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<body>GABA (gamma-aminobutyric acid) is the major inhibitory neurotransmitter in the central nervous system.  It mediates its action through the ionotropic GABA-A and GABA-B receptors.  GABA-A receptors form ion channels, while GABA-B receptors are G-protein coupled receptors.  This pathway focuses on signaling pathway mediated by GABA-B receptor.
GABA-B receptor are located on both presynaptic and postsynaptic membrane.  Presynaptic GABA-B receptors are subdivided into autoreceptors that control GABA release, and heteroreceptors that inhibits all other neurotransmitter release.  Upon binding to GABA, the presynaptic GABA-B receptor decreases Ca ion influx by inhibiting voltage-dependent Ca channels, particularly N-type and P/Q type, via beta and gamma subunit of G protein, thus lowering the presynaptic Ca concentration and decreasing neurotransmitter release.  Postsynaptic GABA-B receptors induce a slow inhibitory postsynaptic current through the activation of an inward rectifying K channel (GIRK).  In addition, recent studies found that synaptic plasticity can be controlled by the cAMP pathway.
GABA-B receptors have been found to play a role in the field of substance abuse or addition.  It has been reported that administration of GABA-B agonist, such as baclofen, can reduce patients&apos; craving for cocaine or alcohol.  Recently, an association study showed close linkage between several SNPs of GABA B2 receptor and nicotine dependency.
Medline=11311380
Medline=16539894
OMIM=607340
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<celldesigner:protein id="pr3" name="G_beta_" type="GENERIC"/>
<celldesigner:protein id="pr4" name="G_gamma_" type="GENERIC"/>
<celldesigner:protein id="pr5" name="Ca channel" type="ION_CHANNEL"/>
<celldesigner:protein id="pr6" name="AC" type="GENERIC"/>
<celldesigner:protein id="pr7" name="PKA" type="GENERIC"/>
<celldesigner:protein id="p10" name="SNARE Complex" type="GENERIC">
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</celldesigner:protein>
<celldesigner:protein id="pr8" name="K channel" type="ION_CHANNEL"/>
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<celldesigner:listOfGenes/>
<celldesigner:listOfRNAs/>
<celldesigner:listOfAntisenseRNAs/>
<celldesigner:listOfLayers/>
<celldesigner:listOfBlockDiagrams/>
</celldesigner:extension>
</annotation>
<listOfUnitDefinitions>
<unitDefinition metaid="substance" id="substance" name="substance">
<listOfUnits>
<unit metaid="CDMT00044" kind="mole"/>
</listOfUnits>
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<listOfUnits>
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<unitDefinition metaid="length" id="length" name="length">
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<unit metaid="CDMT00047" kind="metre"/>
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</unitDefinition>
<unitDefinition metaid="time" id="time" name="time">
<listOfUnits>
<unit metaid="CDMT00048" kind="second"/>
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</unitDefinition>
</listOfUnitDefinitions>
<listOfCompartments>
<compartment metaid="default" id="default" size="1" units="volume"/>
<compartment metaid="c1" id="c1" name="Presynaptic" size="1" units="volume" outside="default">
<annotation>
<celldesigner:extension>
<celldesigner:name>Presynaptic</celldesigner:name>
</celldesigner:extension>
</annotation>
</compartment>
<compartment metaid="c2" id="c2" name="Postsynaptic" size="1" units="volume" outside="default">
<annotation>
<celldesigner:extension>
<celldesigner:name>Postsynaptic</celldesigner:name>
</celldesigner:extension>
</annotation>
</compartment>
<compartment metaid="c3" id="c3" name="Synaptic vesicle" size="1" units="volume" outside="c1">
<annotation>
<celldesigner:extension>
<celldesigner:name>Synaptic vesicle</celldesigner:name>
</celldesigner:extension>
</annotation>
</compartment>
</listOfCompartments>
<listOfSpecies>
<species metaid="s4" id="s4" name="GABA" compartment="default" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  GABA
Synonym:  Synonym not specified
Accession:  S05809
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
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<celldesigner:name>GABA</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s18" id="s18" name="GABA_minus_B receptor_slash__br_G protein_br_complex" compartment="c1" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  GABA-B receptor/ G protein complex
Synonym:  Synonym not specified
Accession:  U05887
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>COMPLEX</celldesigner:class>
<celldesigner:name>GABA_minus_B receptor_slash__br_G protein_br_complex</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s24" id="s24" name="G_sub_i_slash_o_endsub__alpha_" compartment="c1" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Gi/oalpha
Synonym:  Synonym not specified
Accession:  P05757
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>PROTEIN</celldesigner:class>
<celldesigner:proteinReference>pr2</celldesigner:proteinReference>
</celldesigner:speciesIdentity>
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<celldesigner:catalyzed reaction="re7"/>
</celldesigner:listOfCatalyzedReactions>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s27" id="s27" name="G_beta__gamma_ complex" compartment="c1" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Gbetagamma complex
Synonym:  Synonym not specified
Accession:  U05888
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>COMPLEX</celldesigner:class>
<celldesigner:name>G_beta__gamma_ complex</celldesigner:name>
</celldesigner:speciesIdentity>
<celldesigner:listOfCatalyzedReactions>
<celldesigner:catalyzed reaction="re5"/>
</celldesigner:listOfCatalyzedReactions>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s28" id="s28" name="GABA_minus_B_br_receptor_slash__br_GABA complex" compartment="c1" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  GABA-B receptor/ GABA complex
Synonym:  Synonym not specified
Accession:  U05889
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>COMPLEX</celldesigner:class>
<celldesigner:name>GABA_minus_B_br_receptor_slash__br_GABA complex</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s33" id="s33" name="GABA_minus_B_br_receptor_slash__br_GABA_slash__br_G protein complex" compartment="c1" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  GABA-B receptor/ GABA/ G protein complex
Synonym:  Synonym not specified
Accession:  U05890
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>COMPLEX</celldesigner:class>
<celldesigner:name>GABA_minus_B_br_receptor_slash__br_GABA_slash__br_G protein complex</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s39" id="s39" name="Ca channel" compartment="c1" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Voltage-dependent Ca channel
Synonym:  Synonym not specified
Accession:  P05753
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>PROTEIN</celldesigner:class>
<celldesigner:proteinReference>pr5</celldesigner:proteinReference>
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<celldesigner:catalyzed reaction="re6"/>
</celldesigner:listOfCatalyzedReactions>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s40" id="s40" name="Ca_super_2_plus_" compartment="default" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Ca2+
Synonym:  Synonym not specified
Accession:  U05899
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>ION</celldesigner:class>
<celldesigner:name>Ca_super_2_plus_</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s41" id="s41" name="Ca_super_2_plus_" compartment="c1" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Ca2+
Synonym:  Synonym not specified
Accession:  U05899
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>ION</celldesigner:class>
<celldesigner:name>Ca_super_2_plus_</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s42" id="s42" name="AC" compartment="c1" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Adenylate cyclase
Synonym:  adenylyl cyclase,adenyl cyclase
Accession:  P05760
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>PROTEIN</celldesigner:class>
<celldesigner:proteinReference>pr6</celldesigner:proteinReference>
</celldesigner:speciesIdentity>
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<celldesigner:catalyzed reaction="re8"/>
</celldesigner:listOfCatalyzedReactions>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s43" id="s43" name="PKA" compartment="c1" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  cAMP-dependent protein kinase
Synonym:  Synonym not specified
Accession:  P05752
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>PROTEIN</celldesigner:class>
<celldesigner:proteinReference>pr7</celldesigner:proteinReference>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s53" id="s53" name="Complex_br_(SNARE Complex/Ca_super_2+)" compartment="c3" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Long Name:  Long name not specified
Synonym:  Synonym not specified
Accession:  U05891
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>COMPLEX</celldesigner:class>
<celldesigner:name>Complex_br_(SNARE Complex/Ca_super_2+)</celldesigner:name>
</celldesigner:speciesIdentity>
<celldesigner:listOfCatalyzedReactions>
<celldesigner:catalyzed reaction="re18"/>
</celldesigner:listOfCatalyzedReactions>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s56" id="s56" name="SNARE Complex" compartment="c3" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  N-ethylmaleimide-sensitive factor attachment protein receptor
Synonym:  SNARE
Accession:  P05759
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>PROTEIN</celldesigner:class>
<celldesigner:proteinReference>p10</celldesigner:proteinReference>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s62" id="s62" name="Neurotransmitter" compartment="default" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Glutamate
Synonym:  Synonym not specified
Accession:  S05810
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>SIMPLE_MOLECULE</celldesigner:class>
<celldesigner:name>Neurotransmitter</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s64" id="s64" name="Neurotransmitter" compartment="c3" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Glutamate
Synonym:  Synonym not specified
Accession:  S05810
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>SIMPLE_MOLECULE</celldesigner:class>
<celldesigner:name>Neurotransmitter</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s65" id="s65" name="GABA_minus_B receptor_slash__br_G protein_br_complex" compartment="c2" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  GABA-B receptor/ G protein complex
Synonym:  Synonym not specified
Accession:  U05892
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>COMPLEX</celldesigner:class>
<celldesigner:name>GABA_minus_B receptor_slash__br_G protein_br_complex</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s70" id="s70" name="GABA_minus_B_br_receptor_slash__br_GABA_slash__br_G protein complex" compartment="c2" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  GABA-B receptor/ GABA/ G protein complex
Synonym:  Synonym not specified
Accession:  U05893
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>COMPLEX</celldesigner:class>
<celldesigner:name>GABA_minus_B_br_receptor_slash__br_GABA_slash__br_G protein complex</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s77" id="s77" name="GABA_minus_B_br_receptor_slash__br_GABA complex" compartment="c2" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  GABA-B receptor/ GABA complex
Synonym:  Synonym not specified
Accession:  U05894
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>COMPLEX</celldesigner:class>
<celldesigner:name>GABA_minus_B_br_receptor_slash__br_GABA complex</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s80" id="s80" name="G_beta__gamma_ complex" compartment="c2" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Gbetagamma complex
Synonym:  Synonym not specified
Accession:  U05895
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>COMPLEX</celldesigner:class>
<celldesigner:name>G_beta__gamma_ complex</celldesigner:name>
</celldesigner:speciesIdentity>
<celldesigner:listOfCatalyzedReactions>
<celldesigner:catalyzed reaction="re21"/>
</celldesigner:listOfCatalyzedReactions>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s83" id="s83" name="G_sub_i_slash_o_endsub__alpha_" compartment="c2" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Gi/oalpha
Synonym:  Synonym not specified
Accession:  P05757
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>PROTEIN</celldesigner:class>
<celldesigner:proteinReference>pr2</celldesigner:proteinReference>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s84" id="s84" name="K channel" compartment="c2" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Inwardly rectifying potassium channel Kir3.1
Synonym:  GIRK1,KCNJ3
Accession:  P05758
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>PROTEIN</celldesigner:class>
<celldesigner:proteinReference>pr8</celldesigner:proteinReference>
</celldesigner:speciesIdentity>
<celldesigner:listOfCatalyzedReactions>
<celldesigner:catalyzed reaction="re22"/>
</celldesigner:listOfCatalyzedReactions>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s86" id="s86" name="K_super__plus_" compartment="c2" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  K+
Synonym:  Synonym not specified
Accession:  U05898
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>ION</celldesigner:class>
<celldesigner:name>K_super__plus_</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s87" id="s87" name="K_super__plus_" compartment="default" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  K+
Synonym:  Synonym not specified
Accession:  U05898
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>ION</celldesigner:class>
<celldesigner:name>K_super__plus_</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s45" id="s45" name="neuronal function" compartment="c1" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Modulate neuronal function
Synonym:  Synonym not specified
Accession:  U05896
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>PHENOTYPE</celldesigner:class>
<celldesigner:name>neuronal function</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
<species metaid="s44" id="s44" name="Target ion channel" compartment="c1" initialAmount="0">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<body>Long Name:  Target ion channel modulation
Synonym:  Synonym not specified
Accession:  U05900
</body>
</html>
</notes>
<annotation>
<celldesigner:extension>
<celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment>
<celldesigner:speciesIdentity>
<celldesigner:class>PHENOTYPE</celldesigner:class>
<celldesigner:name>Target ion channel</celldesigner:name>
</celldesigner:speciesIdentity>
</celldesigner:extension>
</annotation>
</species>
</listOfSpecies>
<listOfReactions>
<reaction metaid="re3" id="re3" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>HETERODIMER_ASSOCIATION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s18" alias="csa2">
<celldesigner:linkAnchor position="SSE"/>
</celldesigner:baseReactant>
<celldesigner:baseReactant species="s4" alias="sa3">
<celldesigner:linkAnchor position="SSW"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s33" alias="csa1">
<celldesigner:linkAnchor position="E"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:connectScheme connectPolicy="direct">
<celldesigner:listOfLineDirection>
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<celldesigner:lineDirection arm="1" index="0" value="unknown"/>
<celldesigner:lineDirection arm="2" index="0" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:editPoints num0="0" num1="0" num2="0" tShapeIndex="0">0.6989097972055713,0.5229214093272895</celldesigner:editPoints>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00002" species="s18">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa2</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00003" species="s4">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa3</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00004" species="s33">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa1</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
</reaction>
<reaction metaid="re4" id="re4" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>DISSOCIATION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s33" alias="csa1">
<celldesigner:linkAnchor position="W"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s28" alias="csa4">
<celldesigner:linkAnchor position="NW"/>
</celldesigner:baseProduct>
<celldesigner:baseProduct species="s24" alias="sa12">
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</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:listOfProductLinks>
<celldesigner:productLink product="s27" alias="csa3" targetLineIndex="-1,1">
<celldesigner:linkAnchor position="N"/>
<celldesigner:line width="1.0" color="ff000000" type="Curve"/>
</celldesigner:productLink>
</celldesigner:listOfProductLinks>
<celldesigner:connectScheme connectPolicy="direct">
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<celldesigner:lineDirection arm="2" index="0" value="unknown"/>
<celldesigner:lineDirection arm="2" index="1" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
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<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00005" species="s33">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa1</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00006" species="s28">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa4</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00007" species="s24">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa12</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00008" species="s27">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa3</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
</reaction>
<reaction metaid="re5" id="re5" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>STATE_TRANSITION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s39" alias="sa20">
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</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s39" alias="sa21">
<celldesigner:linkAnchor position="E"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:connectScheme connectPolicy="direct" rectangleIndex="0">
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<celldesigner:line width="1.0" color="ff000000"/>
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<celldesigner:modification type="INHIBITION" modifiers="s27" aliases="csa3" targetLineIndex="-1,3">
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<celldesigner:linkTarget species="s27" alias="csa3">
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<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:modification>
</celldesigner:listOfModification>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00009" species="s39">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa20</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00010" species="s39">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa21</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
<listOfModifiers>
<modifierSpeciesReference metaid="CDMT00011" species="s27">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa3</celldesigner:alias>
</celldesigner:extension>
</annotation>
</modifierSpeciesReference>
</listOfModifiers>
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<reaction metaid="re6" id="re6" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>TRANSPORT</celldesigner:reactionType>
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<celldesigner:baseReactant species="s40" alias="sa22">
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</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s41" alias="sa23">
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<celldesigner:line width="1.0" color="ff000000"/>
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<celldesigner:line width="1.0" color="ff000000"/>
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<speciesReference metaid="CDMT00012" species="s40">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa22</celldesigner:alias>
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</annotation>
</speciesReference>
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<speciesReference metaid="CDMT00013" species="s41">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa23</celldesigner:alias>
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</speciesReference>
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<modifierSpeciesReference metaid="CDMT00014" species="s39">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa21</celldesigner:alias>
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<reaction metaid="re7" id="re7" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>STATE_TRANSITION</celldesigner:reactionType>
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<annotation>
<celldesigner:extension>
<celldesigner:alias>sa24</celldesigner:alias>
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<speciesReference metaid="CDMT00016" species="s42">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa25</celldesigner:alias>
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</annotation>
</speciesReference>
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<modifierSpeciesReference metaid="CDMT00017" species="s24">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa12</celldesigner:alias>
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<celldesigner:reactionType>STATE_TRANSITION</celldesigner:reactionType>
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<annotation>
<celldesigner:extension>
<celldesigner:alias>sa26</celldesigner:alias>
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<annotation>
<celldesigner:extension>
<celldesigner:alias>sa27</celldesigner:alias>
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<annotation>
<celldesigner:extension>
<celldesigner:alias>sa25</celldesigner:alias>
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<annotation>
<celldesigner:extension>
<celldesigner:reactionType>HETERODIMER_ASSOCIATION</celldesigner:reactionType>
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<celldesigner:baseProduct species="s53" alias="csa6">
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</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:connectScheme connectPolicy="direct">
<celldesigner:listOfLineDirection>
<celldesigner:lineDirection arm="0" index="0" value="unknown"/>
<celldesigner:lineDirection arm="1" index="0" value="unknown"/>
<celldesigner:lineDirection arm="2" index="0" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:editPoints num0="0" num1="0" num2="0" tShapeIndex="0">0.40871031935587254,0.4144290541121865</celldesigner:editPoints>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00021" species="s56">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa34</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00022" species="s41">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa23</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00023" species="s53">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa6</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
</reaction>
<reaction metaid="re18" id="re18" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>TRANSPORT</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s64" alias="sa46">
<celldesigner:linkAnchor position="S"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s62" alias="sa37">
<celldesigner:linkAnchor position="N"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:connectScheme connectPolicy="direct" rectangleIndex="0">
<celldesigner:listOfLineDirection>
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</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:line width="1.0" color="ff000000"/>
<celldesigner:listOfModification>
<celldesigner:modification type="TRIGGER" modifiers="s54" aliases="sa42" targetLineIndex="-1,2">
<celldesigner:connectScheme connectPolicy="direct">
<celldesigner:listOfLineDirection>
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</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:linkTarget species="s54" alias="sa42">
<celldesigner:linkAnchor position="NNE"/>
</celldesigner:linkTarget>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:modification>
</celldesigner:listOfModification>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00024" species="s64">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa46</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00025" species="s62">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa37</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
<listOfModifiers>
<modifierSpeciesReference metaid="CDMT00026" species="s53">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa6</celldesigner:alias>
</celldesigner:extension>
</annotation>
</modifierSpeciesReference>
</listOfModifiers>
</reaction>
<reaction metaid="re19" id="re19" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>HETERODIMER_ASSOCIATION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s65" alias="csa8">
<celldesigner:linkAnchor position="ENE"/>
</celldesigner:baseReactant>
<celldesigner:baseReactant species="s4" alias="sa47">
<celldesigner:linkAnchor position="SSE"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s70" alias="csa9">
<celldesigner:linkAnchor position="NW"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:connectScheme connectPolicy="direct">
<celldesigner:listOfLineDirection>
<celldesigner:lineDirection arm="0" index="0" value="unknown"/>
<celldesigner:lineDirection arm="1" index="0" value="unknown"/>
<celldesigner:lineDirection arm="2" index="0" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:editPoints num0="0" num1="0" num2="0" tShapeIndex="0">0.6929664117060206,0.24684070502161548</celldesigner:editPoints>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00027" species="s65">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa8</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00028" species="s4">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa47</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00029" species="s70">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa9</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
</reaction>
<reaction metaid="re20" id="re20" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>DISSOCIATION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s70" alias="csa9">
<celldesigner:linkAnchor position="SE"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s77" alias="csa10">
<celldesigner:linkAnchor position="SW"/>
</celldesigner:baseProduct>
<celldesigner:baseProduct species="s80" alias="csa11">
<celldesigner:linkAnchor position="NNW"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:listOfProductLinks>
<celldesigner:productLink product="s83" alias="sa61" targetLineIndex="-1,1">
<celldesigner:linkAnchor position="NE"/>
<celldesigner:line width="1.0" color="ff000000" type="Curve"/>
</celldesigner:productLink>
</celldesigner:listOfProductLinks>
<celldesigner:connectScheme connectPolicy="direct">
<celldesigner:listOfLineDirection>
<celldesigner:lineDirection arm="0" index="0" value="unknown"/>
<celldesigner:lineDirection arm="1" index="0" value="unknown"/>
<celldesigner:lineDirection arm="2" index="0" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:editPoints num0="0" num1="0" num2="0" tShapeIndex="0">0.1893210838816164,0.4767858370968119</celldesigner:editPoints>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00030" species="s70">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa9</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00031" species="s77">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa10</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00032" species="s80">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa11</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
<speciesReference metaid="CDMT00033" species="s83">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa61</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
</reaction>
<reaction metaid="re21" id="re21" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>STATE_TRANSITION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s84" alias="sa62">
<celldesigner:linkAnchor position="S"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s84" alias="sa63">
<celldesigner:linkAnchor position="N"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:connectScheme connectPolicy="direct" rectangleIndex="0">
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</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:line width="1.0" color="ff000000"/>
<celldesigner:listOfModification>
<celldesigner:modification type="MODULATION" modifiers="s80" aliases="csa11" targetLineIndex="-1,3">
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<celldesigner:lineDirection index="0" value="unknown"/>
</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:linkTarget species="s80" alias="csa11">
<celldesigner:linkAnchor position="E"/>
</celldesigner:linkTarget>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:modification>
</celldesigner:listOfModification>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00034" species="s84">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa62</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00035" species="s84">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa63</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
<listOfModifiers>
<modifierSpeciesReference metaid="CDMT00036" species="s80">
<annotation>
<celldesigner:extension>
<celldesigner:alias>csa11</celldesigner:alias>
</celldesigner:extension>
</annotation>
</modifierSpeciesReference>
</listOfModifiers>
</reaction>
<reaction metaid="re22" id="re22" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>TRANSPORT</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s86" alias="sa64">
<celldesigner:linkAnchor position="E"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s87" alias="sa65">
<celldesigner:linkAnchor position="W"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:connectScheme connectPolicy="direct" rectangleIndex="0">
<celldesigner:listOfLineDirection>
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</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:line width="1.0" color="ff000000"/>
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<celldesigner:modification type="TRIGGER" modifiers="s84" aliases="sa63" targetLineIndex="-1,2">
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<celldesigner:listOfLineDirection>
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</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:linkTarget species="s84" alias="sa63">
<celldesigner:linkAnchor position="N"/>
</celldesigner:linkTarget>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:modification>
</celldesigner:listOfModification>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00037" species="s86">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa64</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00038" species="s87">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa65</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
<listOfModifiers>
<modifierSpeciesReference metaid="CDMT00039" species="s84">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa63</celldesigner:alias>
</celldesigner:extension>
</annotation>
</modifierSpeciesReference>
</listOfModifiers>
</reaction>
<reaction metaid="re23" id="re23" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>MODULATION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s43" alias="sa27">
<celldesigner:linkAnchor position="NW"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s44" alias="sa28">
<celldesigner:linkAnchor position="E"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:connectScheme connectPolicy="direct">
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</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00040" species="s43">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa27</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00041" species="s44">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa28</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
</reaction>
<reaction metaid="re24" id="re24" reversible="false">
<annotation>
<celldesigner:extension>
<celldesigner:reactionType>MODULATION</celldesigner:reactionType>
<celldesigner:baseReactants>
<celldesigner:baseReactant species="s43" alias="sa27">
<celldesigner:linkAnchor position="W"/>
</celldesigner:baseReactant>
</celldesigner:baseReactants>
<celldesigner:baseProducts>
<celldesigner:baseProduct species="s45" alias="sa29">
<celldesigner:linkAnchor position="E"/>
</celldesigner:baseProduct>
</celldesigner:baseProducts>
<celldesigner:connectScheme connectPolicy="direct">
<celldesigner:listOfLineDirection>
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</celldesigner:listOfLineDirection>
</celldesigner:connectScheme>
<celldesigner:line width="1.0" color="ff000000"/>
</celldesigner:extension>
</annotation>
<listOfReactants>
<speciesReference metaid="CDMT00042" species="s43">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa27</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00043" species="s45">
<annotation>
<celldesigner:extension>
<celldesigner:alias>sa29</celldesigner:alias>
</celldesigner:extension>
</annotation>
</speciesReference>
</listOfProducts>
</reaction>
</listOfReactions>
</model>
</sbml>

