This new application outlines a broad and comprehensive program in the areas of bio-organic chemistry. Investigations described focus on mechanisms for flavin promoted oxidations of amines and related substrates. One major issue here is whether these reactions, occurring in chemical model or enzyme catalyzed processes, proceed by SET (radical) or polar (adduct formation) mechanisms. The planned studies, which combine model flavin chemical and enzymological efforts, have as their major goal the elucidation of the chemical mechanism for amine oxidation catalyzed by a class of physiologically important flavoenzymes known as the monoamine oxidases (MAO-A & -B). The mechanistic information gained from chemical and biochemical efforts will be used to develop novel strategies for the design of MAO-inactivators, substances which are known to play a significant role in the treatment of depression and Parkinson's disease. In addition, the techniques employed for elucidating the MAO-catalytic mechanism will be used to gain information about the potentially related catalytic pathways for flavin containing amino acid, alcohol and fatty acid ester dehydrogenases.
