1992 Syntex Award Lecture Model biomembranes: quantitative studies of peroxidation, antioxidant action, partitioning, and oxidative stress

Abstract

Tlris lecrure is dedicated ro Keith Irzgolcl L. R. C . BARCLAY. Can J. Chem. 71, 1 (1993). This review outlines a decade of research that employs quantitative kinetic methods of autooxidation to phospholipids aggregated into membranes. The classical rate law for autoxidation: was found to apply to heterogeneous systems of bilayers and micelles, where k, and 2k, are the rate constants for chain propagation and termination, respectively, and R,, the rate of chain initiation, is controlled b thermal initiators. The oridizobility of a typical lipid chain, linoleate 18:2, at 30°C was similar (0.02-0.04 M -" S -'~) in different media (solution, micelles, bilayers) and for different procedures using water-soluble or lipid-soluble initiators and inhibitors. A reduction in the absolute rate constant for termination, 2k,, by a hundredfold in bilayers of dilinoleoylphosphatidyl choline (DLPC) compared to that in rerr-butyl alcohol solution, and a drop in the k, by a factor of five are interpreted in terms of diffusion of polarized peroxyl radicals from the hydrophobic bilayer phase to the aqueous surface, where peroxyls are strongly solvated by water. Such phenomena may also account for significant changes as observed by "P NMR spectra in bilayer lamellar structure accompanying extensive peroxidation. Analysis of the hydroperoxides formed by peroxidation of mixed bilayers of DLPC + DPPC (16:O) initiated by a water-soluble initiator, azobis(2-amidinopropane.Hc1) (ABAP), showed a linear trend between the ratio of cis,trarzs to trnrls,frarzs geometrical isomeric hydroperoxides and [DPLC] consistent with a peroxidation mechanism proposed in homogeneous solution.The antioxidant activities, k,,,, of three classes of antioxidants: (a) polyalkyl-6-hydroxychromans (e.g., vitamin E), (0) polyalkyl-4-methoxyphenols, and (c) trialkylphenols, were measured in DLPC membranes. The results show an overall leveling and depression of k,,,', values in DLPC membranes in the series ( a ) (by several orders of magnitude), (b), and (c) compared to known values in solution in chlorobenzene. In aqueous bilayers it is proposed that kin,, values are attenuated by hydrogen bonding by water at both the p a r a ether oxygen and phenolic groups-. Restricted diffusion (e.g., of a-tocopherol) may also reduce antioxidant activities in membranes. A synergistic effect between ascorbic acid and atocopherol was discovered under conditions of inhibited peroxidation of linoleate in SDS micelles. The natural peptide glutathione, GSH, however, acts as a co-nrztio.ri~111rt with vitamin E by trapping peroxyls in the aqueous phase.Solid cholesterol was found to partition directly into PC lipsomes by shaking, above or below the phase transition temperature, and membrane-bound cholesterol, unlike the solid, undergoes facile peroxidation. A water-soluble form of c--tocopherol complexed with bovine serum albumin (a-toc:BSA) is an effective antioxidant for autoxidations of linoleate in SDS micelles. In contrast, a-toc:BSA required a long equilibration time (e.g., 12 h) wi...

Carbon Radicals of Low Reactivity against Oxygen: Radically Different Antioxidants

“…[22] The antioxidative activity of the radical-dimer systems was quantified by two standard assays: the inhibition of the autoxidation of cumene (isopropylbenzene) and styrene (vinylbenzene). [23] The reactions were initiated by thermal decomposition of 2,2'-azobisisobutyronitrile in chlorobenzene at 30 8C in the presence of air and the rapidly formed 2-cyanoisopropylperoxyl radical (R'OOC) starts the reaction chain. According to Scheme 3, in the presence of dimers A 2 and radicals AC, a competition between chain propagation (oxygen consumption) and chain termination is established.…”

Biomimetic Chemistry: Radical Reactions in Vesicle Suspensions

“…This can be the reason for quite contrasting results reported in the literature. For example, linoleic acid, taken as typical example of unsaturated fatty acid, has a similar oxidizability in different media as determined by different procedures (0.02 -0.04 M -1/2 s -1/2 ) (Barclay, 1993). The systematic determination of oxidizability in the extended homologous series of PUFA and comparison with the literature values have been done, indicating an increase value by increasing the number of bisallylic carbons.…”

Untitled

“…Unlike reactive free radicals, aldehydes can produce lipid peroxidation products, which are rather long lived and can therefore diffuse from the site of their origin, reaching and attacking intracellular and extra cellular targets 24 . They disrupt various important structural and protective functions associated with bio-membranes in various in-vivo pathologic events and are implicated as a result of this oxidation 25 .…”