Dopamine Precursors and Cofactor Supplements to Boost Production

Dopamine precursors like L-phenylalanine and L-tyrosine are required for the synthesis of all catecholamine neurotransmitters.

Phenylalanine and tyrosine are both amino acids which constitute the first two preliminary steps in the dopamine biosynthesis pathways. They are then used to make L-DOPA, which is converted into dopamine by the enzyme DOPA decarboxylase with the help of the cofactor Vitamin B6.

Dopamine serves as a precursor for the synthesis of other catecholamines including adrenaline (epinephrine) and noradrenaline (norepinephrine). These catecholamines are excitatory chemicals and influence cognitive functions like learning, movement, emotional state, sleep, sex drive, creativity and more.

In simplest form, the primary catecholamine synthesis pathway looks like this:

Phenylalanine –> Tyrosine –> L-Dopa –> Dopamine –> Norepinephrine –> Epinephrine

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Dopamine Precursor: Phenylalanine

To manufacture dopamine and other catecholamine hormones, the brain requires certain raw materials.

Neurotransmitters like dopamine are chemical substances which are made from micronutrients found in the diet – like amino acids, enzymes, vitamins and minerals.

The first dopamine precursor necessary is the essential alpha amino acid: L-phenylalanine (C9H11NO2).

Being “essential” for an amino acid means that the body cannot synthesize it. It must be gained from the diet, or via dietary supplementation.

Phenylalanine then gets converted to tyrosine via the monooxygenase enzyme: phenylalanine hydroxylase.

This reaction causes the attachment of a hydroxyl group to the end of phenylalanine’s 6-carbon aromatic ring. When there is dysfunction in the phenylalanine biosynthesis pathway, tyrosine synthesis is subsequently affected.

If phenylalanine hydroxylase is unavailable for any reason, then tyrosine cannot be metabolized. This deficiency is called PKU (phenylketonuria).

PKU is an autosomal recessive disorder that occurs when the liver lacks phenylalanine hydroxylase. If left untreated, brain and nervous system damage may result.

PKU is a lifelong condition in most cases. If it is detected early, then it can be treated effectively. By adhering to a PKU diet and routinely taking certain supplements, PKU symptoms can be minimized or entirely negated.

Dopamine Precursor: Tyrosine

The second required dopamine precursor is the proteinogenic alpha amino acid: tyrosine (C9H11NO3).

Also known as 4-hydroxyphenylalanine, tyrosine is considered conditionally essential. That means that it becomes essential only in cases where it cannot be biosynthesized; as in cases of PKU. Then it must be gained from foods or supplements.

Tyrosine gets converted to L-DOPA in humans, as well as certain other animals and some plants. This is catalyzed by the enzyme tyrosine hydroxylase (tyrosine 3-monooxygenase).

The conversion also requires cofactors of molecular oxygen, tetrahydrobiopterin and iron (Fe2+). This conversion process is the rate-limiting step in the synthesis of dopamine and of all catecholamines.

Tyrosine hydroxylase is a dopamine precursor enzyme which is found in peripheral sympathetic nerves, the CNS and the adrenal medulla.

Along with phenylalanine hydroxylase and tryptophan hydroxylase, tyrosine hydroxylase comprises the AAAH (aromatic amino acid hydroxylases) family.

Dopamine Precursor: DOPA

There is common confusion concerning the differences between the terms “DOPA”, “L-DOPA” and “levodopa”.

DOPA is an amino acid also called dihydroxyphenylalanine. It is comprised of a molecule of phenylalanine and two hydroxyl groups. DOPA occurs naturally in many animals and plants.

In mammals, DOPA is biosynthesized inside the liver from tyrosine during the production of epinephrine and melanin. Its L isomer then travels across the blood brain barrier to be converted into dopamine inside the brain.

L-DOPA and levodopa are terms used to denote the levorotatory form of DOPA. This can be manufactured in laboratories and is commonly used to treat Parkinson’s disease and other conditions associated with low dopamine symptoms.

As a nootropic, L-DOPA is used to enhance memory, focus and learning capacities. It is also used to prevent and treat depression, anxiety and the effects of chronic stress.

Common trade names for pharmaceutical-grade L-DOPA include Prolopa, Atamet, Madopar, Stalevo and Sinemet.

Certain herbaceous plants contain concentrated amounts of natural L-DOPA. The best known of these in Mucuna pruriens seeds (velvet beans) which are comprised of roughly 5% L-DOPA.

Other good sources are Vicia faba (broad beans, fava beans) – and botanic genera including Canavalia, Cassia, Dalbergia, Phanera and Piliostigma.

DOPA to Dopamine Conversion

The precursor L-DOPA (C9H11NO4) is converted into dopamine (C8H11NO2) via the actions of the enzyme dopa decarboxylase. This lyase enzyme is also called aromatic L-amino acid decarboxylase – or more simply: AAAD.

This same enzyme is responsible for converting 5-HTP into serotonin, L-histidine into histamine, phenylalanine into phenylethylamine, L-tyrosine into tyramine and tryptophan into tryptamine.

In all of these processes, the conversion basically involves the removal of carboxyl groups. Carboxyl groups are comprised on two O2 atoms, one C atom and one H atom.

DOPA decarboxylase also uses the active form of vitamin B6 (pyridoxal phosphate) as a cofactor for this conversion process.

Conclusions

Phenylalanine, tyrosine, oxygen, iron, vitamin B6 and certain other micronutrients and enzymes are required precursors for dopamine biosynthesis.

Dysfunction in any part of the dopamine synthesis pathway can result in serious disruptions of all catecholamine neurotransmitters, which can negatively affect mood, attention span, energy levels and mental drive.

In most healthy individuals, availability of dopamine precursors can be kept stable via a proper diet, regular exercise and effective stress management. Dopamine-boosting supplements can also be used to naturally remedy signs of deficiency.

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