Modeling the cascade of enzymatic reactions in liposomes including successive free radical peroxidation, reduction, and hydrolysis of phospholipid polyenoic acyls for studying the effect of these processes on the structural-dynamic parameters of the membranes.
Studies of the effect of primary products of free radical lipid peroxidation (LPO) on the structural-dynamic parameters of natural lipid-protein supramolecular complexes (biomembranes and blood serum lipoproteins) using standard inducers of radical processes in vitro (azo-initiators, transition metal ions, flavin oxidases, etc.) are impossible because of simultaneous production of numerous secondary LPO products that can induce structural changes. The data obtained suggest that phospholipid liposome microviscosity, as assessed by the extent of eximerization of the fluorescent probe pyrene, may significantly differ when oxidation is induced by animal C-15 lipoxygenase (yielding acylhydroperoxides only) and Fe(2+)-ascorbate system (resulting in simultaneous accumulation of primary and secondary LPO products). It is also shown that liver glutathione S-transferase can effectively reduce hydroperoxy-acyls in phospholipid liposomes and liver microsomes without their preliminary hydrolysis with phospholipase A(2). An enzymatic system is proposed for a cascade of enzymatic reactions simulating lipohydroperoxide metabolism in living cells, including successive free radical oxidation of phosphatidylcholine polyenoic acyls, reduction of their hydroperoxy-derivatives, and hydrolysis of fatty acid residues in the course of catalysis mediated by animal C-15 lipoxygenase, glutathione S-transferase, and phospholipase A(2), respectively.
Lankin
V Z
VZ
Russian Cardiology Research Complex, Ministry of Public Health of the Russian Federation, Moscow, 121552, Russia. lankin@vipmail.ru
Tikhaze
A K
AK
Osis
Yu G
YG
D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D021961:Cell Membrane Structures / Q000201:enzymology* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005609:Free Radicals / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006868:Hydrolysis; D007700:Kinetics; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism*; D008560:Membrane Fluidity; D008862:Microsomes, Liver; D010741:Phospholipases A / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
D005609:Free Radicals; D008054:Lipid Peroxides; D008081:Liposomes; D010743:Phospholipids; D001093:Arachidonate 15-Lipoxygenase; D005982:Glutathione Transferase; D010741:Phospholipases A