Following release, NE receptor activation and reuptake by NE transporter (NET), NE is degraded by three main enzymatic pathways. (1) In the first pathway, MAO (monoamine oxidase) and ALDH (aldehyde dehydrogenase) convert NE into 3,4-dihydroxymandelic acid (DHMA); this compound is then processed by catechol-O-methyltransferase (COMT) into vanillylmandelic acid (VMA). (2) In the second pathway, MAO and ALR (aldehyde reductase) convert NE into 3,4-dihyroxyphenylglycol (DHPG), which is further degraded by COMT into 3-methoxy-4-hydroxyphenylglycol (MHPG). (3) In the third pathway, COMT metabolizes NE into normetanephrine (NM), which is then converted into either MHPG (via MAO/ALR) or VMA (via MAO/ALDH).