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|Section2= }} Harmine, also known as telepathine, is a fluorescent harmala alkaloid belonging to the beta-carboline family of compounds. It occurs in a number of different plants, most notably the Middle Eastern plant harmal or Syrian rue (''Peganum harmala'') and the South American vine ''Banisteriopsis caapi'' (also known as "yage" or "ayahuasca"). Harmine reversibly inhibits monoamine oxidase A (MAO-A), an enzyme which breaks down monoamines, making it a RIMA. Harmine selectively binds to MAO-A but does not inhibit the variant MAO-B.〔(Abstract Gerardy J, "Effect of moclobemide on rat brain monoamine oxidase A and B: comparison with harmaline and clorgyline.", Department of Pharmacology, University of Liège, Sart Tilman, Belgium. )〕 == Biosynthesis == Isolated from the plant ''Peganum Harmala'', harmine is an indole alkaloid with the pyrido()indole ring structure that is characteristic of the β-carboline alkaloids. The β-carboline alkaloids include as harmine, harmaline, harman and harmalol. These molecules are heterocyclic amines, biosynthesized through the combination of five- and six-membered ring structures that are derived from an amino acid- either L-tryptophan or tryptamine- which facilitates the formation of an indole ring system.〔Wernicke, Catrin, and Jochen Lehmann. "Beta-Carbolines: Occurrence, Biosynthesis, and Biodegredation." By Hans Rommelspacher.〕 The coincident occurrence of β-carboline alkaloids and serotonin in P. ''harmala'' indicates the presence of two very similar, interrelated biosynthetic pathways, which makes it difficult to definitively identify whether free tryptamine or L-tryptophan is the precursor to the biosynthesis of harmine.〔Berlin, Jochen, Christiane Rugenhagen, Norbert Greidziak, Inna Kuzovkina, Ludger Witte, and Victor Wray. "Biosynthesis of Serotonin and Beta-carboline Alkaloids in Hairy Root Cultures of Peganum Harmala." ''Phytochemistry'' 33.3 (1993): 593-97.〕 However, it is postulated that L-tryptophan is the most likely precursor, with tryptamine existing as an intermediate in the pathway. The following figure shows the proposed biosynthetic scheme for harmine.〔Nettleship, Lesley, and Michael Slaytor. "Limitations of Feeding Experiments in Studying Alkaloid Biosynthesis in Peganum Harmala Callus Cultures."''Phytochemistry'' 13.4 (1974): 735-42.〕 The Shikimate acid pathway yields the aromatic amino acid, L-tryptophan. Decarboxylation of L-tryptophan by aromatic L-amino acid decarboxylase (AADC) produces tryptamine (I), which contains a nucleophilic center at the C-2 carbon of the indole ring due to the adjacent nitrogen atom that enables the participation in a mannich-type reaction. Rearrangements enable the formation of a Schiff base from tryptamine, which then reacts with pyruvate in II to form a β-carboline carboxylic acid. The β-carboline carboxylic acid subsequently undergoes decarboxylation to produce 1-methyl β-carboline III. Hydroxylation followed by methylation in IV yields harmaline. The order of O-methylation and hydroxylation have been shown to be inconsequential to the formation of the harmaline intermediate.〔 In the last step V, the oxidation of harmaline is accompanied by the loss of water and effectively generates harmine. The difficulty distinguishing between L-tryptophan and free tryptamine as the precursor of harmine biosynthesis originates from the presence of the serotonin biosynthetic pathway, which closely resembles that of harmine, yet necessitates the availability of free tryptamine as its precursor.〔 As such, it is unclear if the decarboxylation of L-tryptophan, or the incorporation of pyruvate into the basic tryptamine structure is the first step of harmine biosynthesis. However, feeding experiments involving the feeding of one of tryptamine to hairy root cultures of P. ''harmala'' showed that the feeding of tryptamine yielded a great increase in serotonin levels with little to no effect on β-carboline levels, confirming that tryptamine is the precursor for serotonin, and indicating that it is likely only an intermediate in the biosynthesis of harmine otherwise comparable increases in harmine levels would have been observed.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「harmine」の詳細全文を読む スポンサード リンク
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