Dopamine: synthesis, significance, clinical relevance

3. Dopamine

Synthesis:

Step 1: Conversion to L-DOPA:

• Enzyme: Tyrosine hydroxylase.

• Process: Tyrosine is hydroxylated to form L-dihydroxyphenylalanine (L-DOPA).

• Cofactors Required: Tetrahydrobiopterin (BH4) and oxygen.

• Mechanism: BH4 acts as a cofactor, and oxygen adds a hydroxyl group to the benzene ring of tyrosine, forming L-DOPA.

Step 2: Conversion to Dopamine:

• Enzyme: Aromatic L-amino acid decarboxylase.

• Process: L-DOPA is decarboxylated to form dopamine.

• Cofactor Required: Pyridoxal phosphate (vitamin B6).

• Mechanism: The enzyme removes a carboxyl group from L-DOPA, resulting in the formation of dopamine.

Significance:

1. Movement Regulation: Dopamine is crucial for the coordination of voluntary movements.

2. Motivation and Reward: It plays a key role in the brain's reward system, influencing motivation, pleasure, and reinforcement learning.

3. Basal Ganglia Function: Dopamine is essential for the proper functioning of the basal ganglia, a brain region involved in movement control.

Clinical Relevance:

1. Parkinson's Disease: Characterized by low levels of dopamine in the brain, leading to movement disorders.

2. Schizophrenia: Linked to dysregulation of dopamine pathways.

3. Addiction: Dopamine pathways are involved in the mechanisms of addiction and reinforcement of addictive behaviors.