Biochemistry behind Parkinson’s disease

We all know that Parkinson’s disease is a neurodegenerative disease, so let’s take a look at the main components that are involved.

Firstly we have acetylcholine and its cholinergic receptors, which is responsible for stimulation muscle contraction. Next, we have Dopamine and its dopamine receptors, which have an opposite effect – to inhibit muscle contraction.

Now, most of you would be thinking that Parkinson’s disease is caused by the excess of acetylcholine therefore the effect of dopamine is less than that of acetylcholine. But that is not true; in fact, it’s the deficiency of dopamine that causes this neurodegenerative disease.

Dopamine is produced in the dopaminergic neurons, and they are cells that do not reproduce. However study has shown that it is not the physical lack of dopaminergic neurons that causes Parkinson’s, but the reduction of dopamine activity in the brain.

Knowing what a crucial component Dopamine is in this neurodegenerative disease, let’s take a look at how it is formed (in 2 steps):

L-tyrosine → L-dopa → dopamine

Step 1: Biosynthesis of L-dopa by the enzyme tyrosine hydroxylase. The following is the complete reaction:

L-tyrosine + THFA + O2 + Fe2+ → L-dopa + DHFA + H2O + Fe2+

*THFA is a coenzyme derived from folic acid (vitamin)

The activity of this enzyme is often as low as 25% in Parkinson's disease and in severe cases can be as low as 10%. This indicates that one or more of the elements required for the formation of L-dopa are in insufficient quantities.

Step 2: Biosynthesis of dopamine is by the enzyme aromatic L-amino acid decarboxylase. The following is the complete reaction:

L-dopa + pyridoxal phosphate → dopamine + pyridoxal phosphate + CO2

* pyridoxal phosphate is a coenzyme derived from pyridoxine (vitamin)

So for dopamine biosynthesis from L-dopa, pyridoxal phosphate is essential. The activity of the enzyme rises and falls according to how much pyridoxal phosphate there is. The level of this enzyme in Parkinson's disease can also be around 25% or less.

*NADH which is also a coenzyme for the formation of both THFA and pyridoxal phosphate. All these coenzymes are essential too.

G protein is also an important component involved to relieve or aggravate Parkinson's disease. They must be stimulated by the following pathway.

L-tyrosine → L-dopa → dopamine → dopamine receptors (D2, D3, D4) > G proteins

What matters to Parkinson's disease are the alpha subunits of G protein, because it is actually these that ultimately relieve (or aggravate) Parkinson's disease. There are five types:

• G proteins that aggravate Parkinson's disease : Gs 1 alpha
• G proteins that relieve Parkinson's disease : Gi 1 alpha, Gi 2 alpha, Gi 3 alpha
• G proteins that have little effect on Parkinson's disease : Go alpha

The sole purpose of dopamine (or dopamine agonists) stimulating dopamine receptors is to cause the alpha subunits (the active part of G proteins) to break away from the rest of the G protein. Without this occurring almost everybody would have Parkinson's disease.

Once the alpha part of G proteins is released, via cyclic AMP, it takes the final action in the series of event that leads to the ridding of Parkinson's disease, which is to inhibit the cells it has effect on.