Dopamine, DA is known as a catecholamine or a catechol group attached to an amine group, figure 3. The characteristic of a catechol is two hydroxy groups, -OH, attached to a benzene ring. The catechol molecular structure is important to understand. It is the transformation of the catechol, down a chain of oxidative changes, which results in a quinone. The quinone is further discussed in the dopamine metabolism section.
Fig. 3, Dopamine
Dopamine is initially produced from L-Tyrosine or L-Phenylalanine, see figure 4. This conversion to dopamine can go by 2 different pathways. The predominate pathway is conversion to L-Dihydroxyphenyl alanine, L-DOPA, by Tetrahydrobiopterin. L-DOPA is then conversion to dopamine by aromatic amino acid decarboxylase, AADC. The less predominant pathway is the conversion of both tyrosine and phenylalanine to Tyramine. Tyramine is then hydroxylated by CYP2D proteins forming Dopamine.
Fig. 4 Meiser et al. Cell Communication and Signaling 2013, 11:34 http://www.biosignaling.com/content/11/1/34
Dopamine’s Metabolic Pathways, Inflammation and DNA Damage
The metabolism of a catechol has a risk of developing the highly reactive oxidative species, quinone, -Q. Dopamine is a catecholamine and has the same quinone metabolism risk, figure 5.
The characteristic of a quinone, -Q, is a highly reactive oxidative species, ROS, which readily binds to the purine molecule of DNA. The affinity of this quinone to the purine has stronger a binding than the purine to the DNA and the dopamine-quinolone-purine complex breaks off from the DNA forming a dopamine-DNA adduct and damaging the DNA. In other words, in the production of DA by the neuronal cell, the DA can form a DA-Q, which could result in cellular DNA damage and subsequently, apoptosis or transcription dysfunction resulting in decrease DA production.
Fig. 5 Intramolecular 1,4-Michael addition of dopamine quinone at neutral pH to form neuromelanin and competitive intermolecular 1,4-Michael addition at pH 5–6, with formation of the depurinating adducts DA-6-N3Ade and DA-6-N7Gua. Formation of Dopamine Quinone-DNA Adducts and their Potential Role in the Etiology of Parkinson’s Disease. Zahid M. et al.