Editing Nicotine (section)

===Biosynthesis===
[[File:Nicotine biosynthesis june 2012.png|thumb|300px|class=skin-invert-image|Nicotine biosynthesis]]
The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that comprise nicotine. Metabolic studies show that the [[pyridine]] ring of nicotine is derived from [[nicotinic acid]] the [[pyrrolidine]] is derived from ''N''-methyl-Δ<sup>1</sup>-pyrrollidium cation.<ref>{{cite journal | vauthors = Lamberts BL, Dewey LJ, Byerrum RU | title = Ornithine as a precursor for the pyrrolidine ring of nicotine | journal = Biochimica et Biophysica Acta | volume = 33 | issue = 1 | pages = 22–6 | date = May 1959 | pmid = 13651178 | doi = 10.1016/0006-3002(59)90492-5 }}</ref><ref>{{cite journal |doi=10.1021/ja01495a059 |title=The Biosynthesis of Nicotine from Isotopically Labeled Nicotinic Acids |year=1960 |vauthors=Dawson RF, Christman DR, d'Adamo A, Solt ML, Wolf AP |journal=Journal of the American Chemical Society |volume=82 |issue=10 |pages=2628–2633|bibcode=1960JAChS..82.2628D }}</ref> Biosynthesis of the two component structures proceeds via two independent syntheses, the NAD pathway for nicotinic acid and the tropane pathway for ''N''-methyl-Δ<sup>1</sup>-pyrrollidium cation.

The NAD pathway in the genus ''[[Nicotiana]]'' begins with the oxidation of aspartic acid into α-amino succinate by aspartate oxidase (AO). This is followed by a condensation with [[glyceraldehyde-3-phosphate]] and a cyclization catalyzed by quinolinate synthase (QS) to give [[quinolinic acid]]. Quinolinic acid then reacts with phosphoribosyl pyrophosphate catalyzed by quinolinic acid phosphoribosyl transferase (QPT) to form nicotinic acid mononucleotide (NaMN). The reaction now proceeds via the NAD salvage cycle to produce nicotinic acid via the conversion of [[nicotinamide]] by the enzyme [[nicotinamidase]].{{citation needed|date=May 2021}}

The ''N''-methyl-Δ<sup>1</sup>-pyrrollidium cation used in the synthesis of nicotine is an intermediate in the synthesis of tropane-derived alkaloids. Biosynthesis begins with [[decarboxylation]] of [[ornithine]] by [[ornithine decarboxylase]] (ODC) to produce [[putrescine]]. Putrescine is then converted into ''N''-methyl putrescine via [[methylation]] by SAM catalyzed by [[Putrescine N-methyltransferase|putrescine ''N''-methyltransferase]] (PMT). ''N''-methyl putrescine then undergoes [[deamination]] into 4-methylaminobutanal by the ''N''-methyl putrescine oxidase (MPO) enzyme, 4-methylaminobutanal then spontaneously cyclize into ''N''-methyl-Δ<sup>1</sup>-pyrrollidium cation.{{citation needed|date=May 2021}}

The final step in the synthesis of nicotine is the coupling between ''N''-methyl-Δ<sup>1</sup>-pyrrollidium cation and nicotinic acid. Although studies conclude some form of coupling between the two component structures, the definite process and mechanism remains undetermined. The current agreed theory involves the conversion of nicotinic acid into 2,5-dihydropyridine through 3,6-dihydronicotinic acid. The 2,5-dihydropyridine intermediate would then react with ''N''-methyl-Δ<sup>1</sup>-pyrrollidium cation to form [[enantiomer]]ically pure (−)-nicotine.<ref name=plant-meta>{{cite book | veditors = Ashihara H, Crozier A, Komamine A |title=Plant metabolism and biotechnology |date=7 June 2011 |publisher=Wiley |location=Cambridge |isbn=978-0-470-74703-2}}{{page needed|date=December 2013}}</ref>