L-Theanine: A Major Constituent of Tea (Camellia sinensis)

Tea plant (Camellia sinensis) from Köhler's Medicinal Plants, 1897

Tea is an ancient drink. It was grown 2100 years ago to cater for the drinking habits of the Western Han Dynasty, in western Tibet, China (Lu et al. (2016)).

Aside from the stimulant, caffeine, a major constituent of tea (Camellia sinensis) is the non-protein amino acid L-theanine. Theanine represents about 1% of the dry weight of green tea leaves although there are substantial differences between cultivars of Camellia sinensis in terms of theanine levels (Liu et al. (2017), Cheng et al. (2019)).

Theanine is an amide; a compound derived from L-glutamate and ethylamine. The precise origin of the ethylamine moiety of theanine has been the subject of debate, but this point has recently been clarified. Bai et al. (2019) recently discovered that ethylamine is synthesized by an alanine decarboxylase with similarity to previously identified serine decarboxylases. Earlier studies by Cheng et al. (2017) had indicated that ethylamine availability is a major reason for the difference in L-theanine accumulation between C. sinensis and other plants. Most plants contain the enzyme/gene catalyzing the conversion of ethylamine and L-glutamic acid to L-theanine. After supplementation with [²H₅]ethylamine, all the plants produce [²H₅]L-theanine (Cheng et al. (2017)). Thus, the presence/absence of alanine decarboxylase seems to determine ethylamine availability, and hence theanine accumulation. Deng et al. (2009) had previously shown, by radiotracer studies, that alanine is the precursor of the ethylamine moiety of theanine, and that the metabolism of alanine to ethylamine is higher in roots than other organs. Consistent with this, the newly identified alanine decarboxylase is expressed predominantly in young roots (Bai et al. (2019)).

Proposed pathway of synthesis of L-theanine

The enzyme that forms theanine from the substrates L-glutamate and ethylamine appears to be none other than glutamine synthetase (Mu et al. (2015)) which is ubiquitous in the plant kingdom. However, Camellia sinensis appears to have evolved a specialized form of glutamine synthetase (now designated L-theanine synthetase) (Wei et al. (2018)) with a higher affinity for ethylamine than ammonia.

Ashira (2015) summarizes the biosynthesis and metabolism of theanine in Camellia sinensis succinctly as follows:

Biosynthesis of theanine from glutamic acid and ethylamine by theanine synthetase is present in all organs of tea seedlings, but roots are the major site of theanine biosynthesis in adult tea trees. Theanine is transported from roots to young leaves via the xylem sap. Theanine is hydrolysed to glutamic acid and ethylamine in leaves. Ethylamine produced from theanine is predominantly used for catechin biosynthesis. From: Ashira (2015).

Differences in the rate of catabolism of theanine may be the primary cause of cultivar differences in theanine content (Cheng et al. (2019)).

Green tea has been used in traditional Chinese medicine for centuries (Saeed et al. (2017)). Theanine represents over 50% of total free amino acids in tea and has a significant contribution to the quality of green tea (Bai et al. (2019)). Theanine is one of the metabolites in tea that account for its rich taste and health benefits (Wei et al. (2018)). Much interest has been devoted to assessing the effects of L-theanine on mood, mental alertness and arousal (Nobre et al. (2008), Dietz and Dekker (2017)).

Williams et al. (2019) urge human trials to further investigate the anti-inflammatory and antioxidant properties of L-theanine.

"Several studies have reported that the consumption of this amino acid has many therapeutic effects, including improvements in brain and gastrointestinal function, cancer drug therapeutic efficacies, antihypertensive effects, and improved immune function" (Williams et al. (2019)).

While consumption of green tea is generally considered safe, there have been alarming reports of hepatotoxicity associated with green tea consumption (Mazzanti et al. (2015)). It is unclear at present whether these adverse effects are due to deliberate or unintentional contamination of the green tea with other plant tissues containing toxic alkaloids such as pyrrolizidine alkaloids (Schulz et al. (2015)).

References:

Ashihara, H. Occurrence, biosynthesis and metabolism of theanine (gamma-glutamyl-L-ethylamide) in plants: a comprehensive review. Nat. Prod. Commun. 10: 803-810 (2015)

Bai, P., Wei, K., Wang, L., Zhang, F., Ruan, L., Li, H., Wu, L., Cheng, H. Identification of a novel gene encoding the specialized alanine decarboxylase in tea (Camellia sinensis) plants. Molecules 24: pii: E540 (2019)

Cheng, S., Fu, X., Wang, X., Liao, Y., Zeng, L., Dong, F., Yang, Z. Studies on the biochemical formation pathway of the amino acid L-theanine in tea (Camellia sinensis) and other plants. J. Agric. Food Chem. 65: 7210-7216 (2017)

Cheng, S., Fu, X., Liao, Y., Xu, X., Zeng, L., Tang, J., Li, J., Lai, J., Yang, Z. Differential accumulation of specialized metabolite L-theanine in green and albino-induced yellow tea (Camellia sinensis) leaves. Food Chem. 276:93-100 (2019)

Deng, W.W., Ogita, S., Ashihara, H. Ethylamine content and theanine biosynthesis in different organs of Camellia sinensis seedlings. Z. Naturforsch. C. 64: 387-390 (2009)

Dietz, C., Dekker, M. Effect of green tea phytochemicals on mood and cognition. Curr. Pharm. Des. 23: 2876-2905 (2017)

Liu, Z.W., Wu, Z.J., Li, H., Wang, Y.X., Zhuang, J. L-Theanine content and related gene expression: novel insights into theanine biosynthesis and hydrolysis among different tea plant (Camellia sinensis L.) tissues and cultivars. Front Plant Sci. 8: 498 (2017)

Lu, H., Zhang, J., Yang, Y., Yang, X., Xu, B, Yang, W., et al. Earliest tea as evidence for one branch of the Silk Road across the Tibetan Plateau. Sci. Rep. 6: 18955 (2016)

Mazzanti, G., Di Sotto, A., Vitalone, A. Hepatotoxicity of green tea: an update. Arch. Toxicol. 89: 1175-1191 (2015)

Mu, W., Zhang, T., Jiang, B. An overview of biological production of L-theanine. Biotechnol. Adv. 33: 335-342 (2015)

Nobre, A.C., Rao, A., Owen, G.N. L-Theanine, a natural constituent in tea, and its effect on mental state. Asia Pac. J. Clin. Nutr. 17 Suppl 1: 167-168 (2008)

Saeed, M., Naveed, M., Arif, M., Kakar, M.U., Manzoor, R., et al. Green tea (Camellia sinensis) and L-theanine: medicinal values and beneficial applications in humans - a comprehensive review. Biomed. Pharmacother. 95: 1260-1275 (2017)

Schulz, M., Meins, J., Diemert, S., Zagermann-Muncke, P., Goebel, R., Schrenk, D., Schubert-Zsilavecz, M., Abdel-Tawab, M. Detection of pyrrolizidine alkaloids in German licensed herbal medicinal teas. Phytomedicine 22: 648-656 (2015)

Wei, C., Yang, H., Wang, S., Zhao, J., Liu, C., Gao, L., et al. Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality. Proc. Natl. Acad. Sci. U.S.A. 115: E4151-E4158 (2018)

Williams, J., Sergi, D., McKune, A.J., Georgousopoulou, E.N., Mellor, D.D., Naumovski, N. The beneficial health effects of green tea amino acid L-theanine in animal models: promises and prospects for human trials. Phytother. Res. Jan 10. [Epub ahead of print] (2019)