ubiquinone and 1-palmitoyl-2-oleoylphosphatidylcholine

Ferroptosis is a recently discovered iron-dependent form of non-apoptotic cell death caused by the accumulation of membrane lipid peroxidation products, which is involved in various pathological conditions of the brain, kidney, liver and heart. A potent spiroquinoxalinamine derivative named liproxstatin-1 is discovered by high-throughput screening, which is able to suppress ferroptosis via lipid peroxide scavenging in vivo. Thus, molecular simulations, density functional theory (DFT) and variational transition-state theory with a small-curvature tunneling (SCT) coefficient are utilized to elucidate the detailed mechanisms of inactivation of a lipid peroxide radical by liproxstatin-1. H-atom abstracted from liproxstatin-1 by a CH

Topics: Free Radicals; Iron; Kinetics; Lipid Peroxides; Molecular Dynamics Simulation; Phosphatidylcholines; Quantum Theory; Quinoxalines; Spiro Compounds; Structure-Activity Relationship; Thermodynamics; Ubiquinone

Buildup of hydrogen sulfide (H

Topics: Apolipoprotein A-I; Biocatalysis; Cysteine; Electron Transport; Enzymes, Immobilized; Glutathione; Humans; Hydrogen Sulfide; Kinetics; Models, Molecular; Nanoparticles; Oxidation-Reduction; Oxidoreductases Acting on Sulfur Group Donors; Peptide Fragments; Phosphatidylcholines; Recombinant Proteins; Solubility; Ubiquinone

Ubiquinone-10 is mostly known for its role as an electron and proton carrier in aerobic cellular respiration and its function as a powerful antioxidant. Accumulating evidence suggest, however, that this well studied membrane component could have several other important functions in living cells. The current study reports on a previously undocumented ability of ubiquinone-10 to modulate the mechanical strength and permeability of lipid membranes. Investigations of DPH fluorescence anisotropy, spontaneous and surfactant induced leakage of carboxyfluorescein, and interactions with hydrophobic and hydrophilic surfaces were used to probe the effects caused by inclusion of ubiquinone-10 in the membrane of phospholipid liposomes. The results show that ubiquinone in concentrations as low as 2 mol% increases the lipid packing order and condenses the membrane. The altered physicochemical properties result in a slower rate of release of hydrophilic components, and render the membrane more resistant towards rupture. As judged from comparative experiments using the polyisoprenoid alcohol solanesol, the quinone moiety is essential for the membrane stabilizing effects to occur. Our findings imply that the influence of ubiquinone-10 on the permeability and mechanical properties of phospholipid membranes is similar to that of cholesterol. The reported data indicate, however, that the molecular mechanisms are different in the two cases.

Topics: Hydrophobic and Hydrophilic Interactions; Liposomes; Membrane Fluidity; Phosphatidylcholines; Porosity; Surface Properties; Tensile Strength; Ubiquinone; Viscosity

It is reported that the reduction of ubiquinone incorporated into supported lipid bilayers and into immobilized liposome layers on gold electrodes is kinetically and thermodynamically enhanced by the presence of acetylcholine and tetrabutylammonium (TBA(+)) in solution. The reduction peak and the mid-peak potentials of the redox reactions, determined by cyclic voltammetry, are displaced towards more positive potentials by approximately 500 and 250mV, respectively, in the case of TBA(+); and by approximately 750 and 530mV, respectively, in the case of acetylcholine. The intensity of the signal varies with the cation concentration, allowing for quantitative determinations in the millimolar range. It is proposed that the enhanced reduction of ubiquinone arises from the formation of tetraalkylammonium cation-ubiquinone radical anion ion-pairs. Electrochemical quartz crystal microbalance with dissipation monitoring (EQCM-D) measurements confirmed that the potential shift and the intensity of the redox signal are coupled with the adsorption of the tetraalkylammonium cations on the lipid membrane. The Langmuir adsorption equilibrium constant (K) of TBA(+) on lipid membranes at physiological pH is determined. In supported lipid bilayers K=440.7±160M(-1), while in an immobilized liposome layer K=35.53±3.53M(-1).

Topics: Acetylcholine; Biosensing Techniques; Cell Membrane; Electrochemistry; Electrodes; Gold; Lipid Bilayers; Liposomes; Phosphatidylcholines; Quaternary Ammonium Compounds; Ubiquinone

There are tremendous drug candidates that suffer from insolubility in water. In the present study, it is shown that Coenzyme Q10 (CoQ10), a model water-insoluble compound, can be nanoparticulated into a water-soluble form using apolipoprotein A-I (apoA-I). Similar to the way that apoA-I forms nascent discoidal high density lipoprotein (ndHDL) particles by bordering acyl chain tails of phospholipids, CoQ10 could be enclosed into the circle of a disk made of apoA-Is. The resulting nanostructure of CoQ10 and apoA-I was water-soluble with a size of approximately 12 nm in diameter and was physically more robust than liposome. We expect that the strategy suggested in this study can be exploited to assemble nano-sized, water-soluble structures of various water-insoluble drug candidates.

Topics: Apolipoprotein A-I; Lipoproteins, HDL; Nanoparticles; Particle Size; Phosphatidylcholines; Solubility; Ubiquinone; Water

In the last decade, the structures of many components of the photosynthetic apparatus of purple bacteria, as well as the mutual organization of these components within the purple membrane, were resolved. One key question that emerged concerned the assembly of the core complex consisting of the reaction center (RC) and the light-harvesting 1 (LH1) complex. In some species, like Rhodobacter sphaeroides, the ring-shaped LH1 complex was found to be open, whereas other species, like Rhodospirillum rubrum, have a closed ring surrounding the reaction center. This poses the question of how the ubiquinone molecule that transports electrons and protons from the RC to the cytochrome bc(1) complex overcomes the apparent barrier of the LH1 ring. In this study, we investigated how, in the case of a closed LH1 ring, the ubiquinone molecule diffuses through the LH1 ring. For this purpose, the LH1 structure of R. rubrum was modeled and the potential of mean force along the diffusion pathway through the LH1 was determined by steered molecular-dynamics simulations. The potential was reconstructed using the fluctuation theorem in combination with the stiff spring approximation. An upper limit for the mean first-passage time for diffusion of ubiquinone through the LH1 ring, based on a worst-case scenario potential, was calculated as approximately 8 x 10(-3) s, which is still in agreement with known turnover rates of RC and RC-LH1 complexes in the range of approximately 1000 Hz.

Topics: Biological Transport; Computer Simulation; Electrons; Light-Harvesting Protein Complexes; Lipid Bilayers; Models, Chemical; Models, Molecular; Models, Statistical; Molecular Conformation; Phosphatidylcholines; Protein Conformation; Protons; Rhodospirillum rubrum; Ubiquinone