Covid and Dopamine

Notes on an Interesting Article Linking Dopamine Dysregulation and Viruses

Introduction

A reader pointed me to a very interesting article “An alteration of the dopamine synthetic pathway is possibly involved in the pathophysiology of COVID‐19”. As someone with a Parkinson’s diagnosis, I have a keen interest in dopamine biosynthesis, and what can effect it, so I dug in to the article. I thought I would share my notes here, in case anyone else finds this interesting.

Starting with the punchline of the article:

“Moreover, in patients suffering from severe forms of COVID‐19, the hypothesis of a systemic failure of the dopamine [production] pathway should be taken into account and further explored.”

While interesting in itself, the papers has some other nuggets of pertinent information about dopamine more generally.

ACE2

First, I had to make myself some notes about “ACE2” [Angiotensin-converting enzyme 2] which we have heard so much about since the Covid era.

• ACE2 is an enzyme (a biological catalyst which can greatly accelerate the rate of a specific biochemical reaction, without being changed by that reaction itself) which can appear on the surface of cells, or free floating in the blood.

• ACE2 helps to keep the blood pressure in a healthy range. The reaction which ACE2 speeds up is the conversion Angiotensin-converting enzyme 2 into a vasodilating substance which lowers blood pressure.

• In its role as a cell receptor on the cell’s surface it is the entry/weak point for coronaviruses, including SARS-Cov-2, via the spike protein binding to the ACE2 and then creating a way for the virus to pass into the interior of the cell.

• The interaction with the spike protein (this, presumably, therefore applies to the spike generated by the vaccines too), also causes the ACE2 receptor itself to go inside the cell (“internalization”), causing damage to the cell.

DDC

• DDC (DOPA decarboxylase), also known as AADC (Aromatic L-amino acid decarboxylase), is another enzyme, responsible for speeding up the reaction rates of a number of important biochemical reactions.

• These reactions include: the conversion of l-dopa into dopamine (this is of most significant interest to folks with a Parkinson’s diagnosis, because l-dopa is still the basis of the mainstay drugs for this condition); l-tyrosine to tyramine; l-histadine to histamine; 5-HTP to serotonin;

• DDC can also both appear on cell surfaces as a receptor, or in free floating form.

The Hypothesis

According to the above linked article, “bioinformatic” data shows that ACE2 and DDC tend to co-express, or in other words the more ACE2 there is, the more DDC there tends to be.

“That ACE2 co-regulates with DDC indicates a possible functional link between the ACE2‐mediated synthesis of [blood pressure reducing substance] and the DDC‐mediated synthesis of dopamine and serotonin.”

The authors provide links to article which back this hypothesis up. They therefore postulate that since SARS-CoV-2, [and hence vaccine generated spike], causes ACE2 to be downregulated (internalized) and disappear from view inside the cells, the noted co-expression with DDC may also cause the DDC to be downregulated too. Thus, importantly, spike generated ACE2 damage may also result alterations in dopamine (and also serotonin, tyramine, and histamine) biosynthesis.

They describe one possible example of dopamine synthesis in the gut.

“ACE2 and DDC are both highly expressed in intestinal epithelial cells. Since intestinal epithelial cells were shown to convert L‐DOPA into dopamine and to provide an important source of blood‐circulating dopamine, one may hypothesize that a defective expression of ACE2 and DDC in intestinal cells may translate into altered levels and/or regulation of dopamine in the blood of patients with COVID‐19.”

Other Interesting Things About Dopamine

One of the interesting facts about dopamine which the authors mention, in passing, is that dopamine also has a role in the lungs. I knew that dopamine was important in other areas of the body outside the brain, including the gut (where 50% of our dopamine is made), the retina, the kidneys, etc., but I did not know it was important in the lungs too.

“… experiments performed in mice demonstrate that dopamine may shape lung immunity via dopamine receptors expressed by alveolar epithelial cells, lung macrophages, and lung terminal nerves.”

Another interesting nugget is that dopamine has already been shown to have anti-viral effects on some other viruses.

“The potential protective role of dopamine in the context of viral infections has been poorly investigated until now. In this regard, it is worth noting that in a recent work, DDC was found to negatively regulate the replication of the Flaviviridae viruses dengue and hepatitis C”.