process

Tryptophan to 5-HTP conversion

The biosynthesis of 5-HTP starts with the essential amino acid tryptophan, which is metabolized to 5-HTP by TPH in an initial, rate-limiting step in the biosynthesis of serotonin after the decarboxylation catalyzed by aromatic amino acid decarboxylase (AADC). TPH is a monooxygenase that belongs to the family of aromatic amino acid hydroxylases; it incorporates one atom of oxygen from molecular oxygen into the substrate and reduces the other atom to water. The two electrons required for the reduction of the second atom to water are supplied by tetrahydrobiopterin (BH4), which acts as a substrate rather than a tightly bound cofactor, binding and dissociating each turnover [56]. The irreversible activation of O2 is the initial step in this mechanism and utilizes two electrons from BH4 to form a high-valent Fe(IV)O (ferryl) hydroxylating intermediate and 4a-hydroxypterin (4a-HOPH3). The Fe(IV)O intermediate subsequently reacts with the side chain of the aromatic amino acid through electrophilic aromatic substitution [57,58]. The binding of both the amino acid and BH4 results in a change in the coordination of the iron from six-coordinate to five-coordinate, presumably opening a coordination site for oxygen. The hydroxylating intermediate Fe(IV)O in TPH has been confirmed by rapid freeze-quench 57Fe Mössbauer spectroscopy [57]. During L-tryptophan hydroxylation, BH4 is oxidized to pterin-4α-carbinolamine (BH3OH) and regenerated through the function of pterin-4α-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR) [59,60].

Ref:
Maffei ME. 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology. Int J Mol Sci. 2020 Dec 26;22(1):181. doi: 10.3390/ijms22010181. PMID: 33375373; PMCID: PMC7796270.

20 confidence points
0 comments
Added on Oct 22, 2023 by Barbara Van De Keer

Join Ninatoka!!

NinatoKa's goal is to support you as a therapist in unravelling the illness pathway from symptoms to cause, and to help you detect potential interventions.

Go to Explore to start your discovery!

Go to Learn to scroll through newly added data.

Go to Contribute to contribute to the Ninatoka database.

You can rate content up or down and add comments if you agree or disagree.