Thanksgiving is just around the corner in the US, with the anticipated meal and the nap that follows. There have been several debates from where the sleepiness comes from after the Thanksgiving feast. Is it the copious amount of food, the warm-and-fuzzy feeling from being around families and friends, or the star-of-the-dinner-show turkey? There is a popular belief that the L-tryptophan found in turkey is to blame.

L-Tryptophan is an essential aromatic amino acid that can be found in several food sources including dairy, nuts, fish, and of course turkey.¹ Although turkey is thought to contain a high amount of L-tryptophan, the concentration of L-tryptophan in turkey is comparable to other meat such as pork, beef, and fish. So how did L-tryptophan get the blame for the sleepiness experienced after the Thanksgiving meal? Once L-tryptophan enters the body, it has been shown to participate in the biosynthesis of the neurotransmitter serotonin, and the hormone melatonin. The neurotransmitter serotonin regulates our mood, and virtually all our behavioral processes, whereas melatonin influences our sleep-wake cycles.² Both molecules can help us catch a nice snooze.

We can see the resemblance in the structures of these molecules in Figure 1.

 

 

Figure 1. Chemical structure of L-tryptophan, serotonin, and melatonin

In this blog post, we research whether we can see the resemblance or spot the differences between L-tryptophan and melatonin using NMR. We prepared samples of L-tryptophan (purchased from TCI) and melatonin (extracted from a supplemental tablet) in DMSO-d6, then collected 1D proton and 2D-COSY spectra of both samples on the Spinsolve 80 Carbon ULTRA benchtop NMR spectrometer.

Figure 2. 1D proton spectrum of 50 mM L-tryptophan (top) and 50 mM melatonin (bottom) acquired on Spinsolve 80 Carbon ULTRA. Each spectrum was acquired with 32 scans in 5.4 minutes.

Even though L-tryptophan and melatonin share the same indole aromatic ring motif, their 1D proton NMR spectra are quite different from each other (Figure 2). Melatonin has a methoxy substituent on the aromatic ring, which changes the coupling pattern in the aromatic region of the spectrum. Due to the methoxy substituent, the aromatic region of the melatonin spectrum has a simpler coupling pattern as compared to the 1D proton spectrum of tryptophan, with the integration of 4 protons. Melatonin’s two methyl groups can be observed as singlets at 1.80 and 3.76 ppm. The α and β protons can be seen clearly in the tryptophan 1D proton spectrum, while the signal from residual water from the tablet at 3.34 ppm masked the α-protons’ signals in the melatonin 1D proton spectrum.

The structures of L-tryptophan and melatonin can be further differentiated through their 2D-COSY spectra shown in Figure 3. More specifically, the correlation between the methyl group of the amide and the α-protons’ signals can be observed in the 2D-COSY spectrum of melatonin.

Figure 3. 2D-COSY spectrum of L-tryptophan (left) and melatonin (right) acquired on Spinsolve 80 Carbon ULTRA. Each spectrum was measured in 9 minutes.

 

The sleepiness you experience after the Thanksgiving meal might come from all that were mentioned at the beginning, the full belly after a bountiful meal, quality time with the families, and from serotonin and melatonin synthesized from L-tryptophan in the turkey. Perhaps after the Thanksgiving meal this year, you will think about these molecules as you drift off into dreamland. Happy Thanksgiving from us at Magritek!

References

1. Richard, D. M., Dawes, M. A., Mathias, C. W., Acheson, A., Hill-Kapturczak, N., & Dougherty, D. M. (2009). L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. International journal of tryptophan research: IJTR, 2, 45–60. https://doi.org/10.4137/ijtr.s2129
2. Paredes, S. D., Barriga, C., Reiter, R. J., & Rodríguez, A. B. (2009). Assessment of the Potential Role of Tryptophan as the Precursor of Serotonin and Melatonin for the Aged Sleep-wake Cycle and Immune Function: Streptopelia Risoria as a Model. International journal of tryptophan research: IJTR, 2, 23–36. https://doi.org/10.4137/ijtr.s1129