Lysine residues, oxidative deamination

After secretion from the cell, certain lysyl residues of tropoelastin are oxidatively deaminated to aldehydes by lysyl oxidase, the same enzyme involved in this process in collagen. However, the major cross-links formed in elastin are the desmosines, which result from the condensation of three of these lysine-derived aldehydes with an unmodified lysine to form a tetrafunctional cross-hnk unique to elastin. Once cross-linked in its mature, extracellular form, elastin is highly insoluble and extremely stable and has a very low turnover rate. Elastin exhibits a variety of random coil conformations that permit the protein to stretch and subsequently recoil during the performance of its physiologic functions. 

Tropoelastin molecules are crosslinked in the extracellular space through the action of the copper-dependent amine oxidase, lysyl oxidase. Specific members of the lysyl oxidase-like family of enzymes are implicated in this process (Liu etal, 2004 Noblesse etal, 2004), although their direct roles are yet to be demonstrated enzymatically. Lysyl oxidase catalyzes the oxidative deamination of e-amino groups on lysine residues (Kagan and Sullivan, 1982) within tropoelastin to form the o-aminoadipic-6-semialdehyde, allysine (Kagan and Cai, 1995). The oxidation of lysine residues by lysyl oxidase is the only known posttranslational modification of tropoelastin. Allysine is the reactive precursor to a variety of inter- and intramolecular crosslinks found in elastin. These crosslinks are formed by nonenzymatic, spontaneous condensation of allysine with another allysine or unmodified lysyl residues. Crosslinking is essential for the structural integrity and function of elastin. Various crosslink types include the bifunctional crosslinks allysine-aldol and lysinonorleucine, the trifunctional crosslink merodes-mosine, and the tetrafunctional crosslinks desmosine and isodesmosine (Umeda etal, 2001). 

Akagawa M, Sasaki T, Suyama K (2002), Oxidative deamination of lysine residue in plasma protein of diabetic rats. Novel mechanism via the Maillard reaction, Eur. J. Biochem. 269 5451-5458. 

K. Suyama, M. Akagawa, and T. Sasaki, Oxidative deamination of lysine residue in plasma protein from diabetic rat a-dicarbonyl-mediated mechanism, in G, 2002, 243-248. 

Newly formed collagen extracted with cold, aqueous NaCl solutions consists of three equal-sized chains (a-components) of two different composition types ( -l and -2). The two chains of similar composition are the a-1 chains. The a-2 chain differs from the a-1 in a number of amino acids, particularly hydroxyproline, proline, lysine, and histidine (26). As the collagen molecule matures, the a-chains crosslink intramo-lecularly in pairs this older protein can be readily extracted with acidic solutions such as dilute acetate and citrate buffer, but not with salt solutions. The crosslinked chains are called /3 components the crosslinks are probably covalent bonds (26) that arise by condensation of the side chains of strategic lysyl residues after enzymatic oxidative deamination. Older collageil also forms intermolecular bonds, but the nature of this crosslink has not yet been determined (27). 

In presence of transition metal cations and O2, a large number of phenolics exhibit also an amine oxidase-like activity (Akagawa Suyama, 2001). They convert lysine residues of proteins to a-amino-adipic semialdehyde residues. The oxidative deamination is initiated by the metal-catalyzed autooxidation of the phenolic compounds and by its reaction with the l,l-diphenyl-2-picryl hydrazyl (DPPH) radical, likely owing to the formation of quinine. But their biological significance and importance for plants remain to be understood. 

Incubation of protein with peroxidase/H202/cate-chol also results in cross-linking. The reactions in this case are the oxidative deamination of lysine residues, followed by aldol and aldimine condensations, i. e. reactions analogous to those catalyzed by lysyl oxidase in connective tissue ... 

The conversion of lysine to desmosine requires oxidative deamination of the g-amino group of lysine residues in preelastin chains. A reaction of this complexity is not likely to occur... 

Scheme I (Figure la) in presence of an oxidant, such as hydrogen peroxide, the stable end product 2-aminoadipic acid and glutamic acid will form. The adipic semialdehyde ( allysine ) can be assayed as reduced product, i.e. 6-hydroxynorleucine. However, in the lens the most likely pathway for allysine formation involves ascorbate (Stadtman ) or glycation of lysyl residues by ascorbate, glucose or methylglyoxal to form a metal complex that oxidatively deaminates lysine (figure lb)...

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