Abstract
The chemical processes taking place in humans intersects the myriad of metabolic pathways occurring in commensal microorganisms that colonize the body to generate a complex biochemical network that regulates multiple aspects of human life. The role of tryptophan (Trp) metabolism at the intersection between the host and microbes is increasingly being recognized, and multiple pathways of Trp utilization in either direction have been identified with the production of a wide range of bioactive products. It comes that a dysregulation of Trp metabolism in either the host or the microbes may unbalance the production of metabolites with potential pathological consequences. The ability to redirect the Trp flux to restore a homeostatic production of Trp metabolites may represent a valid therapeutic strategy for a variety of pathological conditions, but identifying metabolic checkpoints that could be exploited to manipulate the Trp metabolic network is still an unmet need. In this review, we put forward the hypothesis that pyridoxal 5′-phosphate (PLP)-dependent enzymes, which regulate multiple pathways of Trp metabolism in both the host and in microbes, might represent critical nodes and that modulating the levels of vitamin B6, from which PLP is derived, might represent a metabolic checkpoint to re-orienteer Trp flux for therapeutic purposes.
Highlights
Tryptophan (Trp) is an aromatic amino acid characterized by the presence of a side chain indole, a bicyclic structure consisting of a benzene ring fused to a pyrrole ring [1]
It was first found that the levels of vitamin B6 were associated with depression [19], and it was shown that vitamin B6 supplementation can protect from depression in certain clinical settings. These results indicate that the metabolism of Trp in mammals is dependent on vitamin B6 as two of the main Trp-metabolic pathways are regulated by pyridoxal -phosphate (PLP)-dependent enzymes, making vitamin B6 a plausible metabolic checkpoint in the regulation of Trp flux
The first three products are generated by the activity of PLP-dependent enzymes: indole is produced by tryptophanase, a PLP-enzyme that is activated by potassium ions; indole-3-pyruvic acid by PLP-dependent aromatic amino acid aminotransferases (AroAT); and tryptamine by a Trp decarboxylase, again dependent on PLP
Summary
Tryptophan (Trp) is an aromatic amino acid characterized by the presence of a side chain indole, a bicyclic structure consisting of a benzene ring fused to a pyrrole ring [1]. Trp metabolites can be generated by the host, and by other organisms that interact with the host. Trp is an essential amino acid in mammals and needs to be acquired from the diet, whereas, in general, bacteria, fungi, and higher plants express enzymes for Trp biosynthesis. The Trp metabolic pathways and the resulting bioactive molecules can either be shared or differ between mammals and other organisms [3]. All these characteristics create a network of inter-dependency and connectivity, centered around Trp and. IlantedrebstyinPgLlyP,-dcreiptiecnadl estnetpesniznytmhess.yInt tihsetshiesraenfodremliektaeblyoltihsamt voiftaTmrpin inB6m, farmommwalshiachndthme aicrtoivbeesfoarmre PrLegPuilsadteedrivbeyd,PmLPig-hdteipnetnerdseenct tehnezTyrmpems.etIat bioslitshmerteoforreegulilkateelyitsthflautx vaitlaomnginthBe6,dfirffoemrewnthmichettahbeoalicctipvaethfowrmayPs,LtPhuissdweorirvkeidng, masigahmt inetaebrsoelcict tchheecTkrpominett.abolism to regulate its fluxInaltohnisgrtehveiedwif,fewrenptrmoveitdabeoalnicopvaetrhvwieawyso, fthtuhse wmoertkaibnogliacsdaepmeentdabenolciec bchetewckepeoninvti.tamin B6 and Trp in mammals and microbes, discuss how the regulation of Trp flux may occur in function of vitamin B6 levels, and propose how the modulation of vitamin B6 levels may have potential therapeutic implications in pathological conditions
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
