What are the primary enzymes involved in the metabolism of dopamine and norepinephrine after reuptake?

After reuptake into the presynaptic neuron, the primary enzymes involved in the metabolism of dopamine and norepinephrine are monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Dopamine and norepinephrine are removed from the synapse by reuptake transporters, specifically the dopamine transporter (DAT) and the norepinephrine transporter (NET), respectively. Once inside the neuron, these neurotransmitters can be either repackaged into vesicles for future release or metabolized by MAO and COMT. MAO is located both inside and outside the neuron and exists in two isoforms, MAO-A and MAO-B. MAO-A primarily metabolizes norepinephrine and serotonin, while MAO-B primarily metabolizes dopamine and phenylethylamine. Both isoforms can metabolize tyramine. MAO breaks down dopamine and norepinephrine into their respective metabolites, such as dihydroxyphenylacetic acid (DOPAC) from dopamine. COMT is located in the cytoplasm and also in glial cells. COMT metabolizes dopamine and norepinephrine by transferring a methyl group to the catecholamine structure. For example, COMT metabolizes dopamine to 3-methoxytyramine (3-MT) and norepinephrine to normetanephrine. The metabolites produced by MAO and COMT are further metabolized and eventually excreted. Therefore, MAO and COMT play a critical role in regulating the levels of dopamine and norepinephrine within the neuron after reuptake, and they are essential for maintaining neurotransmitter homeostasis.