284PathwayHeroin Metabolism PathwayHeroin is a mu-opioid agonist. It acts on endogenous mu-opioid receptors that are spread in discrete packets throughout the brain, spinal cord and gut in almost all mammals. Heroin, along with other opioids, are agonists to four endogenous neurotransmitters. They are beta-endorphin, dynorphin, leu-enkephalin, and met-enkephalin. The body responds to heroin in the brain by reducing (and sometimes stopping) production of the endogenous opioids when heroin is present. Endorphins are regularly released in the brain and nerves, attenuating pain.Drug MetabolismPW000599CenterPathwayVisualizationContext66917002600#000099PathwayVisualization313284Heroin PathwayHeroin is a mu-opioid agonist. It acts on endogenous mu-opioid receptors that are spread in discrete packets throughout the brain, spinal cord and gut in almost all mammals. Heroin, along with other opioids, are agonists to four endogenous neurotransmitters. They are beta-endorphin, dynorphin, leu-enkephalin, and met-enkephalin. The body responds to heroin in the brain by reducing (and sometimes stopping) production of the endogenous opioids when heroin is present. Endorphins are regularly released in the brain and nerves, attenuating pain.Drug1633Morphine activation of Mu-type opioid receptorActivatingSubPathway10598829Compound371060254ProteinComplex73137716778732Maurer HH, Sauer C, Theobald DS: Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine. Ther Drug Monit. 2006 Jun;28(3):447-53. doi: 10.1097/01.ftd.0000211812.27558.6e.284Pathway1378Opioids. (2009). e-CPS (online version of Compendium of Pharmaceuticals and Specialties). Retrieved October 25, 2009.284Pathway1CellCL:00000003NeuronCL:00005405HepatocyteCL:00001824Cardiomyocyte CL:00007467Epithelial CellCL:00000661Homo sapiens9606EukaryoteHuman2Bacteria2ProkaryoteBacteria3Escherichia coli562Prokaryote12Mus musculus10090EukaryoteMouse5Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat19Schizosaccharomyces pombe4896Eukaryote24Solanum lycopersicum4081EukaryoteTomato4Arabidopsis thaliana3702EukaryoteThale cress18Saccharomyces cerevisiae4932EukaryoteYeast21Xenopus laevis8355EukaryoteAfrican clawed frog6Caenorhabditis elegans6239EukaryoteRoundworm25Escherichia coli (strain K12)83333Prokaryote49Bathymodiolus platifrons220390EukaryoteDeep sea mussel10Drosophila melanogaster7227EukaryoteFruit fly23Pseudomonas aeruginosa287Prokaryote60Nitzschia sp.0001EukaryoteNitzschia48Smooth Endoplasmic Reticulum GO:000579011Extracellular SpaceGO:000561521SynapseGO:00452027Endoplasmic Reticulum MembraneGO:00057895CytoplasmGO:000573720Endoplasmic Reticulum LumenGO:00057881CytosolGO:00058296LysosomeGO:00057644PeroxisomeGO:00057773Mitochondrial MatrixGO:00057592MitochondrionGO:000573910Cell MembraneGO:000588616Lysosomal LumenGO:004320218Melanosome MembraneGO:003316213Endoplasmic ReticulumGO:000578325Golgi apparatusGO:000579414Mitochondrial Outer MembraneGO:000574112Mitochondrial Inner MembraneGO:000574315NucleusGO:000563431Periplasmic SpaceGO:000562035ChloroplastGO:000950736MembraneGO:001602053Endoplasmic Reticulum BodyGO:001016834Plant-Type VacuoleGO:000032540PeriplasmGO:004259722post-synaptic membraneGO:00452111LiverBTO:00007597297Nervous SystemBTO:00014844Adrenal MedullaBTO:000004971825IntestineBTO:000064828StomachBTO:0001307155268Blood VesselBTO:0001102741111HeartBTO:0000562731029111PW_BS000029111811PW_BS000011711113PW_BS0000713772113PW_BS000037101711PW_BS000010311511PW_BS00003115111PW_BS0000153612011PW_BS000036261115PW_BS0000268511PW_BS0000089611PW_BS0000095411PW_BS0000054311PW_BS0000043211PW_BS00000314101PW_BS00001413121PW_BS0000132811611PW_BS000028204111PW_BS000020331811PW_BS000033181311PW_BS0000182111PW_BS00000249711PW_BS000049541315PW_BS000054432511PW_BS0000432441011PW_BS000024221411PW_BS00002260251PW_BS00006046114PW_BS000046171211PW_BS0000177028511PW_BS00007072513PW_BS000072612517PW_BS00006193252011PW_BS00009327151PW_BS000027711PW_BS000007971521PW_BS000097100521PW_BS000100943PW_BS000094103331PW_BS000103105113PW_BS0001051115121PW_BS0001111136121PW_BS0001131122121PW_BS000112110231PW_BS0001101231751PW_BS0001231251351PW_BS000125126651PW_BS00012612711651PW_BS00012713013121PW_BS0001301141112PW_BS00011412915121PW_BS0001291355171PW_BS0001351181171PW_BS00011810813PW_BS0001086131PW_BS000006140103PW_BS000140101531PW_BS00010114315191PW_BS0001431465191PW_BS000146107313PW_BS000107951721PW_BS0000951471241PW_BS000147151141PW_BS0001511553241PW_BS0001551572241PW_BS0001571613181PW_BS0001611632181PW_BS00016315924PW_BS00015911PW_BS00000116611PW_BS0001661783211PW_BS0001781802211PW_BS00018015284PW_BS000152117131PW_BS000117188118PW_BS0000241601181PW_BS000160205561PW_BS000024207661PW_BS000024206261PW_BS0000242111018PW_BS0000242137181PW_BS00002421425181PW_BS0000242156181PW_BS0000241985181PW_BS0000242164181PW_BS00002421013181PW_BS00002421217181PW_BS000024222341PW_BS000024224241PW_BS0000241901118PW_BS00002417018PW_BS0001702253541PW_BS000024226441PW_BS00002416212181PW_BS0001622771218PW_BS0000241644PW_BS0001642811251PW_BS0000242851041PW_BS0000242863641PW_BS0000242875341PW_BS0000242491341PW_BS0000242273441PW_BS00002465111PW_BS0000652905491PW_BS0000242916491PW_BS0000242924491PW_BS00002429817101PW_BS00002430013101PW_BS0000243016101PW_BS000024302116101PW_BS0000242231241PW_BS0000242941141PW_BS0000243081011PW_BS000024315123PW_BS0000243183123PW_BS0000243221231PW_BS00002429341PW_BS000024253541PW_BS0000241321121PW_BS0001321333121PW_BS00013313412121PW_BS0001343317121PW_BS00002833217121PW_BS0000283331212PW_BS0000281151012PW_BS0001153344121PW_BS0000283361121PW_BS000028337116121PW_BS00002834141121PW_BS00002834318121PW_BS00002834713125PW_BS00002832914121PW_BS0000283522512PW_BS00002835325127PW_BS00002835625121PW_BS000028360410121PW_BS0000283683601PW_BS0000283702601PW_BS000028228361PW_BS0000241192171PW_BS000119383751PW_BS0001003841251PW_BS000100390761PW_BS0001123911261PW_BS0001123987171PW_BS000113232403PW_BS000024122551PW_BS000122406351PW_BS000115407251PW_BS000115408451PW_BS000115124151PW_BS000124412125PW_BS000115405105PW_BS000115409115PW_BS0001154151851PW_BS0001154141551PW_BS0001154251355PW_BS000115429151PW_BS00011512112171PW_BS0001214192551PW_BS00011543441051PW_BS0001153821451PW_BS000100436255PW_BS0001151203171PW_BS0001203744171PW_BS0000534436171PW_BS0001154461217PW_BS0001153761017PW_BS0000531371117PW_BS00013744717171PW_BS00011513613171PW_BS000136448116171PW_BS00011545118171PW_BS00011545015171PW_BS00011546013175PW_BS0001154641171PW_BS00011545525171PW_BS000115469410171PW_BS00011539914171PW_BS0001134712517PW_BS00011547225177PW_BS0001152975101PW_BS0000244793101PW_BS0001154812101PW_BS0001154824101PW_BS0001152991101PW_BS0000244831110PW_BS0001154781010PW_BS00011548718101PW_BS00011549025101PW_BS0001154957101PW_BS00011548414101PW_BS00011548012101PW_BS000115501361PW_BS000115502461PW_BS000115388161PW_BS000112208116PW_BS000024209106PW_BS0000245041861PW_BS0001155072561PW_BS00011551541061PW_BS0001153891461PW_BS0001123951361PW_BS0001135131761PW_BS0001153872213PW_BS000038731013PW_BS0000737413PW_BS0000747725111PW_BS000077225976-AcetylmorphineHMDB00418126-acetylmorphine belongs to the family of Morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic.2784-73-8C11781520352453890CN1CCC23C4OC5=C(O)C=CC(CC1C2C=CC4OC(C)=O)=C35C19H21NO4InChI=1S/C19H21NO4/c1-10(21)23-15-6-4-12-13-9-11-3-5-14(22)17-16(11)19(12,18(15)24-17)7-8-20(13)2/h3-6,12-13,15,18,22H,7-9H2,1-2H3JJGYGPZNTOPXGV-UHFFFAOYSA-N10-hydroxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10,15-tetraen-14-yl acetate327.3743327.147058165-2.46110-hydroxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10,15-tetraen-14-yl acetate016-mam;6-monoacetylmorphine;6-o-acetylmorphine;6-o-monoacetylmorphine;Monoacetylmorphine;Morphine 6-acetate;O6 monoacetylmorphine;A-monoacetyl-morphinePW_C0225976AylMrf3559298829MorphineHMDB0014440Morphine is only found in individuals that have used or taken this drug. It is the principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [PubChem]The precise mechanism of the analgesic action of morphine is unknown. However, specific CNS opiate receptors have been identified and likely play a role in the expression of analgesic effects. Morphine first acts on the mu-opioid receptors. The mechanism of respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation.It has been shown that morphine binds to and inhibits GABA inhibitory interneurons. These interneurons normally inhibit the descending pain inhibition pathway. So, without the inhibitory signals, pain modulation can proceed downstream.57-27-2C015165288826173034450907DB00295[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2OC17H19NO3InChI=1S/C17H19NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2-5,10-11,13,16,19-20H,6-8H2,1H3/t10-,11+,13-,16-,17-/m0/s1BQJCRHHNABKAKU-KBQPJGBKSA-N(1S,5R,13R,14S,17R)-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10,15-tetraene-10,14-diol285.3377285.136493479-1.452morph01DBMET00313(-)-morphine;D-(-)-morphine;Morphine sulfate;Morphinum;Morphin;Morphina;(5alpha,6alpha)-17-methyl-7,8-didehydro-4,5-epoxymorphinan-3,6-diol;(5alpha,6alpha)-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol;(5r,6s,9r,13s,14r)-4,5-epoxy-n-methyl-7-morphinen-3,6-diol;(7r,7as,12bs)-3-methyl-2,3,4,4a,7,7a-hexahydro-1h-4,12-methano[1]benzofuro[3,2-e]isoquinoline-7,9-diol;Morfina;Morphia;Morphium;(5a,6a)-17-methyl-7,8-didehydro-4,5-epoxymorphinan-3,6-diol;(5α,6α)-17-methyl-7,8-didehydro-4,5-epoxymorphinan-3,6-diol;(5a,6a)-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol;(5α,6α)-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diolPW_C008829Morfin32371132417135602935623747201047213147221547323692662640513HeroinHMDB0061331Heroin, also known as diacetylmorphine or diagesil, belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic. Heroin is a drug which is used in the treatment of acute pain, myocardial infarction, acute pulmonary oedema, and chronic pain. Heroin exists as a solid and is considered to be practically insoluble (in water) and relatively neutral. Heroin can be biosynthesized from morphine. Heroin is a potentially toxic compound.561-27-3C065345462328278084575379DB01452[H][C@@]12OC3=C(OC(C)=O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2OC(C)=OC21H23NO5InChI=1S/C21H23NO5/c1-11(23)25-16-6-4-13-10-15-14-5-7-17(26-12(2)24)20-21(14,8-9-22(15)3)18(13)19(16)27-20/h4-7,14-15,17,20H,8-10H2,1-3H3/t14-,15+,17-,20-,21-/m0/s1GVGLGOZIDCSQPN-PVHGPHFFSA-N(1S,5R,13R,14S,17R)-14-(acetyloxy)-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10,15-tetraen-10-yl acetate369.411369.157622851-3.140(1S,5R,13R,14S,17R)-14-(acetyloxy)-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10,15-tetraen-10-yl acetate01(5alpha,6alpha)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol diacetate (ester);3,6-diacetylmorphine;7,8-dihydro-4,5-alpha-epoxy-17-methylmorphinan-3,6-alpha-diol diacetate;Diacetylmorphine;O,o'-diacetylmorphine;(5a,6a)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol diacetate (ester);(5a,6a)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol diacetic acid (ester);(5alpha,6alpha)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol diacetic acid (ester);(5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol diacetate (ester);(5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol diacetic acid (ester);7,8-dihydro-4,5-a-epoxy-17-methylmorphinan-3,6-a-diol diacetate;7,8-dihydro-4,5-a-epoxy-17-methylmorphinan-3,6-a-diol diacetic acid;7,8-dihydro-4,5-alpha-epoxy-17-methylmorphinan-3,6-alpha-diol diacetic acid;7,8-dihydro-4,5-α-epoxy-17-methylmorphinan-3,6-α-diol diacetate;7,8-dihydro-4,5-α-epoxy-17-methylmorphinan-3,6-α-diol diacetic acidPW_C040513Heroin3558293561374729369264261420WaterHMDB0002111Water is a chemical substance that is essential to all known forms of life. It appears colorless to the naked eye in small quantities, though it is actually slightly blue in color. It covers 71% of Earth's surface. Current estimates suggest that there are 1.4 billion cubic kilometers (330 million m3) of it available on Earth, and it exists in many forms. It appears mostly in the oceans (saltwater) and polar ice caps, but it is also present as clouds, rain water, rivers, freshwater aquifers, lakes, and sea ice. Water in these bodies perpetually moves through a cycle of evaporation, precipitation, and runoff to the sea. Clean water is essential to human life. In many parts of the world, it is in short supply. From a biological standpoint, water has many distinct properties that are critical for the proliferation of life that set it apart from other substances. It carries out this role by allowing organic compounds to react in ways that ultimately allow replication. All known forms of life depend on water. Water is vital both as a solvent in which many of the body's solutes dissolve and as an essential part of many metabolic processes within the body. Metabolism is the sum total of anabolism and catabolism. In anabolism, water is removed from molecules (through energy requiring enzymatic chemical reactions) in order to grow larger molecules (e.g. starches, triglycerides and proteins for storage of fuels and information). In catabolism, water is used to break bonds in order to generate smaller molecules (e.g. glucose, fatty acids and amino acids to be used for fuels for energy use or other purposes). Water is thus essential and central to these metabolic processes. Water is also central to photosynthesis and respiration. Photosynthetic cells use the sun's energy to split off water's hydrogen from oxygen. Hydrogen is combined with CO2 (absorbed from air or water) to form glucose and release oxygen. All living cells use such fuels and oxidize the hydrogen and carbon to capture the sun's energy and reform water and CO2 in the process (cellular respiration). Water is also central to acid-base neutrality and enzyme function. An acid, a hydrogen ion (H+, that is, a proton) donor, can be neutralized by a base, a proton acceptor such as hydroxide ion (OH-) to form water. Water is considered to be neutral, with a pH (the negative log of the hydrogen ion concentration) of 7. Acids have pH values less than 7 while bases have values greater than 7. Stomach acid (HCl) is useful to digestion. However, its corrosive effect on the esophagus during reflux can temporarily be neutralized by ingestion of a base such as aluminum hydroxide to produce the neutral molecules water and the salt aluminum chloride. Human biochemistry that involves enzymes usually performs optimally around a biologically neutral pH of 7.4. (Wikipedia).7732-18-5C0000196215377937OH2OInChI=1S/H2O/h1H2XLYOFNOQVPJJNP-UHFFFAOYSA-Nwater18.015318.0105646861water00FDB013390Dihydrogen oxide;Steam;[oh2];Acqua;Agua;Aqua;Bound water;Dihydridooxygen;Eau;H2o;Hoh;Hydrogen hydroxide;WasserPW_C001420H2O558949109513941513162144811352615624286521069120770338231883821094311377491465541590432018242532222678602727462778172805293143703164723634614598364727374941935030275156751959752141005227945236103529710553191115343113535511254021105470123548312554921265507127553413055371145541129559113556081185622108569165759140577810158411435853146587710758909559101475940151603215560591576087161612316361331596215162181666477178650718066001526713117684018868881607162205718120771932067211211722821372382147243215729519873502167388210740121274672227492224750019075881708201225823722684141629265261185027711922164120112811221328512250286122642871232724912520227126326512693290127052911271529213007298130193001302530113037302132612231332729415340308423273154269531843691322769142937701925377102132771311337721513477378331773973327747133377516115775363347762833677722337777593417781634377982347780713297823535278242353782703567911336080014368800393708059122880656119938303839479438411055739011063939111584439811987923211991512211996340612000840712004640812011312412036541212043040512043840912060641512079441412115842512124042912135112112138141912160743412211838212238443612275312012279737412280444312301244612306437612307213712313144712314213612316244812323145112338445012373046012381046412394045512416546912467039912493847112494547212530529712535347912538648112542448212548029912568248312570747812574548712605449012623849512627348412676448012689650112696350212701738812717720812719920912722750412750650712757651512783638912808239512817651329Acetic acidHMDB0000042Acetic acid is one of the simplest carboxylic acids. It is an important chemical reagent and industrial chemical that is used in the production of plastic soft drink bottles, photographic film; and polyvinyl acetate for wood glue, as well as many synthetic fibres and fabrics. In households diluted acetic acid is often used as a cleaning agent. In the food industry acetic acid is used as an acidity regulator. The acetyl group, derived from acetic acid, is fundamental to the biochemistry of virtually all forms of life. When bound to coenzyme A it is central to the metabolism of carbohydrates and fats. However, the concentration of free acetic acid in cells is kept at a low level to avoid disrupting the control of the pH of the cell contents. Acetic acid is produced and excreted by certain bacteria, notably the Acetobacter genus and Clostridium acetobutylicum. These bacteria are found universally in foodstuffs, water, and soil, and acetic acid is produced naturally as fruits and some other foods spoil. Acetic acid is also a component of the vaginal lubrication of humans and other primates, where it appears to serve as a mild antibacterial agent.64-19-7C0003317615366ACET171DB03166CC(O)=OC2H4O2InChI=1S/C2H4O2/c1-2(3)4/h1H3,(H,3,4)QTBSBXVTEAMEQO-UHFFFAOYSA-Nacetic acid60.05260.0211293720.731acetic acid0-1DBMET00484FDB008299Acetate;Ethanoate;Ethanoic acid;Ethylate;Ethylic acid;Glacial acetate;Glacial acetic acid;Kyselina octova;Methanecarboxylate;Methanecarboxylic acid;Vinegar;Vinegar acid;Acide acetique;Acoh;Ch3-cooh;Ch3co2h;E 260;E-260;E260;Essigsaeure;Ethoic acid;Hoac;Ins no. 260;Meco2h;Mecooh;EthoatePW_C000029Acoh568776478931428324728374730366158108622316669281609267261272329042702315494933769982947728911177823129778341321200591221206134141224561241228111351232384501250231181254372971266082991269752051281823882036Mu-type opioid receptorP35372Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphinHMDBP02643OPRM16q24-q25AY309009191038317873510374499CholinesteraseP06276Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
HMDBP00525BCHE3q26.1-q26.2M3238913.1.1.8333229356337449515479Liver carboxylesterase 1P23141Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate.
HMDBP00497CES116q22.2AY26810413.1.1.1; 3.1.1.5633332939893139972644476044778449318449615460136492910480Cocaine esteraseO00748Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine.
HMDBP00498CES216q22.1Y0961613.1.1.84; 3.1.1.1; 3.1.1.5633342939707739903139982644486044788449418449715473136493010254Mu-type opioid receptor1PW_P0002542732036815Cholinesterase1PW_P0008159394994816Liver carboxylesterase 11PW_P0008169404793817Cocaine esterase1PW_P00081794148011812falsePW_R001812Right6762405131Compoundfalse847314201Compoundtrue676388291Compoundfalse8474291Compoundtrue15518153.1.1.81810falsePW_R001810Right6758405131Compoundfalse847514201Compoundtrue6759225971Compoundfalse8476291Compoundtrue154781615488171811falsePW_R001811Right6760225971Compoundfalse847714201Compoundtrue676188291Compoundfalse8478291Compoundtrue1549816155081770712259729157false177575510regular20019070758829373true76589510regular100100102054051337157false39517010regular2001901020614203749false63512010regular787810207882937157false102517010regular2001901020829373false89511010regular100100102094051336157false177524510regular2001901021014203649false199544510regular78781021129363false200066010regular1001001021214203649false200096010regular787810213882936157false1775128510regular2001901021429363false2005118510regular100100316520367380false6804508subunitregular2001305601499372false7252308subunitregular1507056024793616false16955458subunitregular170905603480362false18855658subunitregular1507056044793616false169510708subunitregular170905605480362false188510858subunitregular1507027322543137331543165456781531337557256014568816313365573560245698173133655745603457081631336557556044571817313365576560510751M1125 360 C1120 453 793 374 785 475 149false18trueM 848.0644009829867 965.6115180941069 L 863 967 L 856.7346610946918 953.3711508775821false10752M11 12 C34 28 74 55 98 72 5true1816165M595 265 C625 265 695 265 725 265 5false1816166M674 198 C675 231 695 265 725 265 5false1816167M1025 265 C995 265 905 265 875 265 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false16168M945 210 C945 249 905 265 875 265 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false16169M1875 755 C1875 725 1876 465 1875 435 5false18trueM 1867.5 602.0096189432334 L 1875 615 L 1882.5 602.0096189432334false16170M2000 710 C1964 709 1874 671 1876 586 5false18trueM 1987.2357268644657 717.8786630414987 L 2000 710 L 1986.7947410904374 702.8851467245335false16171M1875 945 C1875 975 1646 843 1670 860 5true18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false16172M1995 484 C1967 484 1876 513 1876 586 5false18falsefalse16173M1875 945 C1875 975 1691 958 1715 975 5true1816174M2000 999 C1969 1001 1875 1043 1875 1118 5false1816175M1875 1285 C1875 1255 1875 986 1875 945 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false16176M2005 1235 C1976 1235 1875 1210 1875 1121 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false305631318123797291020516165Left97301020616166Left97311020716167Right97321020816168Right310315514567305731318103697331020916169Left97341021016170Left9735707116171Right97361021116172Right31041547456831051548456930583131811369737707116173Left97381021216174Left97391021316175Right97401021416176Right31061549457031071550457169963331314true0016regular665707510751Left389273210752Right4107223151401.01.002920014548279552200.60.602133427317746614301650.60.6023280360520M600 620 C600 570 650 520 700 520 C756 520 830 520 886 520 C936 520 986 570 986 620 C986 651 986 690 986 721 C986 771 936 821 886 821 C830 821 756 821 700 821 C650 821 600 771 600 721 C600 690 600 651 600 620 1true6386.0301.0683M1380 220 C1380 170 1430 120 1480 120 C1671 120 1920 120 2111 120 C2161 120 2211 170 2211 220 C2211 607 2211 1110 2211 1497 C2211 1547 2161 1597 2111 1597 C1920 1597 1671 1597 1480 1597 C1430 1597 1380 1547 1380 1497 C1380 1110 1380 607 1380 220 1true6831.01477.01942106013516412608703949098062422359210131866227816584049601592353156622516301902139153039#FFEEDE45091340