Editing Capsaicin (section)

==Biosynthesis==
[[File:BhutJolokia09 Asit.jpg|thumb|Chili peppers]]
[[Image:Vanillamine biosynthesis.gif|class=skin-invert-image|thumb|Vanillamine is a product of the phenylpropanoid pathway.]]
[[Image:8-methyl-6-nonenoyl biosynthesis.gif|class=skin-invert-image|thumb|Valine enters the branched fatty acid pathway to produce 8-methyl-6-nonenoyl-CoA.]]
[[Image:Condensation to capsaicin.gif|class=skin-invert-image|thumb|Capsaicin synthase condenses vanillamine and 8-methyl-6-nonenoyl-CoA to produce capsaicin.]]

=== History ===
The general biosynthetic pathway of capsaicin and other capsaicinoids was elucidated in the 1960s by Bennett and Kirby, and Leete and Louden. Radiolabeling studies identified phenylalanine and valine as the precursors to capsaicin.<ref>Bennett DJ, Kirby GW (1968) Constitution and biosynthesis of capsaicin. J Chem Soc C 4:442–446</ref><ref name="Leete, E. 1968"/> Enzymes of the [[phenylpropanoid]] pathway, phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), caffeic acid ''O''-methyltransferase (COMT) and their function in capsaicinoid biosynthesis were identified later by Fujiwake et al.,<ref>{{cite journal | vauthors = Fujiwake H, Suzuki T, Iwai K | title = Intracellular distributions of enzymes and intermediates involved in biosynthesis of capsaicin and its analogues in Capsicum fruits. | journal = Agricultural and Biological Chemistry | date = November 1982 | volume = 46 | issue = 11 | pages = 2685–2689 | doi = 10.1080/00021369.1982.10865495 }}</ref><ref>{{cite journal | vauthors = Fujiwake H, Suzuki T, Iwai K | title = Capsaicinoid formation in the protoplast from the placenta of Capsicum fruits. | journal = Agricultural and Biological Chemistry | date = October 1982 | volume = 46 | issue = 10 | pages = 2591–2592 | doi = 10.1080/00021369.1982.10865477 }}</ref> and Sukrasno and Yeoman.<ref>{{cite journal | vauthors = Sukrasno N, Yeoman MM | year = 1993 | title = Phenylpropanoid metabolism during growth and development of ''Capsicum frutescens'' fruits | journal = Phytochemistry | volume = 32 | issue = 4| pages = 839–844 | doi=10.1016/0031-9422(93)85217-f| bibcode = 1993PChem..32..839S }}</ref> Suzuki et al. are responsible for identifying leucine as another precursor to the branched-chain [[Fatty acid synthesis|fatty acid pathway]].<ref>{{cite journal | vauthors = Suzuki T, Kawada T, Iwai K | year = 1981 | title = Formation and metabolism of pungent principle of ''Capsicum'' fruits. 9. Biosynthesis of acyl moieties of capsaicin and its analogs from valine and leucine in ''Capsicum'' fruits | journal = Plant & Cell Physiology | volume = 22 | pages = 23–32 | doi = 10.1093/oxfordjournals.pcp.a076142 }}</ref> It was discovered in 1999 that pungency of chili peppers is related to higher transcription levels of key enzymes of the phenylpropanoid pathway, phenylalanine ammonia lyase, cinnamate 4-hydroxylase, caffeic acid ''O''-methyltransferase. Similar studies showed high transcription levels in the placenta of chili peppers with high pungency of genes responsible for branched-chain fatty acid pathway.<ref>{{cite journal | vauthors = Curry J, Aluru M, Mendoza M, Nevarez J, Melendrez M, O'Connell MA | year = 1999 | title = Transcripts for possible capsaicinoid biosynthetic genes are differentially accumulated in pungent and non-pungent ''Capsicum'' spp | journal = Plant Sci | volume = 148 | issue = 1 | pages = 47–57 | doi = 10.1016/s0168-9452(99)00118-1 | bibcode = 1999PlnSc.148...47C | s2cid = 86735106 }}</ref>

===Biosynthetic pathway===
Plants exclusively of the genus ''[[Capsicum]]'' produce capsaicinoids, which are [[alkaloid]]s.<ref>{{cite journal|vauthors=Nelson EK, Dawson LE|title=Constitution of capsaicin, the pungent principle of ''Capsicum''. III|journal=J Am Chem Soc|date=1923|volume=45|issue=9|pages=2179–2181|doi=10.1021/ja01662a023|bibcode=1923JAChS..45.2179N }}</ref>  Capsaicin is believed to be synthesized in the [[Locule|interlocular]] [[septum#Botany|septum]] of chili peppers and depends on the gene ''AT3'', which resides at the ''pun1'' [[Locus (genetics)|locus]], and which encodes a putative [[acyltransferase]].<ref>{{cite journal | vauthors = Stewart C, Kang BC, Liu K, Mazourek M, Moore SL, Yoo EY, Kim BD, Paran I, Jahn MM | title = The Pun1 gene for pungency in pepper encodes a putative acyltransferase | journal = The Plant Journal | volume = 42 | issue = 5 | pages = 675–688 | date = June 2005 | pmid = 15918882 | doi = 10.1111/j.1365-313X.2005.02410.x | title-link = doi | doi-access = free }}</ref>

Biosynthesis of the capsaicinoids occurs in the glands of the pepper fruit where capsaicin synthase condenses [[vanillylamine]] from the [[phenylpropanoid]] pathway with an acyl-CoA moiety produced by the branched-chain [[Fatty acid synthesis|fatty acid pathway]].<ref name="Leete, E. 1968">{{cite journal | vauthors = Leete E, Louden MC | title = Biosynthesis of capsaicin and dihydrocapsaicin in Capsicum frutescens | journal = Journal of the American Chemical Society | volume = 90 | issue = 24 | pages = 6837–6841 | date = November 1968 | pmid = 5687710 | doi = 10.1021/ja01026a049 | bibcode = 1968JAChS..90.6837L }}</ref><ref name="Bennett, D.J. 1968">{{cite journal | vauthors = Bennett DJ, Kirby GW | year = 1968 | title = Constitution and biosynthesis of capsaicin | journal = J. Chem. Soc. C | volume = 1968 | pages = 442–446 | doi = 10.1039/j39680000442 }}</ref><ref>{{cite journal | vauthors = Fujiwake H, Suzuki T, Oka S, Iwai K | year = 1980 | title = Enzymatic formation of capsaicinoid from vanillylamine and iso-type fatty acids by cell-free extracts of ''Capsicum annuum'' var. ''annuum'' cv. Karayatsubusa | journal = Agricultural and Biological Chemistry | volume = 44 | issue = 12| pages = 2907–2912 | doi=10.1271/bbb1961.44.2907| doi-access = free | title-link=doi }}</ref><ref>{{cite book | vauthors = Guzman I, Bosland PW, O'Connell MA | chapter = Chapter 8: Heat, Color, and Flavor Compounds in ''Capsicum'' Fruit | veditors = Gang DR | title = Recent Advances in Phytochemistry 41: The Biological Activity of Phytochemicals | location = New York, New York | publisher =  Springer | date = 2011 | chapter-url = https://books.google.com/books?id=--nQIHiE3QwC&pg=PA117 | pages = 117–118 | isbn = 9781441972996 }}</ref>

Capsaicin is the most abundant capsaicinoid found in the genus ''[[Capsicum]]'', but at least ten other capsaicinoid variants exist.<ref>{{cite journal | vauthors = Kozukue N, Han JS, Kozukue E, Lee SJ, Kim JA, Lee KR, Levin CE, Friedman M | title = Analysis of eight capsaicinoids in peppers and pepper-containing foods by high-performance liquid chromatography and liquid chromatography-mass spectrometry | journal = Journal of Agricultural and Food Chemistry | volume = 53 | issue = 23 | pages = 9172–9181 | date = November 2005 | pmid = 16277419 | doi = 10.1021/jf050469j }}</ref> Phenylalanine supplies the precursor to the [[phenylpropanoid pathway]] while leucine or valine provide the precursor for the branched-chain fatty acid pathway.<ref name="Leete, E. 1968"/><ref name="Bennett, D.J. 1968"/> To produce capsaicin, 8-methyl-6-nonenoyl-CoA is produced by the branched-chain fatty acid pathway and condensed with vanillylamine. Other capsaicinoids are produced by the condensation of vanillylamine with various acyl-CoA products from the branched-chain fatty acid pathway, which is capable of producing a variety of acyl-CoA moieties of different chain length and degrees of unsaturation.<ref>{{cite journal | vauthors = Thiele R, Mueller-Seitz E, Petz M | title = Chili pepper fruits: presumed precursors of fatty acids characteristic for capsaicinoids | journal = Journal of Agricultural and Food Chemistry | volume = 56 | issue = 11 | pages = 4219–4224 | date = June 2008 | pmid = 18489121 | doi = 10.1021/jf073420h | bibcode = 2008JAFC...56.4219T }}</ref> All condensation reactions between the products of the phenylpropanoid and branched-chain fatty acid pathway are mediated by capsaicin synthase to produce the final capsaicinoid product.<ref name="Leete, E. 1968"/><ref name="Bennett, D.J. 1968"/>