Dopamine Biosynthesis

Dopamine biosynthesis

The primary fault in Parkinson's Disease is that, whatever the cause, there is insufficient dopamine. Dopamine is formed in the dopaminergic neurons by the following pathway :

L-tyrosine >>> L-dopa >>> Dopamine

The first step is biosynthesised by the enzyme Tyrosine 3-Monooxygenase [1.14.16.2] (which is more commonly called by its former name tyrosine hydroxylase). The following is the complete reaction :

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

So for L-dopa formation, L-tyrosine, THFA (tetrahydrofolic acid), and ferrous iron are essential. 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.

The second step in the biosynthesis of dopamine is biosynthesised by the enzyme Aromatic L-amino acid decarboxylase [4.1.1.28] (which is more commonly called by its former name dopa decarboxylase). The following is the complete reaction :

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

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 even far less.

Coenzymes involved in Dopamine biosynthesis

Besides two enzymes being required for the formation of dopamine from L-tyrosine (L-tyrosine >>> L-dopa >>> Dopamine), three coenzymes are also required. Enzymes are substances that will enable a specific chemical reaction to take place in the body. Coenzymes are substances that assist enzymes. Some enzymes (including those involved in dopamine biosynthesis) will not function without coenzymes.

The three coenzymes involved in the formation of dopamine are : THFA (for L-tyrosine to L-dopa), Pyridoxal phosphate (for L-dopa to dopamine), and NADH (for the formation of THFA and Pyridoxal phosphate). They are made from vitamins via the following means :

Folic acid >>> Dihydrofolic acid >>> Tetrahydrofolic acid

Pyridoxine >>> Pyridoxal >>> Pyridoxal 5-Phosphate (this requires zinc as a cofactor)

Nicotinamide >>> NMN >>> NAD >>> NADH (or NADP) >>> NADPH

PART 3 : CELL DAMAGE

The first step in the formation of dopamine (L-tyrosine > L-dopa > dopamine) is the formation of L-dopa from L-tyrosine.

L-dopa is normally formed in the dopaminergic neurons by the following pathway :

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

There are two problems with this reaction not working. Primarily, if somebody does not form L-dopa, they will also lack the dopamine required to prevent Parkinson's Disease from occurring. No L-dopa formation ends up in somebody developing Parkinson's Disease.

However, there is also a cellular symptom of a failure to form L-dopa from L-tyrosine. This is the cell damage that occurs in Parkinson's Disease.

The primary natural means via which cell damage can occur in Parkinson's Disease is due to the reaction from L-tyrosine to L-dopa not taking place. The following is what should happen :

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

However, if for example, the THFA in the above reaction is lacking, the following can happen instead :

L-tyrosine + Fe2+ + O2 >>> L-tyrosine + Fe3+ + O-2 (superoxide anion)

As can be seen there is no L-dopa formed in the faulty reaction, and the superoxide anion is formed instead. The superoxide anion is one of the most highly destructive elements in cells.  OXIDATIVE DAMAGE.   So you get a double problem : symptoms of Parkinson's Disease and cell damage.

The formation of L-dopa can also fail to take place if L-tyrosine is deficient.

So the simplest means of preventing cell damage from taking place is to ensure that you have those substances required for the formation of L-dopa, which are L-tyrosine, THFA (which is made from the vitamin folic acid using nicotinamide), and ferrous iron.

However, many people have instead tried to solve the problem of cell damage by other means, largely because they did not known the primary cause of the cell damage.

Vitamin C and Vitamin E have been used to try to help to prevent cell damage in Parkinson's Disease. This is because they are claimed to assist in two enzyme reactions in the brain that get rid of the superoxide anion once it has been formed :

Superoxide Dismutase [1.15.1.1] : 2O-2 + 2H+ >>> H2O2 + O2

Catalase [1.11.16] : H2O2 >>> H2O + 1/2 O2