Investigating Amine Oxidase Domain Containing Genes - amx-1 and amx-2 - in Caenorhabditis elegans

Monoamine (MA) neurotransmitters affect multiple behaviors in animals. MA homeostasis is achieved partly by monoamine-oxidase (MAO) enzymes - a drug target for many human neuropsychiatric disorders. In C. elegans the MA pathway is similar to that in humans and the worm shows MA dependent behaviors, affected by MAO inhibitor (MAOI) treatments. We cloned, expressed and purified the C. elegans genes - amx-1 and amx-2 in heterologous systems. Absorption spectra indicated that AMX1 and AMX2 bind the redox cofactor flavin adenine dinucleotide (FAD). Biochemical assays with wild-type (N2) or mutant worm lysates showed significant differences in MAO and histone demethylase (HDM) activities between them. Purified AMX1 and AMX2 had very low in vitro HDM activity independently, but both significantly increased the HDM activity of worm lysates. AMX1 had negligible in vitro MAO activity, whereas AMX2 had high in vitro MAO activity, with substrate and inhibitor specificities.