Nitric Oxide Metabolites and Dinitrosyl Iron Complexes in the Non-Enzymatic Glycation Reactions

Abstract

Non-enzymatic glycation (NEG) has to be studying in connection with other reactions. We have shown that methylglyoxal-caused NEG is accompanied with appearance of radical intermediates: methylglyoxal (MG) anion-radical and Schiff base cation-radical. Methylglyoxal anion-radical is responsible for formation of other radical products: superoxide, peroxynitrite and nitrogen dioxide. Nitric oxide (NO) donors S-nitrosothiols inhibite forming of fluorescent glycation products when bio-molecules (hemoproteins, albumin, carnosine) incubating with MG [1]. Other NO metabolites/donors also demonstrated antiglycating properties. The most effective were dinitrosyl iron complexes (DNICs). NO is stabilizing in DNICs. Thiol-containing DNICs (DNIC-Cys, DNIC-GS) are the most frequent. They are destroying by superoxide producing in glycation reactions and directly by MG. We have shown that MG destroys DNIC-Cys, but DNIC-GS are not disintegrating or are transforming to binuclear form. EPR spectroscopy displays appearance of new type DNICs [2]. MG also stimulates formation of carnosine-bound DNICs. MG-caused modification of amino acids and proteins leads to the new DNIC-fastening sites. Thus DNIC is the node of the reactions net uniting metabolism of ROS, RNS, reactive carbonyl compounds and thiols.