Editing N,N-Dimethyltryptamine (section)

===Biosynthesis===
[[Image:DMT biosynthetic pathway.png|class=skin-invert-image|thumb|left|Biosynthetic pathway for ''N'',''N''-dimethyltryptamine]]

Dimethyltryptamine is an [[indole alkaloid]] derived from the [[shikimate]] pathway. Its [[biosynthesis]] is relatively simple and summarized in the adjacent picture. In plants, the parent amino acid [[L-tryptophan|{{sc|L}}-tryptophan]] is produced endogenously where in animals {{sc|L}}-tryptophan is an [[essential amino acid]] coming from diet. No matter the source of {{sc|L}}-tryptophan, the biosynthesis begins with its [[decarboxylation]] by an [[aromatic amino acid decarboxylase]] (AADC) [[enzyme]] (step 1). The resulting decarboxylated tryptophan [[Analog (chemistry)|analog]] is [[tryptamine]]. Tryptamine then undergoes a [[transmethylation]] (step 2): the enzyme [[tryptamine-N-methyltransferase|indolethylamine-''N''-methyltransferase]] (INMT) [[Catalysis|catalyzes]] the transfer of a [[methyl group]] from [[Cofactor (biochemistry)|cofactor]] [[S-adenosyl-methionine|''S''-adenosylmethionine]] (SAM), via [[nucleophilic]] attack, to tryptamine. This reaction transforms SAM into [[S-adenosylhomocysteine|''S''-adenosylhomocysteine]] (SAH), and gives the intermediate product [[N-methyltryptamine|''N''-methyltryptamine]] (NMT).<ref name="pmid13685339">{{cite journal | vauthors = Axelrod J | title = Enzymatic formation of psychotomimetic metabolites from normally occurring compounds | journal = Science | volume = 134 | issue = 3475 | page = 343 | date = August 1961 | pmid = 13685339 | doi = 10.1126/science.134.3475.343 | bibcode = 1961Sci...134..343A | s2cid = 39122485 }}</ref><ref name="pmid779022">{{cite journal | vauthors = Rosengarten H, Friedhoff AJ | title = A review of recent studies of the biosynthesis and excretion of hallucinogens formed by methylation of neurotransmitters or related substances | journal = Schizophrenia Bulletin | volume = 2 | issue = 1 | pages = 90–105 | year = 1976 | pmid = 779022 | doi = 10.1093/schbul/2.1.90 | doi-access = free }}</ref> NMT is in turn transmethylated by the same process (step 3) to form the end product ''N'',''N''-dimethyltryptamine. Tryptamine transmethylation is regulated by two products of the reaction: SAH,<ref name="pmid6792104">{{Cite book | vauthors = Barker SA, Monti JA, Christian ST |title=International Review of Neurobiology Volume 22 |chapter=N,N-Dimethyltryptamine: An Endogenous Hallucinogen |volume=22 |pages=83–110 |year=1981 |pmid=6792104 |doi=10.1016/S0074-7742(08)60291-3 |isbn=978-0-12-366822-6}}</ref><ref name="pmid4756800">{{cite journal | vauthors = Lin RL, Narasimhachari N, Himwich HE | title = Inhibition of indolethylamine-''N''-methyltransferase by ''S''-adenosylhomocysteine | journal = Biochemical and Biophysical Research Communications | volume = 54 | issue = 2 | pages = 751–759 | date = September 1973 | pmid = 4756800 | doi = 10.1016/0006-291X(73)91487-3 }}</ref><ref name="pmid9852119">{{cite journal | vauthors = Thompson MA, Weinshilboum RM | title = Rabbit lung indolethylamine ''N''-methyltransferase. cDNA and gene cloning and characterization | journal = The Journal of Biological Chemistry | volume = 273 | issue = 51 | pages = 34502–34510 | date = December 1998 | pmid = 9852119 | doi = 10.1074/jbc.273.51.34502 | doi-access = free }}</ref> and DMT<ref name="pmid6792104" /><ref name="pmid9852119" /> were shown ''ex vivo'' to be among the most potent inhibitors of rabbit INMT activity.

This transmethylation mechanism has been repeatedly and consistently proven by [[Isotope labeling|radiolabeling]] of SAM methyl group with [[carbon-14]] ((<sup>14</sup>C-CH<sub>3</sub>)SAM).<ref name="pmid13685339" /><ref name="pmid6792104" /><ref name="pmid9852119" /><ref name="pmid14361">{{cite journal | vauthors = Mandel LR, Prasad R, Lopez-Ramos B, Walker RW | title = The biosynthesis of dimethyltryptamine in vivo | journal = Research Communications in Chemical Pathology and Pharmacology | volume = 16 | issue = 1 | pages = 47–58 | date = January 1977 | pmid = 14361 }}</ref><ref name="pmid10552930">{{cite journal | vauthors = Thompson MA, Moon E, Kim UJ, Xu J, Siciliano MJ, Weinshilboum RM | title = Human indolethylamine ''N''-methyltransferase: cDNA cloning and expression, gene cloning, and chromosomal localization | journal = Genomics | volume = 61 | issue = 3 | pages = 285–297 | date = November 1999 | pmid = 10552930 | doi = 10.1006/geno.1999.5960 | url = http://crfdl.org:1111/xmlui/bitstream/handle/123456789/307/Thompson99humanINMT.pdf?sequence=1 | format = PDF }}{{dead link|date=March 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>