Histidine, with peroxidizing lipid

Histidine with peroxidizing lipid was altered both at the a-carbon and the imidazole side chain (23, 35). Histamine, imidazole acetic acid and imidazole lactic acid evidently... 

Caeruloplasmin (Cp) is an acute phase glycoprotein with a copper transport function. At least 90% of total plasma copper is bound to Cp with the remaining 10% associated with albumin, histidine and small peptides. Lipid peroxidation requires the presence of trace amounts of transition metals and the copper-containing active site of Cp endows it with antioxidant capacity... 

Thus, the mechanism of MT antioxidant activity might be connected with the possible antioxidant effect of zinc. Zinc is a nontransition metal and therefore, its participation in redox processes is not really expected. The simplest mechanism of zinc antioxidant activity is the competition with transition metal ions capable of initiating free radical-mediated processes. For example, it has recently been shown [342] that zinc inhibited copper- and iron-initiated liposomal peroxidation but had no effect on peroxidative processes initiated by free radicals and peroxynitrite. These findings contradict the earlier results obtained by Coassin et al. [343] who found no inhibitory effects of zinc on microsomal lipid peroxidation in contrast to the inhibitory effects of manganese and cobalt. Yeomans et al. [344] showed that the zinc-histidine complex is able to inhibit copper-induced LDL oxidation, but the antioxidant effect of this complex obviously depended on histidine and not zinc because zinc sulfate was ineffective. We proposed another mode of possible antioxidant effect of zinc [345], It has been found that Zn and Mg aspartates inhibited oxygen radical production by xanthine oxidase, NADPH oxidase, and human blood leukocytes. The antioxidant effect of these salts supposedly was a consequence of the acceleration of spontaneous superoxide dismutation due to increasing medium acidity. 

Protein cross-links may be also produced in reaction of 4-hydroxynonenal with lysine, histidine, serine, and cysteine residues, primarily via Michael addition (J5, R7, U8). These reactions occur spontaneously, but also may be catalyzed by certain glutatione 5-transferases. The glutathione transferase A4-4, which unlike other alpha-class glutathione transferases, shows high catalytic activity toward lipid peroxidation products such as 4-hydroxynon-2-enal, is the key enzyme for these reactions (B31). Products of protein coupling with aldehydes secondary to lipid peroxidation have a specific fluorescence, which can herald the protein oxidative modification process (CIO). 

Reactive aldehydes derived from lipid peroxidation, which are able to bind to several amino acid residues, are also capable of generating novel amino acid oxidation products. By means of specific polyclonal or monoclonal antibodies, the occurrence of malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE) bound to cellular protein has been shown. Lysine modification by lipid peroxidation products (linoleic hydroperoxide) can yield neo-antigenic determinants such as N-c-hexanoyl lysine. Both histidine and lysine are nucleophilic amino acids and therefore vulnerable to modification by lipid peroxidation-derived electrophiles, such as 2-alkenals, 4-hydroxy-2-alkenals, and ketoaldehydes, derived from lipid peroxidation. Histidine shows specific reactivity toward 2-alkenals and 4-hydroxy-2-alkenals, whereas lysine is an ubiquitous target of aldehydes, generating various types of adducts. Covalent binding of reactive aldehydes to histidine and lysine is associated with the appearance of carbonyl reactivity and antigenicity of proteins [125]. 

Studies on mice showed that certain organic zinc salts, such as aspartate, orotate, histidine, and acetate, alone or in conjunction with thiols, exhibited protective action against ethanol toxicity (Floersheim 1987). Corresponding Mg, Co, Zr, and Li salts showed similar action. Experimentation reduced lipid peroxides produced in the liver in chronic ethanol toxicity (Marcus et al. 1988). Vitamin E may have an antidotal action against alcohol toxicity. V-Acetylcysteine [616-91-1] is reported to combat ethanol-acetaminophen toxicity (Carter 1987). 

HNE-Modified Protein This arises by the covalent binding of HNE, an endogenously generated major lipid peroxidation product derived from breakdown of lipids containing u)-6 fatty acids (lin-oleic and arachidonic acid), to nucleophilic sites in the given protein. HNE reacts with the side chains of cysteine (Cys, C), histidine (His, H), and lysine (Lys, K) in an order of reactivity Cys His > Lys. 

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