Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans

Abstract

L-Tryptophan is the unique protein amino acid (AA) bearing an indole ring: its biotransformation in living organisms contributes either to keeping this chemical group in cells and tissues or to breaking it, by generating in both cases a variety of bioactive molecules. Investigations on the biology of Trp highlight the pleiotropic effects of its small derivatives on homeostasis processes. In addition to protein turn-over, in humans the pathways of Trp indole derivatives cover the synthesis of the neurotransmitter/hormone serotonin (5-HT), the pineal gland melatonin (MLT), and the trace amine tryptamine. The breakdown of the Trp indole ring defines instead the “kynurenine shunt” which produces cell-response adapters as L-kynurenine, kynurenic and quinolinic acids, or the coenzyme nicotinamide adenine dinucleotide (NAD+). This review aims therefore at tracing a “map” of the main molecular effectors in human tryptophan (Trp) research, starting from the chemistry of this AA, dealing then with its biosphere distribution and nutritional value for humans, also focusing on some proteins responsible for its tissue-dependent uptake and biotransformation. We will thus underscore the role of Trp biochemistry in the pathogenesis of human complex diseases/syndromes primarily involving the gut, neuroimmunoendocrine/stress responses, and the CNS, supporting the use of -Omics approaches in this field.

Kynurenine pathway metabolism and the microbiota-gut-brain axis

“…As the precursor molecule to serotonin (5-HT), kynurenine and downstream metabolites of the kynurenine pathway (Badawy, 2015a;Palego et al, 2016), changes in the supply and availability of the essential amino acid tryptophan has many implications for ENS and CNS functioning and thus brain-gut axis signalling. Around 95% of the body's 5-HT is located within the GI tract, primarily synthesised by enterochromaffin cells, and 5% in the CNS (Camilleri, 2002;Gershon and Tack, 2007;Mayer et al, 2001).…”

Biomedical Significance of Tryptamine: A Review

“…[25]. The scavenging properties of circadian regulators, N-acetyl-5-HT (NAS) and melatonin (MLT) is due to indoleamines in 5-HT moiety and through "kynurenine shunt" a number of molecules produce in vertebrates and humans, are involved in inflammation, excitatory neurotransmission, immune response and many other functions [26].…”

Production and Function of Serotonin in Cardiac Cells

“…Peroral treatment of animals or humans with tryptophan (an essential amino acid) increases body concentrations of tryptophan. Uptake of tryptophan in the gut is brought about by the protein transporter enzymes SLC6A19 and SLC16A10 [25]. Protein-rich food is known to compete with these transporters and will lead to lower levels of tryptophan in the body [25].…”

“…Uptake of tryptophan in the gut is brought about by the protein transporter enzymes SLC6A19 and SLC16A10 [25]. Protein-rich food is known to compete with these transporters and will lead to lower levels of tryptophan in the body [25]. Effects of 5-HT in the heart were usually thought to be due to 5-HT released from intact platelets.…”