Tryptophan metabolism

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Touchet
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Tryptophan metabolism

Post by Touchet »

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Last edited by Touchet on Sun 30 Dec 2007, 18:52, edited 1 time in total.
"Jos ihmismieli on ihmeellisin asia mitä maa päällään kantaa, pyrkimys tutkia narkoottisten ja stimuloivien aineiden psykofysiologisen vaikutuksen syvyyksiä saa tämän ihmeen vaikuttamaan vieläkin suuremmalta."
— Professori Louis Lewin, 1924
Kalastaja

Re: Tryptophan metabolism

Post by Kalastaja »

Oikealla suurin piirtein keskellä kohdan [EC] 2.1.1.49 jälkeen (joka edustaa indolietyyliamiini-N-metyylitransferaasia 'INMT', tunnetaan myös amiini metyylitransferaasina) olevasta N-metyylitryptamiinista tulee toisen 2.1.1.49 entsyymireaktion jälkeen N,N-Dimetyylitryptamiinia. (Jacob & Presti, 2005)

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  • Kuva Jacob & Presti 2006. Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine. Med.Hyp. 64(5). 2005.

Entrez Gene. [EC 2.1.1.49] - INMT indolethylamine N-methyltransferase [ Homo sapiens ]:
http://www.ncbi.nlm.nih.gov/sites/entre ... arch=11185

http://en.wikipedia.org/wiki/Amine_N-methyltransferase


EC 4.1.1.28 - Aromatic L-amino acid decarboxylase (AAAD) - Aromatic amino acid decarboxylase
(AADC):
http://en.wikipedia.org/wiki/Aromatic-L ... arboxylase

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Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine
Michael S. Jacob and David E. Presti
Medical Hypotheses. Volume 64, Issue 5, 2005, Pages 930-937

The presence of the potent hallucinogenic psychoactive chemical N,N-dimethyltryptamine (DMT) in the human body has puzzled scientists for decades. Endogenous DMT was investigated in the 1960s and 1970s and it was proposed that DMT was involved in psychosis and schizophrenia. This hypothesis developed from comparisons of the blood and urine of schizophrenic and control subjects. However, much of this research proved inconclusive and conventional thinking has since held that trace levels of DMT, and other endogenous psychoactive tryptamines, are insignificant metabolic byproducts. The recent discovery of a G-protein-coupled, human trace amine receptor has triggered a reappraisal of the role of compounds present in limited concentrations in biological systems. Interestingly enough, DMT and other psychoactive tryptamine hallucinogens elicit a robust response at the trace amine receptor. While it is currently accepted that serotonin 5-HT(2A) receptors play a pivotal role in the activity of hallucinogenic/psychedelic compounds, we propose that the effects induced by exogenous DMT administration, especially at low doses, are due in part to activity at the trace amine receptor. Furthermore, we suggest that endogenous DMT interacts with the TA receptor to produce a calm and relaxed mental state, which may suppress, rather than promote, symptoms of psychosis. This hypothesis may help explain the inconsistency in the early analysis of endogenous DMT in humans. Finally, we propose that amphetamine action at the TA receptor may contribute to the calming effects of amphetamine and related drugs, especially at low doses.

http://dmt-nexus.com/doc/endogenous%20a ... %20DMT.pdf


Tämä kannattaa myös katsoa:

Rabbit Lung Indolethylamine N-Methyltransferase. cDNA and gene cloning and characterization.
Michael A. Thompson and Richard M. Weinshilboum
J Biol Chem, Vol. 273, Issue 51, 34502-34510, December 18, 1998

Indolethylamine N-methyltransferase (INMT) catalyzes the N-methylation of tryptamine and structurally related compounds. This reaction has been studied because of its possible role in the in vivo synthesis of psychoactive compounds or neurotoxins and has been characterized biochemically in preparations of rabbit lung. Therefore, we set out to purify rabbit lung INMT, to clone and express its cDNA, and to clone and structurally characterize its gene as steps toward understanding the function and regulation of this enzyme. Rabbit lung INMT was purified and partial amino acid sequence was obtained. A polymerase chain reaction-based approach was then used to clone a rabbit lung INMT cDNA with a 792-base pair open reading frame that encoded a 263-amino acid protein with a predicted molecular mass of 29 kDa. When the cDNA was expressed in COS-1 cells, the encoded protein catalyzed the methylation of tryptamine and structurally related compounds, and was inhibited by two products of the reaction, S-adenosyl-L-homocysteine (AdoHcy) and N,N-dimethyltryptamine, as well as antimigraine drugs that are structurally related to N,N-dimethyltryptamine. Northern blot analysis demonstrated the presence of 2.0-kilobase mRNA species in rabbit lung, liver and, at lower levels, in brain. The cDNA was then used to clone the rabbit INMT gene. That gene had three exons and was structurally similar to the genes for nicotinamide N-methyltransferase and phenylethanolamine N-methyltransferase in several species. Cloning and expression of a rabbit lung INMT cDNA and cloning of the rabbit INMT gene represent important steps toward determination of the function and regulation of this mammalian methyltransferase enzyme.

http://www.jbc.org/cgi/content/full/273/51/34502

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Enzymatic Formation of Psychotomimetic Metabolites from Normally Occurring Compounds
Julius Axelrod
Science 4. August 1961: Vol. 134. no. 3475, p. 343

An enzyme has been found that N-methylates serotonin and tryptamine to psychotomimetic metabolites, bufotenine and N,N-dimethyltryptamine. This enzyme is highly localized in the rabbit lung and also N-methylates phenylethylamine derivatives such as tyramine, phenylethylamine , mescaline, and dopamine.

Online pdf (Jos ei ole tunnuksia jonkin yliopiston kautta, saa artikkelin auki niinkin suurella taikuudella kuin, että menee artikkelin abstraktiin yllä olevan "Rabbit Lung" -artikkelin linkistä (toinen viite) ja avaa sitten sitä kautta "full text pdf".
Ahab

Re: Tryptophan metabolism

Post by Ahab »

Kalastaja wrote:Oikealla suurin piirtein keskellä kohdan [EC] 2.1.1.49 jälkeen (joka edustaa indolietyyliamiini-N-metyylitransferaasia 'INMT', tunnetaan myös amiini metyylitransferaasina) olevasta N-metyylitryptamiinista
Mä näen tossa 2.1.1.49 perässä N-Methylserotonin. ?
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Touchet
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Joined: Fri 18 May 2007, 14:45

Re: Tryptophan metabolism

Post by Touchet »

Ahab wrote:
Kalastaja wrote:Oikealla suurin piirtein keskellä kohdan [EC] 2.1.1.49 jälkeen (joka edustaa indolietyyliamiini-N-metyylitransferaasia 'INMT', tunnetaan myös amiini metyylitransferaasina) olevasta N-metyylitryptamiinista
Mä näen tossa 2.1.1.49 perässä N-Methylserotonin. ?
Seuraa reittiä tryptofaanista kaakkoon 4.1.1.28:n (aromaattisten levoaminohappojen dekarboksylaatio) kautta tryptamiiniin ja siitä edelleen 2.1.1.49:sta (amiinien metyylitransferaasi) NMT:iin.

Navigoitava kartta täällä: http://www.genome.jp/dbget-bin/www_bget?pathway+ko00380
Softaa täällä: http://www.genome.jp/download/ (KegDraw on kiva lelu.)
"Jos ihmismieli on ihmeellisin asia mitä maa päällään kantaa, pyrkimys tutkia narkoottisten ja stimuloivien aineiden psykofysiologisen vaikutuksen syvyyksiä saa tämän ihmeen vaikuttamaan vieläkin suuremmalta."
— Professori Louis Lewin, 1924
Kalastaja

Re: Tryptophan metabolism

Post by Kalastaja »

Ahab wrote:
Kalastaja wrote:Oikealla suurin piirtein keskellä kohdan [EC] 2.1.1.49 jälkeen (joka edustaa indolietyyliamiini-N-metyylitransferaasia 'INMT', tunnetaan myös amiini metyylitransferaasina) olevasta N-metyylitryptamiinista
Mä näen tossa 2.1.1.49 perässä N-Methylserotonin. ?
Noi numerot vastaa jotain entsyymiä, entsyymireaktiota tai vastaavaa. Lähtöaineista tulee reaktion jälkeen jotain muuta.

Esim. N-metyyli-tryptamiini -> reagoi INMT:n [2.1.1.49] kanssa -> N,N-dimetyyli-tryptamiini.