In the past several weeks, there have been a number of posts about oxidative stress and the effects that it can have on neurotransmitter pathways, including the tryptophan pathway and catecholamine synthesis. Dopamine metabolism can also contribute to oxidative stress.
Dopamine is created from L-DOPA by the enzyme aromatic L-amino acid decarboxylase (AADC) (Figure 1). Dopamine is then broken down into DOPAL by monoamine oxidase B (MAOB) and DOPAC by aldehyde dehydrogenase (ALDH). The breakdown of dopamine to DOPAL creates a hydrogen peroxide molecule (H2O2). Hydrogen peroxide is a free radical and is also broken down into a hydroxide ion (HO–), which is also a free radical. Normally, free radical synthesis through the breakdown of dopamine is well controlled by the body. If the body becomes overwhelmed with free radicals, illness or disease symptoms can occur. An elevated DOPAC level can indicate increased dopamine breakdown, leading to increased levels of free radicals. This oxidative stress can affect neurotransmitter pathways. The neurotransmitter pathways, in turn, can also impact the total oxidative stress in a patient.
So, if you see elevated DOPAC levels in a patient, make sure you think about oxidative stress as a contributing factor.