Serotonin (5-HT)-synthesis, significance, clinical relevance

1. Serotonin (5-HT)

Synthesis:

Step 1: Conversion to 5-Hydroxytryptophan (5-HTP):

• Enzyme: Tryptophan hydroxylase

• Process: The enzyme tryptophan hydroxylase catalyzes the hydroxylation of tryptophan, an essential amino acid, converting it into 5-hydroxytryptophan (5-HTP).

• Cofactors Required: Tetrahydrobiopterin (BH4) and oxygen.

• Mechanism: BH4 acts as a cofactor, donating electrons, while oxygen adds a hydroxyl group (-OH) to the benzene ring of tryptophan, forming 5-HTP.

Step 2: Conversion to Serotonin:

• Enzyme: Aromatic L-amino acid decarboxylase (also known as DOPA decarboxylase).

• Process: 5-HTP is decarboxylated to form serotonin (5-hydroxytryptamine, 5-HT).

• Cofactor Required: Pyridoxal phosphate (vitamin B6).

• Mechanism: The enzyme removes a carboxyl group (-COOH) from 5-HTP, resulting in the formation of serotonin.

Significance:

1. Mood Regulation: Serotonin is crucial for maintaining mood balance and is often called the "feel-good" neurotransmitter. Low levels are associated with depression.

2. Appetite Control: It helps regulate hunger and satiety.

3. Sleep: Serotonin influences sleep cycles and is a precursor to melatonin.

4. Cognitive Functions: It aids in learning, memory, and cognitive processing.

5. Gastrointestinal Motility: Serotonin helps control bowel movements and functions.

6. Vasoconstriction: It causes the narrowing of blood vessels, which helps regulate blood flow.

Clinical Relevance:

• Psychiatric Disorders: Imbalances in serotonin levels are linked to conditions such as depression, anxiety, and obsessive-compulsive disorder (OCD).