Copper-dependent amine oxidases

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). 

Copper-dependent amine oxidases contain a type II copper (83-85). The yellow-pink color of amine oxidase implies the existence of another organic cofactor whose identification has not yet been unambiguously... 

Although there are flavin-dependent as well as copper-dependent amine oxidases, this section will only deal with the copper enzymes. Amine oxidase (EC 1.4.3.6) catalyzes the oxidative reaction of amines to aldehydes and ammonia. The two-step process generates two electrons which are utilized to reduce oxygen to hydrogen peroxide (H202) [28,113] ... 

From the above studies it can be concluded that plant tissues contain a specific enzyme for the degradation of naturally occurring cytokinins having a A isopentenyl side chain. Mechanistically it would appear to be a copper-dependent amine oxidase. From the widespread occurrence of adenine and related compounds as metabolites of externally applied A isopentenyl cytokinins [8], it may be concluded that cytokinin oxidase is present in a large number of plant species. 

When a crude preparation of amine oxidase was added to the culture medium, the ratio of lysine to desmosine was decreased in aortas from both copper-deficient and copper-supplemented chicks. These experiments were a strong indication that a copper-dependent amine oxidase is involved in the elastin cross-linking process. 

Abstract The copper-dependent amine oxidases (CuAOs) and flavin-containing polyamine oxidases (PAOs) are involved in polyamine (PA) catabolic processes. Studies on plant CuAOs are still incomplete, whereas research on plant PAOs has advanced significantly in the past decade. The maize PAO, the best smdied plant PAO, and the barley PAOs were shown to catalyze PAs in a terminal catabolic pathway. Therefore, plant PAOs were assumed to have terminal catabolic activity, which differs from the back-conversion activity of mammalian PAOs. However, plant PAOs that have back-conversion activity are now reported. Here, studies on PAOs from the two model species Arabidopsis thaliana and Oryza sativa are compiled, and research on CuAOs is updated. Our current understanding of the roles of PAOs and CuAOs in plant development and defense responses is described. 

Keywords Arabidopsis thaliana, back-conversion pathway Copper-dependent amine oxidase Oryza sativa, plant, polyamine oxidase Terminal catabolism pathway... 

From the sequence of reactions found it follows that copper-quinoprotein amine oxidases catalyze an aminotransferase reaction. A different reaction sequence occurs with flavoprotein amine oxidases (EC 1.4.3.4), where formation of NH3 is not dependent on the presence of 02. However, since reductive trapping of amines in the first half-reaction [86] showed attachment of substrate but not of tritium, the mechanism is also different from the aminotransferase reaction that... 

In the course of developing an enzymatic cascade-reaction for the production of amines from alcohols, naftifine, a potent antifungal agent, was synthesized [148]. Cinnamyl alcohol was oxidized in a one-pot reaction with a copper-dependent galactose oxidase to the corresponding aldehyde, which was subsequently subjected to reductive amination by co-TA. AlaDH was employed to recycle the amine donor l-alanine (Figure 13.36). Ciimamylamine was produced with 92% conversion and further transformed into naftifine in 51% overall yield over four steps. 

In contrast to the flavin-dependent monoamine oxidases, SSAO/VAP-1 has evolved to hydroxylate a tyrosine residue in the active site which is further oxidized to the quinone state by oxygen in the presence of copper ion releasing hydrogen peroxide [28-30]. The primary amine in the substrate (R-NH2, Scheme 1) forms a Schiff-base with the quinone carbonyl group, which through a series of steps ultimately releases the aldehyde product. 

I.3. Reduced Forms of the Enzyme. The hydrolysis of the product Schiff-base to release product and generate the aminoquinol form of the cofactor may involve water which has been retained in the active site. Dooley and co-workers have provided direct evidence for copper reduction during the interaction of amine oxidases with substrate under anaerobic conditions (Dooley et al., 1991). By varying the temperature at which EPR spectra were recorded, it was shown for amine oxidases from several sources that there is a temperature dependent equilibrium between Cu V aminoquinol TPQ and Cu / TPQ semiquinone. The Cu / TPQ semi-quinone form was found to be stabilised in the presence of cyanide. The... 

Figure 5 Illustration of possible partial reaction cycles of some copper- and flavin-dependent oxidase enzymes, (a) Copper amine oxidase 30, 31 (b) galactose oxidase (32) (c) catechol oxidase (10) (d) multicopper oxidases (10) (e) flavin oxidases (30) (f) cytochrome c oxidase (38).

Copper-dependent enzymes include tyrosinase (which is involved in melanin pigment formation) and the various oxidases (i.e., cytochrome oxidase, superoxide dismutase, amine oxidase, and uricase). Copper plays a major role in the incorporation of iron into the heme of hemoglobin. Copper deficiency is characterized by hypochromic, microcytic anemia resulting from defective hemoglobin synthesis. 

Structure. Diamine oxidases are homo-dimeric enzymes. The subunits weigh between 60 and 105 kD depending upon the organism of origin [114]. Human diamine oxidase from kidneys is composed of 752 amino acid residues, and the corresponding enzyme from rat colon has 747 residues [29]. Diamine oxidases share the TOPA-chinon cofactor with amine oxidases. The ligands of the type 2 copper center in diamine oxidase are possibly the conserved residues Cys 391, Cys 417, and His 510 [29]. 

Copper amine oxidases Ubiquinones, plasto-quinones, vitamin K Vitamin K-dependent carboxylation Vitamin E... 

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