Tyrosine gives catecholamines, tryptophan gives serotonin, glutamate gives GABA
Mnemonic
Each transmitter comes from one amino acid:
- Tyrosine to dopamine to noradrenaline to adrenaline. The rate limiting step is tyrosine hydroxylase, and the pathway needs tetrahydrobiopterin
- Tryptophan to 5-hydroxytryptophan to serotonin to melatonin
- Glutamate to GABA, by glutamate decarboxylase, needing vitamin B6
- Choline plus acetyl-CoA to acetylcholine
- Histidine to histamine
“Tyrosine for the catecholamines, tryptophan for serotonin, glutamate for GABA.”
The pathway explains several treatments and diseases: levodopa bypasses tyrosine hydroxylase in Parkinson’s; phenylketonuria blocks phenylalanine to tyrosine, so tyrosine becomes essential and the pathway fails; and carcinoid tumours consume tryptophan for serotonin, which can cause pellagra because niacin is also made from tryptophan.
Vitamin B6 dependence of GABA synthesis is why isoniazid, which depletes B6, causes seizures in overdose, treated with pyridoxine.
Expansion
| Precursor | Products |
|---|---|
| Tyrosine | DOPA, dopamine, noradrenaline, adrenaline; also melanin and thyroid hormone |
| Tryptophan | Serotonin, then melatonin; also niacin |
| Glutamate | GABA, by glutamate decarboxylase (requires B6) |
| Histidine | Histamine |
| Choline | Acetylcholine |
| Arginine | Nitric oxide |
| Glycine | Inhibitory transmitter in the spinal cord |
Rate-limiting enzymes: tyrosine hydroxylase for the catecholamines and tryptophan hydroxylase for serotonin. Both require tetrahydrobiopterin, which is why defects in its synthesis cause a neurotransmitter deficiency that dietary phenylalanine restriction cannot correct.
Vitamin B6 is the cofactor for the decarboxylation steps throughout, which explains the seizures of pyridoxine-dependent epilepsy and of isoniazid overdose, both treated with pyridoxine.
Clinical connections: levodopa is given rather than dopamine because only the precursor crosses the blood-brain barrier; carcinoid syndrome diverts tryptophan to serotonin, causing pellagra; and methyldopa and carbidopa act on this pathway.