Copper amine oxidases (CAOs) are a family of enzymes that convert endogenous amines to ammonia, hydrogen peroxide and aldehydes. To date, of t5he two types of CAOs, serum and membrane bound, the membranous CAOs have not been thoroughly studied. We intend to obtain the previously isolated clone for membranous CAO cDNA in order to express the enzyme in mammalian cells and characterize its kinetic properties, cofactor formation and catalytic mechanism. Given that CAOs are potential important in several diseases, we intend to synthesize hydrazine-based inhibitors by combinatorial methods. It is our hope that screening of these compounds will yield an inhibitor specific for membrane bound CAOs. We also intend to investigate the possible role of membranous CAO as a generator of H2O2 at the plasma membrane. It is possible that the slow, in situ generation of peroxide will act as a signaling agent, thereby influencing the genes responsible for cell death, cell proliferation and inflammation.
| Shen, Sam H; Wertz, Diana L; Klinman, Judith P (2012) Implication for functions of the ectopic adipocyte copper amine oxidase (AOC3) from purified enzyme and cell-based kinetic studies. PLoS One 7:e29270 |
