Copper catalyzed oxidative deamination

Several analogous systems which have been previously studied, may be reexamined in view of the mechanism suggested for the copper-catalyzed oxidative deamination. It was reported by Nyilasi that copper and cobalt ions catalyze the... 

Copper-containing amine oxidases (non-blue copper proteins) catalyze the oxidative deamination of primary amines to the corresponding aldehydes with the release of ammonia and concomitant reduction of oxygen to hydrogen peroxide. They typically use a quinone redox cofactor [topaquinone (TPQ)], which is bound covalently in the active site, and are thought to form a Cu(I)-TPQ semi-quinone radical intermediate during the redox reaction [13]. 

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). 

The copper amine oxidases (CAOs) catalyze the oxidative deamination of primary amines to aldehydes and the production of H202 for use in cell signaling. The... 

The collagen molecules formed by removal of the propeptides spontaneously assemble into fibrils. At this stage, the fibrils are still immature and lack tensile strength, which is acquired by cross-linking. The initial step in cross-link formation is the oxidative deamination of a-amino groups in certain lysyl and hydroxyly-syl residues catalyzed by lysyl oxidase. The enzyme is a copper-dependent (probably cupric) protein, and the reaction requires molecular oxygen and pyridoxal phosphate for full activity. Only native collagen fibrils function as substrates. 

Copper amine oxidases (EC 1.4.3.6) [CAOs, amine O2 oxidoreductase (deaminating)] catalyze the oxidative deamination of biogenic amines to corresponding aldehydes and ammonia, accompanied by a two-electron reduction of molecular oxygen to hydrogen peroxide [7] ... 

Oxidative Deamination Reactions. The enzymes amine oxidases (AOs) catalyze the oxidative deamination of a wide range of biogenic amines. There are two classes of AOs copper AOs and flavin-containing AOs. Copper-containing AOs catalyze the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone (TPQ) (2,4,5-trihydroxyphenylalanine) as cofactor (Figure 1.50). 

These homodimeric enzymes, that are present in both prokaryotic and eukaryotic organisms, contain one Cu ion and one redox-active cofactor topaquinone (TPQ) per monomer [5, 6]. They catalyze the oxidative deamination of primary amines [7-9]. The Cu(ll) ion is coordinated by three histidine residues and three water molecules (Fig. 11.1). The TPQ cofactor is not far from the Cu ion. The process can be divided into an initial reductive reaction followed by an oxidative step, based on the redox state of TPQ the Cu ion is thought to be involved in the formation of the TPQ semiquinone through reduction of Cu(II) to Cu(I). An alternative hypothesis has been recently proposed where the copper ion stays as Cu(II) and the one-electron reduction of O2 is carried out by a modified amino-resorcinol TPQ cofactor. The Cu(II) would provide electrostatic stabilization to the superoxide anion intermediate [10-12]. The reduction of molecular oxygen would result in weakly Cu-bormd hydroperoxide which is subsequently displaced by a water molecule, gets protonated and it is eliminated as hydrogen peroxide. 

Further step in the pathway is reaction catalyzed by the diamine oxidase enzyme, Ai-methylputrescine oxidase (MPO EC 1.4.3.6). This enzyme leads to oxidatively deamination of Ai-methylputrescine 13 to 4-(methylamino)butanal 14, which after spontaneous cyclization forms the reactive precursor of the tropane nucleus -7/-methyl-A -pyrrolinium cation 20 [2, 7, 36]. This enzyme requires copper as a cofactor and belongs to a class of amine oxidases. cDNA was isolated from tobacco [37]. This enzyme has been isolated by root cultures of H. niger L.,... 

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