2017 ◽  
Vol 139 (49) ◽  
pp. 17923-17934 ◽  
Author(s):  
Carlo Barnaba ◽  
Evan Taylor ◽  
James A. Brozik
Keyword(s):  
Cytochrome P450 ◽  
Lipid Bilayer ◽  
Dissociation Constants ◽  
Bilayer Membrane ◽  
Lipid Bilayer Membrane ◽  
Cytochrome P450 Reductase ◽  
Cytochrome P450 2C9 ◽  
P450 Reductase ◽  
Single Protein ◽  
Protein Tracking

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>

scholarly journals Transmembrane signal transduction by cofactor transport

2021 ◽  
Author(s):  
Istvan Kocsis ◽  
Yudi Ding ◽  
Nicholas H. Williams ◽  
Christopher A. Hunter
Keyword(s):  
Signal Transduction ◽  
Lipid Bilayer ◽  
Metal Ion ◽  
Bilayer Membrane ◽  
Ester Hydrolysis ◽  
Lipid Bilayer Membrane ◽  
Metal Ion Cofactors

Synthetic transducers transport externally added metal ion cofactors across the lipid bilayer membrane of vesicles to trigger catalysis of ester hydrolysis in the inner compartment. Signal transduction activity is modulated by hydrazone formation.

scholarly journals Protein Sensing Device with Multi-Recognition Ability Composed of Self-Organized Glycopeptide Bundle

2020 ◽  
Vol 22 (1) ◽  
pp. 366
Author(s):  
Mao Arai ◽  
Tomohiro Miura ◽  
Yuriko Ito ◽  
Takatoshi Kinoshita ◽  
Masahiro Higuchi
Keyword(s):  
Binding Site ◽  
Lipid Bilayer ◽  
Structural Changes ◽  
Bilayer Membrane ◽  
Lipid Bilayer Membrane ◽  
Target Protein ◽  
Self Organization ◽  
Specific Response ◽  
Target Proteins ◽  
Recognition Ability

We designed and synthesized amphiphilic glycopeptides with glucose or galactose at the C-terminals. We observed the protein-induced structural changes of the amphiphilic glycopeptide assembly in the lipid bilayer membrane using transmission electron microscopy (TEM) and Fourier transform infrared reflection-absorption spectra (FTIR-RAS) measurements. The glycopeptides re-arranged to form a bundle that acted as an ion channel due to the interaction among the target protein and the terminal sugar groups of the glycopeptides. The bundle in the lipid bilayer membrane was fixed on a gold-deposited quartz crystal microbalance (QCM) electrode by the membrane fusion method. The protein-induced re-arrangement of the terminal sugar groups formed a binding site that acted as a receptor, and the re-binding of the target protein to the binding site induced the closing of the channel. We monitored the detection of target proteins by the changes of the electrochemical properties of the membrane. The response current of the membrane induced by the target protein recognition was expressed by an equivalent circuit consisting of resistors and capacitors when a triangular voltage was applied. We used peanut lectin (PNA) and concanavalin A (ConA) as target proteins. The sensing membrane induced by PNA shows the specific response to PNA, and the ConA-induced membrane responded selectively to ConA. Furthermore, PNA-induced sensing membranes showed relatively low recognition ability for lectin from Ricinus Agglutinin (RCA120) and mushroom lectin (ABA), which have galactose binding sites. The protein-induced self-organization formed the spatial arrangement of the sugar chains specific to the binding site of the target protein. These findings demonstrate the possibility of fabricating a sensing device with multi-recognition ability that can recognize proteins even if the structure is unknown, by the protein-induced self-organization process.

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