A 15-year-old girl presents to a psychiatrist for an initial intake appointment. She reports decreased mood, decreased appetite, anhedonia, and difficulty concentrating for the past 3 months. She does not use any illicit substances, and her screening laboratory tests are unremarkable. A presumptive diagnosis is made.
Which of the following amino acids is necessary to synthesize the neurotransmitter whose synaptic concentration is increased by the first-line treatment for this patient’s condition?
- A) Histidine
- B) Isoleucine
- C) Threonine
- D) Tryptophan
- E) Tyrosine
This is a classic presentation of major depressive disorder. First-line treatment is a selective serotonin reuptake inhibitor (SSRI) which increases serotonin in the synapse by inhibiting the re-uptake transporter SERT. In serotonin synthesis, tryptophan is the starting molecule. Tryptophan is converted to 5-hydroxy-trypopthan by tryptophan hydroxylase. Then, 5-hydroxy-trypopthan is converted to serotonin (5-HT) by aromatic amino acid decarboxylase (DOPA decarboxylase).
Answer Choice A: Histidine, is incorrect. Histidine can be converted to histamine, essential to anaphylaxis, but not into serotonin.
Answer Choice B: Isoleucine, is incorrect. Isoleucine is a branched chain amino acid that can be converted into succinyl-CoA via multiple steps, then enter the TCA cycle. It is not a precursor to serotonin.
Answer Choice C: Threonine is incorrect. Threonine can be converted into succinyl-CoA to enter the TCA cycle, but it cannot be converted to serotonin.
Answer Choice E: Tyrosine is incorrect. The synthetic sequence of tyrosine as it relates to neurotransmission is tyrosine > L-DOPA > dopamine > norepinephrine > epinephrine. Importantly, tyrosine is also a precursor to melanin and thyroxine (T4). Tyrosine is not, however, a precursor to serotonin.
Key Learning Point
Tryptophan is the biosynthetic precursor to serotonin.
Dr. Ted O'Connell