L-Tryptophan decarboxylase
L-Tryptophan decarboxylase is an enzyme distinguished by the substrate L-tryptophan.
This enzyme catalyzes the reaction of L-tryptophan to tryptamine and carbon dioxide. The enzymatic reaction namely takes place in the species Psilocybe cubensis, where a decarboxylase, kinase, and methyltransferase work together to synthesize psilocybin.
Classification
The enzyme commission number for L-tryptophan decarboxylase is EC 4.1.1.105. Other common names include psilocybin biosynthesis decarboxylase and psiD. The first digit in the enzyme number is representative of the class of enzymes known as lyases, which catalyze elimination reactions. The second and third digits are representative of the subclass of lyases known as decarboxylases that cleave carbon-carbon bonds. The last digit is representative of the enzyme's specific substrate, L-tryptophan.This enzyme is a part of the PLP-independent phosphatidylserine decarboxylase family and most compared to hypothetical proteins of other basidiomycetes fungi. These include Fibulorhizoctonia sp with 60% identical amino acids and Moniliophthora roreri with 52% identical amino acids. A similar enzyme that is not related to L-tryptophan decarboxylase is called aromatic-L-amino-acid decarboxylase with an enzyme number of EC 4.1.1.28.
Reaction pathway
The first step in the reaction is the substrate binding of L-tryptophan, which reacts with a coenzyme hydrogen. The decarboxylase enzyme is able to transform L-tryptophan to tryptamine in the second step by cleaving off two oxygens and a carbon to form tryptamine and carbon dioxide as the products. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, which makes the molecule polar, while tryptamines have an indole ring structure, a fused double ring consisting of a pyrrole ring, and a benzene ring, which is joined to an amino group by two carbon side chains.This is the chemical reaction that takes place:
Organisms in which L-tryptophan decarboxylase is found
L-Tryptophan decarboxylase has been characterized in bacteria, plants, and fungi. Fungi that produce psilocybin and psilocin express incredible diversity, as they are a part of at least eight genera with hundreds of species belonging to them. The specific reaction pathway for L-tryptophan decarboxylase has been described in twelve species, including Psilocybe cubensis, commonly known as magic mushrooms. All fungi in the genus Psilocybe have a well-defined, umbrella-like cap with gills underneath and a stipe. Other main characteristics of Psilocybe species include purple-brown reproductive spores, the presence of an annulus, and blue bruising with contact. All Psilocybe species are described to feed on microscopic detritus and are found on a variety of surfaces, such as herbivore dung, grasses, roots, wood, and soil. Humans have a documented history of ingesting this psilocybin producing fungi. There are 57 species that are found in Mexico, and out of these there have been reports of 35 species and nine varieties being used by ethnic groups.Function
In Psilocybe cubensis, L-tryptophan decarboxylase has been described with two other enzymes to biosynthesize psilocybin in a one pot reaction. These other two enzymes in this process are psiK, an enzyme that catalyzes the phosphotransfer step, and psiM, an enzyme that catalyzes the iterative N-methyl transfer step. The biosynthesis of psilocybin takes place as follows:L-Tryptophan is decarboxylated to 4-hydroxytryptamine by psiD → psiK phosphorylates 4-hydroxytryptamine to create norbaeocystin → psiM then processively N,N-dimethylates the compound to yield psilocybin.
Serotonin 2A receptors stimulation by the active metabolite, psilocin, disrupts serotonergic neurotransmission and produces the characteristic psychedelic effects of this species of fungus. The product formed by L-tryptophan decarboxylase, tryptamine, is relevant to humans because the mammalian brain contains very low concentrations of tryptamine; and serotonin is a tryptamine natural derivative involved in regulating central nervous system processes like sleep, cognition, memory, temperature regulation and behavior. In contrast, the naturally occurring derivatives of tryptamine are found in magic mushrooms.''