Nicotine is the principal alkaloid in the leaves of commercially used tobacco (Nicotiana tabacum and N. rustica). Nicotine in tobacco leaves and in plant-derived preparations is mostly in the (S)-nicotine isomeric form. However, tobacco smoke contains up to 10% (R)-nicotine, probably due to racemization during combustion. Nicotine is the addictive compound in tobacco and is a commonly used psychoactive drug. It enters the body by systemic absorption through cigarette smoking, oral snuff, pipe tobacco, cigars and chewing tobacco use. It can also enter in purified form as a medication. Nicotine has complex physiological effects. In cigarette smoke nicotine is carried into the body on particulate matter. It is rapidly absorbed in the small airways and alveoli of the lung. In this neutral pH environment, it is un-ionized, soluble, and can be transferred across cell membranes and into the blood. It moves into the pulmonary venous circulation, to the left ventricle of the heart, and into the systemic arterial circulation. It travels to the brain within seconds where it binds to nicotinic cholinergic receptors and activates the dopaminergic reward system. Other forms of nicotine (such as nicotine gum, transdermal patch, inhaler, lozenges, and sublingual tablets) are usually buffered at alkaline pH and quickly traverse cell membranes, but most reach the blood and brain more slowly. They are less likely to cause addiction due to the delayed reward of nicotine effects. In humans, the primary site of nicotine metabolism is the liver. There is little evidence in the literature for any extrahepatic metabolism, despite the presence of isoforms of nicotine metabolizing enzymes in other tissues. Nicotine and its metabolites are excreted in urine, where they have been analyzed and quantitated. These data showed considerable interindividual variability in the amount of each metabolite produced. Cotinine is the primary metabolite of nicotine and is found in the urine of smokers. In studies of nicotine metabolism in smokers, it has been estimated that 70% of a nicotine dose is metabolized to cotinine. It reaches high levels in the blood and has a long half-life. The cotinine metabolite trans-3'-hydroxycotinine is the most abundant metabolite in urine. Glucuronide conjugation is a significant route of nicotine metabolism, with nicotine, cotinine and trans-3'-hydroxycotinine glucuronides accounting for up to 30% of total metabolites recovered in urine. Website=http://biocyc.org/META/NEW-IMAGE?type 4.0 inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive Long Name: NADPH Synonym: Synonym not specified Accession: S06096 inside SIMPLE_MOLECULE NADPH Long Name: NADP+ Synonym: Synonym not specified Accession: S06077 inside SIMPLE_MOLECULE NADP_super__plus_ Long Name: cytochrome P450 subfamily IIA polypeptide 6 Synonym: Coumarin 7-hydroxylase Accession: P05984 inside PROTEIN pr1 Long Name: nicotine-_DELTA_1 5-iminium ion Synonym: Synonym not specified Accession: S06091 inside SIMPLE_MOLECULE nicotine-_DELTA__super_1 5_endsuper__minus_iminium ion Long Name: H2O Synonym: Synonym not specified Accession: S06097 inside SIMPLE_MOLECULE H_sub_2_endsub_O Long Name: 2-hydroxynicotine Synonym: Synonym not specified Accession: S06080 inside SIMPLE_MOLECULE 2_minus_hydroxynicotine Long Name: O2 Synonym: Synonym not specified Accession: S06100 inside SIMPLE_MOLECULE O_sub_2_endsub_ Long Name: Aldehyde oxidase 1 Synonym: Synonym not specified Accession: P05983 inside PROTEIN pr2 Long Name: H2O2 Synonym: Synonym not specified Accession: S06094 inside SIMPLE_MOLECULE H_sub_2_endsub_O_sub_2_endsub_ Long Name: cotinine Synonym: Synonym not specified Accession: S06086 inside SIMPLE_MOLECULE cotinine Long Name: 4-(methylamino)-1-(3-pyridyl)-1-butanone Synonym: Synonym not specified Accession: S06098 inside SIMPLE_MOLECULE 4-(methylamino)-1-(3-pyridyl)-1-butanone Long Name: formaldehyde Synonym: Synonym not specified Accession: S06089 inside SIMPLE_MOLECULE formaldehyde Long Name: 4-oxo-4-(3-pyridyl)-butanamide Synonym: Synonym not specified Accession: S06075 inside SIMPLE_MOLECULE 4-oxo-4-(3-pyridyl)-butanamide Long Name: 4-oxo-4-(3-pyridyl)-butanoate Synonym: Synonym not specified Accession: S06095 inside SIMPLE_MOLECULE 4-oxo-4-(3-pyridyl)-butanoate Long Name: nornicotine Synonym: Synonym not specified Accession: S06069 inside SIMPLE_MOLECULE nornicotine Long Name: norcotine Synonym: Synonym not specified Accession: S06083 inside SIMPLE_MOLECULE norcotine Long Name: 4-hydroxy-4-(3-pyridyl)-butanoate Synonym: Synonym not specified Accession: S06088 inside SIMPLE_MOLECULE 4-hydroxy-4-(3-pyridyl)-butanoate Long Name: nicotine Synonym: Synonym not specified Accession: S06084 inside SIMPLE_MOLECULE nicotine Long Name: S-adenosyl-homocysteine Synonym: Synonym not specified Accession: S06082 inside SIMPLE_MOLECULE S_minus_adenosyl_minus__br_homocysteine Long Name: S-adenosyl-L-methionine Synonym: Synonym not specified Accession: S06073 inside SIMPLE_MOLECULE S_minus_adenosyl_minus_L_minus__br_methionine Long Name: nicotine isomethonium ion Synonym: Synonym not specified Accession: S06070 inside SIMPLE_MOLECULE nicotine isomethonium ion Long Name: 4-(3-pyridyl)-3-butanoate Synonym: Synonym not specified Accession: S06099 inside SIMPLE_MOLECULE 4-(3-pyridyl)-3-butanoate Long Name: indolethylamine N-methyltransferase Synonym: Synonym not specified Accession: P05981 inside PROTEIN pr3 Long Name: 4-(3-pyridyl)-butanoate Synonym: Synonym not specified Accession: S06103 inside SIMPLE_MOLECULE 4-(3-pyridyl)-butanoate Long Name: nicotine-1-N-oxide Synonym: Synonym not specified Accession: S06074 inside SIMPLE_MOLECULE nicotine_minus_1_minus_N_minus_oxide Long Name: 3-pyridylacetate Synonym: Synonym not specified Accession: S06092 inside SIMPLE_MOLECULE 3-pyridylacetate Long Name: Flavin-containing monooxygenase Synonym: Dimethylaniline N-oxidase,Dimethylaniline monooxygenase (N-oxide-forming) Accession: P05979 inside PROTEIN pr4 Long Name: UDP-D-glucuronate Synonym: Synonym not specified Accession: S06101 inside SIMPLE_MOLECULE UDP_minus_D_minus_glucuronate Long Name: UDP Synonym: Synonym not specified Accession: S06079 inside SIMPLE_MOLECULE UDP Long Name: nicotine-glucuronide Synonym: Synonym not specified Accession: S06102 inside SIMPLE_MOLECULE nicotine_minus_glucuronide Long Name: UDP glycosytransferase 1, polypeptide A4 Synonym: Synonym not specified Accession: P05982 inside PROTEIN pr5 Long Name: trans-3'-hydroxycotinine Synonym: Synonym not specified Accession: S06085 inside SIMPLE_MOLECULE trans-3'-hydroxycotinine Long Name: UDP glycosyltransferase 2, member B7 Synonym: uridine diphosphate glycosyltransferase 2, member B7 Accession: P05980 inside PROTEIN pr6 Long Name: trans-3'-hydroxycotinine N-glucuronide Synonym: Synonym not specified Accession: S06068 inside SIMPLE_MOLECULE trans_minus_3'_minus_hydroxycotinine_br_N_minus_glucuronide Long Name: trans-3'-hydroxycotinine O-glucuronide Synonym: Synonym not specified Accession: S06090 inside SIMPLE_MOLECULE trans_minus_3'_minus_hydroxycotinine_br_O_minus_glucuronide Long Name: 4-oxo-4-(3-pyridyl)-N-methylbutanamide Synonym: Synonym not specified Accession: S06081 inside SIMPLE_MOLECULE 4-oxo-4-(3-pyridyl)-_br_N-methylbutanamide Long Name: 5'-hydroxycotinine Synonym: Synonym not specified Accession: S06071 inside SIMPLE_MOLECULE 5'-hydroxycotinine Long Name: cotinine N-oxide Synonym: Synonym not specified Accession: S06087 inside SIMPLE_MOLECULE cotinine N-oxide Long Name: cotinine methonium ion Synonym: Synonym not specified Accession: S06093 inside SIMPLE_MOLECULE cotinine methonium ion Long Name: cotinine-glucuronide Synonym: Synonym not specified Accession: S06078 inside SIMPLE_MOLECULE cotinine-glucuronide Long Name: N-hydroxymethyl-norcotinine Synonym: Synonym not specified Accession: S06076 inside SIMPLE_MOLECULE N-hydroxymethyl-norcotinine Long Name: norcotinine Synonym: Synonym not specified Accession: S06072 inside SIMPLE_MOLECULE norcotinine STATE_TRANSITION 0.972777791930306,0.13862389324844349 0.9796398102372623,0.10340014596729685 0.9905695527154164,0.04331669623228429 sa25 sa1 sa4 sa2 sa3 STATE_TRANSITION 0.11469613409769952,-0.003975001096703679 0.4602365311106065,-0.004779863096257664 sa4 sa5 sa7 sa63 sa10 sa8 STATE_TRANSITION 0.401539451472283,0.2560667176105804 0.6065742701688712,0.16710173873299272 0.8331330329334408,0.07281395759356624 sa25 sa27 sa28 sa26 sa30 STATE_TRANSITION 0.6947484777452502,-0.32868862499973694 0.763933821462973,-0.25416255091883055 0.9329597765878992,-0.07056743093578843 sa25 sa33 sa34 sa36 sa32 sa35 sa38 STATE_TRANSITION 0.8180425572015877,-0.33140688369972726 0.879390197016741,-0.21402522463802587 0.9416414111811213,-0.09979607922951361 sa25 sa39 sa41 sa40 sa42 STATE_TRANSITION 0.835363634185426,0.31774559045091144 0.8824761363425799,0.2268192040387904 0.9486952089381435,0.0987354043852442 sa25 sa12 sa9 sa6 sa13 sa11 sa3 UNKNOWN_TRANSITION sa6 sa15 UNKNOWN_TRANSITION 0.6219627000167387,-0.2856300568077108 0.7689111941860007,-0.17768551232307317 sa25 sa18 sa21 sa16 UNKNOWN_TRANSITION 0.6685991481306202,-0.00828206341693516 sa21 sa19 sa22 UNKNOWN_TRANSITION sa22 sa17 UNKNOWN_TRANSITION sa17 sa20 UNKNOWN_TRANSITION sa15 sa20 UNKNOWN_TRANSITION sa20 sa24 UNKNOWN_TRANSITION sa24 sa29 UNKNOWN_TRANSITION sa29 sa31 UNKNOWN_TRANSITION sa31 sa37 STATE_TRANSITION 0.8687143977696121,0.25667446431160523 0.9132439014197236,0.1757961117725797 0.9795505515277191,0.0415082155958546 sa63 sa43 sa46 sa47 sa44 sa45 sa51 STATE_TRANSITION 0.7349498867991604,0.3294680823278995 sa63 sa55 sa58 sa60 sa56 sa57 sa51 STATE_TRANSITION sa60 sa59 STATE_TRANSITION 0.6487902333218037,0.12626671814482204 sa63 sa61 STATE_TRANSITION 0.7516382420715608,-0.14782026063591713 sa63 sa67 STATE_TRANSITION 0.7628428904367515,-0.2546714017143007 0.8340917968946435,-0.17395362267500836 0.9330934455390376,-0.07134057118018744 sa63 sa68 sa70 sa69 sa71 STATE_TRANSITION 0.881172922695548,-0.23304032846622016 0.9132367292280825,-0.16963379198861542 0.9768867962899084,-0.045328966315530315 sa63 sa77 sa79 sa75 sa76 sa78 sa85 STATE_TRANSITION 0.22572356763142398,0.0 0.7854991139988181,-3.544004725331007E-4 sa75 sa81 sa83 sa84 sa80 sa82 sa85 UNKNOWN_TRANSITION 0.11767280974196792,0.317127021790101 sa59 sa66 UNKNOWN_TRANSITION sa66 sa64 UNKNOWN_TRANSITION sa64 sa65 UNKNOWN_TRANSITION sa65 sa73 UNKNOWN_TRANSITION sa73 sa72 UNKNOWN_TRANSITION sa84 sa74 UNKNOWN_TRANSITION sa74 sa66 STATE_TRANSITION sa47 sa52 sa48 STATE_TRANSITION 0.29266851050541964,0.004193246197082279 0.7010639247000046,-0.012981219610117556 sa47 sa50 sa53 sa54 sa49