Molecule of the Month: Tryptophan

Good spread: The festive season is generally associated with may foods, of those turkey is very popular choice. One of the components of turkey, tryptophan is thought to cause sleep-inducing effects,.

TW: Article loosely discusses depression and low mood

The holiday season is associated with many things, bright lights, dark nights, lazy Boxing Day mornings, questionably bad Christmas movies and finally, turkey.

Undeniably, one of the best aspects of this season is the food – even coming from a person who doesn’t observe the holiday. Roast potatoes lathered in butter, aromatic rosemary sprinkled all over and juicy, rich mince pies are a few of the delicacies which can be seen during this time of the year

After such indulgence it is common for fatigue to set in. However, one particular festive food, turkey, has been prophesied to cause this food-induced coma. One of the components of turkey, tryptophan, has been of keen interest to the scientific community due to its claims that it can aid sleep. Some studies have even gone further to investigate how tryptophan could aid in the symptoms of depression and low mood.

Could turkey really the culprit of the post-dinner drowsiness?

More importantly, could tryptophan from the diet be used to beat the so-called January blues?

One molecule, four parts

Firstly, it is important to note that tryptophan is regarded as an amino acid, which is one of the essential building blocks, alongside nucleic acids and carbohydrates, that have allowed complex life to thrive on this planet1. Just like joining single Lego pieces together to create a much bigger structure, joining amino acids to one another are produces a larger structure called proteins which include complex enzymes to even the turkey sitting on your plate2.

Figure 1: General Amino Acid: Amino acids are the primary building blocks of proteins and are made up of four key groups. The variability between each of the amino acids comes from the differing ‘R’ group side chains

Generally, amino acids follow the same structure pattern (Figure 1)3 which are made of a basic amino group, an acidic carboxyl group, a hydrogen atom and an organic R side chain4. The variability found within amino acids arises from different R groups which can alter in size, shape and molecular make-up to one another5.

For example, the R group for the amino acid glycine is simply a hydrogen whereas, the one present in tryptophan has what is called an aromatic side chain(Figure 2)6 .

Figure 2: Side piece: Shows the side chains of glycine and tryptophan and how they chemically differ from one another. This chemical difference in bonds is related to the biological differences in function within the overall structure of the protein. (Image is adapted from source)

These R groups have differing chemical properties to one another and even a single amino acid change can change the structure and therefore, the functioning of a protein7.

Throughout nature, there are only 20 of these fundamental side chains, presenting that proteins of nearly every living organism is made from this small group of amino acids8.

As each R-chain and therefore, amino acid is distinct from one another they serve a purpose in the final form of a protein. Such R-groups can form complex, interlinking interactions and even bonds giving rise to beautiful three-dimensional structures and finally, proteins that are specific to a biological function2.

Back to essentials

Of these twenty amino acids, nine of these belong to an exclusive club named essential amino acids. Essential amino acids (Figure 3)9 are part of this group as they cannot be produced in the body, like the rest of them, but instead, need to be taken up by the diet4.

Figure 3: Just the essentials, please: Shows the structures and the R groups in red of the nine essential amino acids that human cannot produce, but instead need to obtained through the diet.

A deficiency in these essential amino acids can cause severe problems within humans as we need a variety of proteins to mainly absorb, transport and finally, oxidise other nutrients10. Not only does this present the need for a varied, healthy diet but shows the importance of these key amino acids.

As tryptophan belongs in this group and additionally, is required to synthesise signalling molecules such as serotonin and melatonin (Figure 4)11 which is known to mediate important processes such as sleep and mood it has been of great interest to scientists.

Figure 4: Complex pathway: Shows the various biochemical changes which tryptophan has to go through until it can produce serotonin and melatonin. The far left bar shows the biochemical structure of each intermediate, while the middle text shows the name of these compounds, the far right text shows the associated enzymes used to transform tryptophan and its intermediates.

Such links between tryptophan, sleep and mood are under investigation and might even be the origin story of the well-known “fact” shared around the Christmas table. However, can turkey really the culprit and moreover, could tryptophan be used to beat the post-Christmas slump?

Modern-day Myth

The well-known hypothesis that the tryptophan within turkey is the cause of post-dinner sleepiness is untrue. Although tryptophan is heavily involved in the process of producing melatonin, a molecule which regulates the natural sleep-wake cycle, its synthesis is tightly regulated and is not dependant on the amount of tryptophan in the blood12.

Melatonin is produced in the pineal gland, which is situated in the brain13. The rate at which melatonin is produced here is not dependant on the concentration of tryptophan but instead, the activity of the enzymes responsible for melatonin production14. In particular, the enzyme hydroxyindole-O-methyl-transferase (Figure 4) is thought to be the rate limiting enzyme of melatonin production, especially at night15.

Rate limiting enzymes can be thought as the slowest step in the creation of one compound to the next. Additionally, this rate limiting enzyme determines the rate at which melatonin is produced and not related to the concentration of the previous intermediates but instead, the activity of the enzyme itself 16.This presents the availability and rate of these enzymes, not the amount of tryptophan, determines the amount of melatonin produced.

Even if the melatonin did not rely on rate-limiting enzymatic function, turkey does not contain enough tryptophan in isolation to cause this effect. Other amino acids such as glutamic acid, lysine and arginine exist alongside tryptophan in turkey and is not abundant enough to illicit these sleep-inducing effects17. Additionally, foods such as chicken, milk and tuna have a similar, and sometimes even greater, tryptophan content, compared to turkey further presenting the tryptophan content of turkey is simply not large enough18.

Nevertheless, experimental studies have persisted to see if tryptophan-rich foods can indeed improve sleep quality. One study has found that tryptophan enriched cereal can improve sleep, melatonin and serotonin levels within 35 elderly volunteers11. However, similar studies have shown no difference in sleep. Within scientific circles, the effects of tryptophan, if any, on sleep is mixed and unclear. It is important to note that these studies also have differing methods, brining into question whether they can be directly compared to one another. Nevertheless, this presents a sizeable research gap which further investigation is required19 .

Serotonin & Tryptophan : Mystery to be solved

Serotonin is a molecule widely responsible for regulating mood and perception and there is evidence that impaired serotonin function and levels can be one of the causes of clinical depression20,21 .

Contrastingly to melatonin production, the rate at which serotonin is produced is directly dependent on the availability of tryptophan, especially within the brain22.Since the body cannot produce tryptophan alone, and requires consumption through diet, scientists have since opened studies to determine whether diet can alter tryptophan and serotonin levels to lift and alter mood in healthy and depressed populations.

Large scale studies focusing on changing tryptophan levels through diet alone are few and far between. Nevertheless, a study of 25 healthy young adults found that when participants were on the high-tryptophan diet their mood increased significantly compared to when they were on a low-tryptophan diet23. This evidence has not been found within larger-scale studies, presenting a difficulty to alter tryptophan levels, and therefore serotonin, through diet outside the scope of a research setting24.

Interestingly, a review of scientific literature into manipulating dietary tryptophan levels have found that healthy individuals are “insensitive” to these changes overall. Likewise, those who have a history of depression present inconsistent results presenting no clear correlation of altering tryptophan levels and the symptoms of depression24.

It is important to note however, that the links between diet and depression have been substantiated by the handful of control studies on the subject25. Although a causal relationship can be shown in this case, tryptophan-specific effects require further investigation and insight within all populations.

Essentially complicated

Although tryptophan may not be the cause of the food coma too many of us experience, they are an essential molecule which the body itself cannot make. Whether tryptophan, or associated diet changes can quell the slump in mood after the festivities are unfounded too. However, this is an emerging and not-well studied part of science that requires further exploration in the years to come. Nevertheless, amino acids, including tryptophan have a basic, common structure where their R-chains present opportunities for the body and nature to produce complicated and physiologically relevant protein compounds.

I hope all my readers have a cosy, serotonin-high festive season, whether you are observing Christmas, Hanukkah or the month of December.

Image references: Turkey: Karolina Grabowska, Sleeping: Ketut Subiyanto, Black&White: Umberto Shaw all from Pexels

Separator reference: https://www.flaticon.com/free-icon/turkey_616897?related_item_id=616731&term=turkey

References:

1.         PubChem. Tryptophan. https://pubchem.ncbi.nlm.nih.gov/compound/6305.

2.         Protein Structure | Learn Science at Scitable. https://www-nature-com.ezproxy.sussex.ac.uk/scitable/topicpage/protein-structure-14122136/.

3.         The Astrophysics & Astrochemistry Laboratory: Amino Acids and Their Production during the Photolysis of Astrophysically Relevant Ices. http://www.astrochem.org/sci/Amino_Acids.php.

4.         Lopez, M. J. & Mohiuddin, S. S. Biochemistry, Essential Amino Acids. in StatPearls (StatPearls Publishing, 2020).

5.         Lodish, H. et al. Hierarchical Structure of Proteins. Mol. Cell Biol. 4th Ed. (2000).

6.         lec5-aminoacids.pdf.

7.         Bromberg, Y. & Rost, B. Correlating protein function and stability through the analysis of single amino acid substitutions. BMC Bioinformatics 10, S8 (2009).

8.         Berg, J. M., Tymoczko, J. L. & Stryer, L. Proteins Are Built from a Repertoire of 20 Amino Acids. Biochem. 5th Ed. (2002).

9.         Joseph, M. The Nine Essential Amino Acids: Functions, Requirements, Sources. Nutrition Advance https://www.nutritionadvance.com/essential-amino-acids-functions/ (2019).

10.       Hou, Y. & Wu, G. Nutritionally Essential Amino Acids. Adv. Nutr. 9, 849–851 (2018).

11.       Bravo, R. et al. Assessment of the intake of tryptophan-enriched cereals in the elderly and its influence on the sleep-wake circadian rhythm. Antropol. Port. 29, 113–120 (2012).

12.       Tordjman, S. et al. Melatonin: Pharmacology, Functions and Therapeutic Benefits. Curr. Neuropharmacol. 15, 434–443 (2017).

13.       Aulinas, A. Physiology of the Pineal Gland and Melatonin. in Endotext (eds. Feingold, K. R. et al.) (MDText.com, Inc., 2000).

14.       Peuhkuri, K., Sihvola, N. & Korpela, R. Dietary factors and fluctuating levels of melatonin. Food Nutr. Res. 56, (2012).

15.       Liu, T. & Borjigin, J. N-Acetyltransferase is not the rate limiting enzyme of melatonin synthesis at night. J. Pineal Res. 39, 91–6 (2005).

16.       Zhao, M. & Qu, H. Human liver rate-limiting enzymes influence metabolic flux via branch points and inhibitors. BMC Genomics 10, S31 (2009).

17.       Fisher, C. & Scougall, R. K. A note on the amino acid composition of the Turkey. Br. Poult. Sci. 23, 233–237 (1982).

18.       Richard, D. M. et al. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Int. J. Tryptophan Res. IJTR 2, 45–60 (2009).

19.       Lindseth, G. & Murray, A. Dietary Macronutrients and Sleep. West. J. Nurs. Res. 38, 938–958 (2016).

20.       Berger, M., Gray, J. A. & Roth, B. L. The Expanded Biology of Serotonin. Annu. Rev. Med. 60, 355–366 (2009).

21.       Cowen, P. J. & Browning, M. What has serotonin to do with depression? World Psychiatry 14, 158–160 (2015).

22.       Fernstrom, J. D. Large neutral amino acids: dietary effects on brain neurochemistry and function. Amino Acids 45, 419–430 (2013).

23.       Lindseth, G., Helland, B. & Caspers, J. The Effects of Dietary Tryptophan on Affective Disorders. Arch. Psychiatr. Nurs. 29, 102–107 (2015).

24.       Soh, N. L. & Walter, G. Tryptophan and depression: can diet alone be the answer? Acta Neuropsychiatr. 23, 3–11 (2011).

25.       Ljungberg, T., Bondza, E. & Lethin, C. Evidence of the Importance of Dietary Habits Regarding Depressive Symptoms and Depression. Int. J. Environ. Res. Public. Health 17, (2020).

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