Fig. 1

DA metabolic pathways. DA is unstable and can undergo oxidation to produce reactive DOQ and ROS. The reaction can be reversed under sufficient ambient reductive force. The reactive DOQ can covalently conjugate with protein residues via MA reaction to form DOQ-protein adducts. DOQ can further be oxidized to generate ROS and AM, a cyclized DAQ. AM can also conjugate with protein residues to form AM-protein adducts via MA reaction or undergo internal rearrangement to form 5,6-dihydroxyindole, which can further polymerize to form melanin. Alternatively, DA can be catalyzed by COMT to form non-toxic 3-MT and finally HVA. DA can also be catalyzed by MAO to form reactive DOPAL and ROS. DOPAL can be catalyzed by ALDH to form non-toxic DOPAC and generate HVA under the catalysis of COMT. DOPAL can also be reduced by ALR/AR to form inactivate DOPAE. However, DOPAL is reactive and can conjugate with protein lysine residues to form DOPAL-protein adducts via SB reaction. DOPAL can be further oxidized to generate reactive ROS and DPQ, while DPQ can conjugate with protein residues via MA reaction to form DPQ-protein adducts. ALDH  aldehyde dehydrogenase, AM aminochrome, COMT catechol-o-methyltransferase, DA dopamine, DOPAL 3,4-dihydroxyphenylacetaldehyde, DOQ DA-o-quinone, DPQ DOPAL-quinone, HVA homovanillic acid, 3-MT 3-methoxytyramine