The synthesis of neurotransmitters such as serotonin and dopamine depends on a series of well-orchestrated biochemical processes that involve specific amino acid precursors (the building blocks of protein), coenzymes (molecules that help enzymes function), and micronutrient cofactors (vitamins and minerals required for chemical reactions).

 

Serotonin is synthesized from the essential amino acid tryptophan (a precursor found in protein-rich foods), which is first converted to 5-hydroxytryptophan (5-HTP) via the enzyme tryptophan hydroxylase—a process requiring iron (a mineral that supports oxygen transport and enzymatic activity), magnesium (a mineral that regulates over 300 enzymes), vitamin C (an antioxidant and cofactor), and BH4 (tetrahydrobiopterin, a coenzyme involved in neurotransmitter synthesis). 5-HTP is then converted into serotonin with the help of vitamin B6 (in its active form, pyridoxal-5-phosphate).

 

Once serotonin is produced, it can be further converted into melatonin (a hormone that regulates sleep) in the pineal gland through two enzyme-dependent steps involving serotonin N-acetyltransferase (requires acetyl-CoA, a molecule central to energy metabolism, and magnesium) and hydroxyindole O-methyltransferase (HIOMT), which uses SAMe (S-adenosylmethionine, a key methyl donor) for methylation.

 

Similarly, dopamine is synthesized from the amino acid tyrosine (another protein building block), which is converted into L-DOPA via tyrosine hydroxylase (dependent on iron and BH4), and then into dopamine by the enzyme DOPA decarboxylase, which also requires vitamin B6.

 

These neurotransmitter pathways also rely heavily on optimal methylation. This process requires folate (as L-methylfolate, the active form of vitamin B9), vitamin B12, choline (a nutrient involved in brain development and neurotransmission), and zinc (a mineral essential for enzyme function and neurotransmitter release). If any of these nutrients are deficient—or if inflammation diverts tryptophan down the kynurenine pathway (which leads to neurotoxic metabolites rather than serotonin)—neurotransmitter production can become impaired.

 

Contributing situations or reasons tryptophan is diverted to the kynurenine pathway include chronic stress, systemic inflammation, immune activation, and elevated cortisol levels. These conditions stimulate the enzyme indoleamine 2,3-dioxygenase (IDO), which redirects tryptophan—generally used for serotonin and melatonin synthesis—into the kynurenine pathway. This biochemical shift reduces serotonin availability, leading to depression, fatigue, irritability, anxiety, cognitive disturbances, and sleep dysregulation.​

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