Fig. 1.

Overview of the sources and fate of intra-neuronal catecholamines, with emphasis on enzymatic oxidation catalyzed by MAO. Dopamine (DA) is produced in the cytoplasm via tyrosine hydroxylase (TH) acting on tyrosine to form 3,4-dihydroxyphenylalanine (DOPA) and then L-aromatic-amino-acid decarboxylase (LAAAD) acting on DOPA to form dopamine. Most of cytoplasmic DA is taken up into vesicles by way of the vesicular monoamine transporter (VMAT). Dopamine-beta-hydroxylase (DBH) in the vesicles catalyzes the production of norepinephrine (NE) from DA. Cytoplasmic DA is subject to oxidative deamination catalyzed by monoamine oxidase-A (MAO-A) in the outer mitochondrial membrane to form 3,4-dihydroxyphenylacetaldehyde (DOPAL), and NE is deaminated to form 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL). DOPAL is converted to 3,4-dihydroxyphenylacetic acid (DOPAC) via aldehyde dehydrogenase (ALDH), and DOPEGAL is converted to 3,4-dihydroxyphenylglycol (DHPG) via aldehyde/aldose reductase (AR). Most of vesicular DA and NE released by exocytosis is taken back up into the cytoplasm via cell membrane transporters—the NET for NE (although DA is a better substrate than NE for uptake via the NET). DOPA can undergo spontaneous oxidation to DOPA-quinone (DOPA-Q), resulting in formation of 5-S-cysteinylDOPA (Cys-DOPA), and DA can undergo spontaneous oxidation to DA-quinone (DA-Q), resulting in formation of 5-S-cysteinylDA (Cys-DA)