Oxidative Modification of Rat Liver 5′-Nucleotidase: The Mechanismsfor Protection and Re-Activation.

The effect of oxidative stress catalysed by transition metals appears tohave a critical relevance for the structure and function not only of membranelipids but also of integral membrane proteins in a complex lipid-protein assembling,and membrane-dependent function. The integral membrane enzyme 5′-nucleotidaseis susceptible to Fe[sup [sup 2+] ] -ion catalysed oxidative modification,and the extent of enzyme inhibition is in inverse relationship (r = -0.820)with lipid peroxidation (MDA) level. This work is also a comparative studyabout possible effectiveness of different Fe-ion chelators (deferoxamine,Na-citrate, Na-salicylate, ammonium oxalate and EDTA), antioxidants (GSH,GSH/GSH-Px system, Cu, Zn-SOD and mannitol) and metal cations (Mg[sup 2+] and Mn[sup 2+] ) to protect or restore Fe[sup 2+] -ion induced 5′-nucleotidaseinhibition and to supress Fe[sup 2+] -ion enhanced lipid peroxidation.Among the examined chelators it was only deferoxamine and Na-citrate thatexerted a fully protective and reactivating ability; among the antioxidantsit was only GSH; among the metal cations it was only Mn[sup 2+] . Theability to protect or restore 5′-nucleotidase activity and to diminishchain-induced lipid peroxidation is explicable in terms of: metal-bindingability, capacity of taking iron away from a biological molecule, or abilityof transferring the damage to itself. After a short incubation period, theiron associated with enzyme or lipid hydroperoxides could be in a labile coordinativelinkage, still able to interact with possible ligands or metal cations. [ABSTRACT FROM AUTHOR]