Active oxygen chemistry within the liposomal bilayer (2025)

On the interaction of ubiquinones with phospholipid bilayers

FEBS Letters, 1981

Tocopherol Activity Correlates with Its Location in a Membrane: A New Perspective on the Antioxidant Vitamin E

Journal of the American Chemical Society, 2013

We show evidence of an antioxidant mechanism for vitamin E which correlates strongly with its physical location in a model lipid bilayer. These data address the overlooked problem of the physical distance between the vitamin's reducing hydrogen and lipid acyl chain radicals. Our combined data from neutron diffraction, NMR, and UV spectroscopy experiments all suggest that reduction of reactive oxygen species and lipid radicals occurs specifically at the membrane's hydrophobic−hydrophilic interface. The latter is possible when the acyl chain "snorkels" to the interface from the hydrocarbon matrix. Moreover, not all model lipids are equal in this regard, as indicated by the small differences in vitamin's location. The present result is a clear example of the importance of lipid diversity in controlling the dynamic structural properties of biological membranes. Importantly, our results suggest that measurements of aToc oxidation kinetics, and its products, should be revisited by taking into consideration the physical properties of the membrane in which the vitamin resides.

Location of ubiquinone homologues in liposome membranes studied by fluorescence anisotropy of diphenyl-hexatriene and trimethylammonium-diphenyl-hexatriene

Chemistry and Physics of Lipids, 1996

The measurements of diphenyl-hexatriene (DPH) and trimethylammonium-diphenyl-hexatriene (TMA-DPH) fluorescence anisotropy in dipalmitoylphosphatidylcholine (DPPC) and egg yolk lecithin (EYL) liposomes containing different concentrations of various ubiquinone (UQ) homologues have been performed. UQ-4 induced the highest DPH anisotropy increase in DPPC liposomes, whereas for higher UQ homologues the anisotropy was lowered with the increase of UQ side-chain length. These differences were less pronounced in EYL liposomes. It was concluded that at a higher content in the membranes (3-4 mol%), the short-chain ubiquinones are arranged parallel to lipid fatty acid chains, whereas long-chain homologues are progressively removed from the lipid acyl chains into the midplane region of the membrane. At the lower (1-2 mol%) concentrations, long-chain quinones seem to be evenly distributed within the membrane, especially in EYL membranes. UQ-10 in EYL liposomes perturbed TMA-DPH to a similar extend as the short-chain ubiquinones indicating that UQ-10 penetrates the interface regions of the membrane where its redox reactions occur. The localization and physical state of UQ-10 in native membranes is discussed.

Antioxidant action of ubiquinol homologues with different isoprenoid chain length in biomembranes

Free Radical Biology and Medicine, 1990

Ubiquinones (CoQn) are intrinsic lipid components of many membranes Besides their role in electrontransfer reactions they may act as free radical scavengers, yet their antlox~dant function has received relatively little study The efficiency of ubiquinols of varying lsoprenold chain length (from Q0 to Q~0) in preventmg (Fe 2÷ + ascorbate)-dependent or (Fe 2÷ + NADPH)-dependent lipid peroxidatlon was investigated in rat liver mlcrosomes and brain synaptosomes and mitochondria Ublqumols, the reduced forms of CoQn, possess much greater antloxldant activity than the oxidized ublqumone forms In homogenous solution the ra&cal scavenging activity of ublqumol homologues does not depend on the length of their isoprenold chain However in membranes ublqulnols with short lsoprenold chains (Q~-Q4) are much more potent mhibitors of lipid peroxldatlon than the longer chain homologues (Q~-Q~0) It is found that i) the inhibitory action, that is, antloxldant efficiency of shortchain ublqulnols decreases m order Q~ > Q2 > Q3 > Q4, n) the antloxldant efficiency of long-chain ublqulnols is only shghtly dependent on their concentrations m the order Q5 > Q6 > Q7 > Q8 > Q9 > Q~0 and m) the antlOxldant efficiency of Q0 is markedly less than that of other homologues Interaction of ublqumols with oxygen radicals was followed by their effects on luminol-activated chemiluminescence Ublqulnols Qt-Q, at 0 l mM completely inhibit the luminol-activated NADPH-dependent chemtlumlnescent response of mlcrorosomes, while homologues Q6-Q~0 exert no effect In contrast to ublquinol Q~0 (ubiqumone Q~0) ubiqumone Q~ synergistically enhances NADPH-dependent regeneration of endogenous vitamin E in microsomes thus providing for higher antioxidant protection against lipid peroxidation The differences in the antloxidant potency of ubiqumols in membranes are suggested to result from differences in partmoning into membranes, lntramembrane moblhty and non-uniform dlstribuuon of ublqulnols resulting in differing efficiency of interaction with oxygen and hpld radicals as well as different efficiency of ublqulnols in regeneration of endogenous vitamin E

The physical state of ubiquinone-10, in pure form and incorporated into phospholipid bilayers. A Fourier-transform infrared spectroscopic study

European Journal of Biochemistry, 1992

Long-chain quinones are essential components of both bacterial and eukaryotic respiratory chains, and some of the main unsolved questions on energy transduction in membranes are complicated by the lack of consistent information on the physical state of the quinones in membrane bilayers. We have recorded, at various temperatures and under different conditions, the infrared spectra of ubiquinone-10 (the main species in mitochondria) and several analogues. The C = 0 stretching Vibration band located at 1663 -1670 cm-I has been identified as the most sensitive one to phase and environmental changes. Three distinct phases have been characterized in which pure ubiquinone-10 may exist: crystalline (LC,), isotropic liquid (IL) and liquid crystalline (L& The only allowed thermotropic transitions are LCl --t IL, IL + L, and L, -+ LC1. Our investigations with pure quinones provide a simpler and more detailed description of their phase changes than any of the previous studies and shed light on their behaviour in membranes. When incorporated into phospholipid bilayers, ubiquinone-10 appears to be removed from the aqueous environment and is found to exist, in the 4-70°C range, in an isotropic liquid phase, in the form of small aggregates.

Electron spin resonance study of the role of vitamin E and vitamin C in the inhibition of fatty acid oxidation in a model membrane

Chemistry and Physics of Lipids, 1983

The neutral a-tocopheroxyl radicals, generated in monolayers on silica gel containing a-tocopherol and partly autoxidised methyl linoleate at 90°C, were detected and identified by ESR spectroscopy. Addition of ascorbic acid to the monolayer resulted in the complete quenching of the a-tocopheroxyl radical spectrum. This lends support to the view that ascorbate transfers hydrogen to a-tocopheroxyl radicals thus regenerating a-tocopherol.

Superoxide organic chemistry within the liposomal bilayer, part II: a correlation between location and chemistry

Free Radical Biology and Medicine, 2002

Coumarin ester derivatives 1, substituted at C-4 and/or C-12 with alkyl chains, were synthesized and intercalated within DMPC liposomal bilayers. By correlating the 13 C chemical shift with medium polarity [E T (30)], the relative location of these substrates within the liposomal bilayer was determined. The length of the alkyl chain substituents clearly influences the lipophilicity of the substrates and their location and orientation within the liposome: Superoxide readily saponifies the C-12 esteric linkage of 1, when this reaction site lies in a polar region of the liposome (E T (30) Ͼ 45 kcal/mol), to give the corresponding 7-hydroxy coumarin derivatives 2. However, when C-12 lies deeper and is hence less available to O 2 •Ϫ , the lactonic carbon C-2, which lies in a shallower region (E T (30) ϭ 43-49), is the preferred site for superoxide-mediated cleavage. When coumarin 1 is disubstituted with long chains at both C-12 and C-4, these derivatives lie deep within the bilayer and react only slowly with O 2 •Ϫ . These results indicate there is indeed a correlation between location within the bilayer and substrate reactivity. Contrary to the suggestion of Dix and Aikens (Chem. Res. Toxicol. 6:2-18; 1993) superoxide can penetrate deep within the liposomal bilayer. Nevertheless, its concentration drops precipitously (to ϳ16% of what it is near the interface) below E T values of 38, thereby precluding substantial reaction with many highly lipophilic substrates. This work also confirms the findings of others that reactions of small oxy-radicals occur within cellular membranes and appear to be of significant biological importance.

Influence of the redox state of ubiquinones and plastoquinones on the order of lipid bilayers studied by fluorescence anisotropy of diphenylhexatriene and trimethylammonium diphenylhexatriene

1996

The measurements of diphenylhexatriene (DPH) and trimethylammonium diphenylhexatriene (TMA-DPH) fluorescence anisotropy in egg yolk lecithin (EYL) and of DPH anisotropy in dipalmitoylphosphatidylcholine (DPPC) liposomes containing different concentrations of oxidized and reduced ubiquinone (UQ) and plastoquinone (PQ) homologues have been performed. All the oxidized UQ homologues strongly induced ordering of EYL membrane structure, whereas in DPPC liposomes, above the phase transition temperature, the most pronounced effect showed UQ-4. PQ-2 and PQ-9 were less effective than the corresponding ubiquinones in this respect. The reduced forms of UQ and PQ homologues increased the order of membrane lipids to a smaller extent than the corresponding quinones both in the interior of the membrane and closer to its surface. Nevertheless, the investigated prenylquinols showed stronger increase in the membrane order than cr-tocopherol or a-tocopherol acetate, which could be connected with binding of prenylquinol head groups to phospholipid molecules by hydrogen bonds. The strong ordering influence of ubiquinones on the membrane structure was attributed to methoxyl groups of the UQ quinone rings.

Fluorescence Studies of the Interactions of Ubiquinol-10 with Liposomes

Photochemistry and Photobiology, 2007

Ubiquinone-10 plays a central role in energy production and its reduced form, ubiquinol-10 is also capable of acting as a potent radical scavenging antioxidant against membrane lipid peroxidation. Efficiency of this protection depends mostly on its localization in lipid bilayer. The intrinsic fluorescence of ubiquinol-10 and of the exogenous probe, Laurdan, has been used to determine the location of ubiquinol-10 in unilamellar liposomes of egg phosphatidylcholine (EggPC) and dimyristoyl phosphatidylcholine. Laurdan fluorescence moiety is positioned at the hydrophilic-hydrophobic interface of the phospholipid bilayer and its parameters reflect the membrane polarity and microheterogeneity, which we have used to explore the coexistence of microdomains with distinct physical properties. In liquid-crystalline bilayers ubiquinol has a short fluorescence lifetime (0.4 ns) and a high steady-state anisotropy. In a concentration-dependent manner, ubiquinol-10 influences the Laurdan excitation, emission and generalized polarization measurements. In EggPC liposomes ubiquinol-10 induces a decrease in membrane water mobility near the probe, while in dimyristoyl liposomes a decrease in the membrane water content was found. Moreover the presence of ubiquinol results in the formation of coexisting phospholipid domains of gel and liquid-crystalline phases. The results indicate that ubiquinol-10 molecules are mainly located at the polar-lipid interface, inducing changes in the physico-chemical properties of the bilayer microenvironment.

Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations

Proceedings of the National Academy of Sciences, 1990

It is well known that ubiquinone-10 (coenzyme Q10, ubiquinone 50) acts as an electron carrier of the respiratory chain in mitochondria. In this paper we show that ubiquinol-10, the reduced form of ubiquinone-10, also efficiently scavenges free radicals generated chemically within liposomal membranes. Ubiquinol-10 is about as effective in preventing peroxidative damage to lipids as alpha-tocopherol, which is considered the best lipid-soluble antioxidant in humans. The number of radicals scavenged by each molecule of ubiquinol-10 is 1.1 under our experimental conditions. In contrast to alpha-tocopherol, ubiquinol-10 is not recycled by ascorbate. However, it is known that ubiquinol-10 can be recycled by electron transport carriers present in various biomembranes and possibly by some enzymes. We also show that ubiquinol-10 spares alpha-tocopherol when both antioxidants are present in the same liposomal membranes and that ubiquinol-10, like alpha-tocopherol, does not interact with reduce...