Table 1

Reaction equations, rate laws, and kinetic parameters comprising the platelet model

Reaction/quantityMechanismRate law/ruleParameter valuesReference*
SERCA shuttling SERCAE2 ⇆ SERCAE1 k1 · [SERCAE2] − k−1 · [SERCAE1] k1 = 600 s−1, k−1 = 600 s−1 1 
Ca2+cyt binding SERCA SERCAE1 + 2 Ca2+cyt ⇆ SERCAE1·Ca2+2 k1 · [SERCAE1] · [Ca2+cyt] · [Ca2+cyt] − k−1 · [SERCAE1·Ca2+2] k1 = 1 × 1015 M−2·s−1, k−1 = 10 s−1 1 
Phosphorylation of SERCA SERCAE1·Ca2+ ⇆ SERCAE1P·Ca2+ k1 · [SERCAE1Ca2+] − k-1 · [SERCAE1P·Ca2+] k1 = 700 s−1, k−1 = 5 s−1 1 
Ca2+ transport across IM SERCAE1P·Ca2+ ⇆ SERCAE2P·Ca2+ k1 · [SERCAE1P·Ca2+] − k-1 · [SERCAE2P·Ca2+] k1 = 600 s−1, k−1 = 50 s−1 1 
Ca2+dts release into DTS SERCAE2P·Ca2+2 ⇆ SERCAE2P + 2 Ca2+dts k1 · [SERCAE2P·Ca2+2] − k-1 · [SERCAE2P] · [Ca2+dts] · [Ca2+dts] k1 = 1000 s−1, k−1 = 4 × 109 M−2·s−1 1 
SERCA dephosphorylation SERCAE2P ⇆ SERCAE2 k1 · [SERCAE2P] − k-1 · [SERCAE2] k1 = 500 s−1, k−1 = 1 s−1 1 
IP3R inhibition IP3Rn + Ca2+cyt ⇆ IP3Ri1 [IP3Rn] · ((k1 · L1 + l2) · [Ca2+cyt] / (L1 + [Ca2+cyt] · (1 + L1 / L3))) − [IP3Ri1] · (k−1 + l−2) k1 = 0.64 s−1·μM−1, L1 = 0.12 μM, l2 = 1.7 s−1, L3 = 0.025 μM, k−1 = 0.04 s−1, l−2 = 0.8 s−1 2 
IP3R binding IP3 IP3Rn + IP3 ⇆ IP3Ro [IP3Rn] · [IP3] · ((k2 · L3 + l4 · [Ca2+cyt]) / (L3 + [Ca2+cyt] · (1 + L3 / L1))) − [IP3Ro] · ((k−2 + l-4 · [Ca2+cyt]) / (1 + [Ca2+cyt] / L5)) k2 = 37.4 s−1·μM−1, l4 = 1.7 s−1·μM−1, k−2 = 1.4 s−1, l-4 = 2.5 μM−1·s−1, L5 = 54.7 μM 2 
IP3R activation IP3Ro + Ca2+cyt ⇆ IP3Ra [IP3Ro] · ((k4 · L5 + l6) · [Ca2+cyt] / (L5 + [Ca2+cyt])) − [IP3Ra] · (L1 · (k-4 + l-6) / (L1 + [Ca2+cyt])) k4 = 4 s−1·μM−1, L5 = 54.7 μM, l6 = 4707 s−1, L1 = 0.12 μM, k-4 = 0.54 s−1·μM−1, l-6 = 11.4 s−1 2 
IP3R inhibition IP3Ra + Ca2+cyt ⇆ IP3Ri2 [IP3Ra] · (k1 · L1 + l2) · [Ca2+cyt] / (L1 + [Ca2+cyt]) − [IP3Ri2] · (k−1 + l−2) k1 = 0.64 s−1·μM−1, L1 = 0.12 μM, l2 = 1.7 s−1, k−1 = 0.04 s−1, l−2 = 0.8 s−1 2 
IP3R closing IP3Ro ⇆ IP3Rs [IP3Ro] · (k3 · L5 / (L5 + [Ca2+cyt])) − [IP3Rs] · k-3 k3 = 11 s−1·μM−1, L5 = 54.7 μM, k-3 = 29.8 s−1 2 
Channel open probability (Po)  (0.9 · IP3Ra / IP3Rtotal + 0.1 · pIP3Ro / IP3Rtotal)4  2 
IM potential (ψIM)  RT / zF · ln (Ca2+dts / Ca2+cyt)  † 
PM potential (ψPM)  RT / zF · ln (Ca2+prp / Ca2+cyt)  † 
Ca2+ release from DTS Ca2+dts ⇆ Ca2+cyt NIP3R · Po · γIP3R · e · ψIM γIP3R = 10 pS 3† 
Ca2+ leak across PM Ca2+prp ⇆ Ca2+cyt SAPM · γleak · ψPM γleak = 0.7 pS·m−2  
PLC-β* binding PI PLC-β* + PI ⇆ PLC-β*·PI k1 · [PLC-β*] · [PI] − k−1 · [PLC-β*·PI] k1 = 1 × 108 s−1·M−1, k−1 = 70499 s−1 4 
PLC-β* hydrolyzing PI PI → DAG + I1P kcat · [PLC-β*·PI] kcat = 1.43 s−1 4 
PLC-β* binding PIP PLC-β* + PIP ⇆ PLC-β*·PIP k1 · [PLC-β*] · [PIP] − k−1 · [PLC-β*·PIP] k1 = 1 × 108 s−1·M−1, k−1 = 19000 s−1 4 
PLC-β* hydrolyzing PIP PIP → DAG + IP2 kcat · [PLC-β*·PIP] kcat = 0.35 s−1 4 
PLC-β* binding PIP2 PLC-β* + PIP2 ⇆ PLC-β*·PIP2 k1 · [PLC-β*] · [PIP2] − k−1 · [PLC-β*·PIP2] k1 = 1 × 108 s−1·M−1, k−1 = 49990 s−1 4 
PLC-β* hydrolyzing PIP2 PIP2 → DAG + IP3 kcat · [PLC-β*·PIP2] kcat = 9.8505 s−1 4 
Phosphorylation of PI PI → PIP kcat · [PIK] · [PI] / (KM + [PI]) KM = 0.016 mM−1, kcat = 2.77 s−1 5 
Phosphorylation of PIP PIP → PIP2 kcat · [PIPK] · [PIP] / (KM + [PIP]) KM = 0.01 mM−1, kcat = 1.021 s−1 6 
Dephosphorylation of PIP2 PIP2 → PIP kcat · [PIP2P] · [PIP2] / (KM + [PIP2]) KM = 250 μM−1, kcat = 1 s−1 7 
Dephosphorylation of I1P I1P → I kcat · [IPP] · [I1P] / (KM + [I1P]) KM = 0.12 mM−1, kcat = 1 s−1 8 
Dephosphorylation of I4P I4P → I kcat · [IPP] · [I4P] / (KM + [I4P]) KM = 0.12 mM−1, kcat = 1 s−1 8 
Dephosphorylation of IP2 IP2 → I4P kcat · [IP2P] · [IP2] / (KM + [IP2]) KM = 0.9 μM−1, kcat = 0.05 s−1 9 
Dephosphorylation of IP3 IP3 → IP2 kcat · [IP3P] · [IP3] / (KM + [IP3]) KM = 24 μM−1, kcat = 31 s−1 10 
Phosphorylation of DAG DAG → PA kcat · [DGK] · [DAG] / (KM + [DAG]) KM = 0.25 mM−1, kcat = 0.26 s−1 11 
Synthesis of CDPDG CTP + PA → CDPDG kcat · [CDS] · [PA] · [CTP] / (KM1 · KM2 + (KM1 · [PA] + KM2 · [CTP] + [PA] · [CTP])) KM1 = 0.5 mM−1, KM2 = 1.0 mM−1, kcat = 8.9 s−1 12 
Synthesis of PI CDPDG + I → PI kcat · [PIS] · [CDPDG] · [I] / (KM1 · KM2 + (KM1 · [I] + KM2 · [CDPDG] + [I] · [CDPDG])) KM1 = 13 μM−1, KM2 = 0.28 mM−1, kcat = 13.6 s−1 13 
Activation of PKC PKC ⇆ PKCa k1 · [PKC] − k−1 · [PKCa] k1 = 1 s−1, k−1 = 2 s−1 14 
Activation of PKC·Ca2+cyt PKC·Ca2+cyt ⇆ PKCa·Ca2+cyt k1 · [PKC·Ca2+cyt] − k−1 · [PKCa·Ca2+cyt] k1 = 1.3 s−1, k−1 = 3.5 s−1 14 
Activation of PKC·Ca2+cyt ·DG PKC·Ca2+cyt ·DAG ⇆ PKCa·Ca2+cyt ·DAG k1 · [PKC·Ca2+cyt ·DAG] − k−1 · [PKCa·Ca2+cyt ·DAG] k1 = 1 s−1, k−1 = 0.1 s−1 14 
PKC binding Ca2+cyt PKC + Ca2+cyt ⇆ PKC·Ca2+cyt kon · [PKC] · [Ca2+cyt] − koff · [PKC·Ca2+cyt] kon = 0.6 × 106 M−1·s−1, koff = 0.5 s−1 14 
PKC·Ca2+cyt binding DAG PKC·Ca2+cyt + DAG ⇆ PKC·Ca2+cyt ·DAG kon · [PKC·Ca2+cyt] · [DAG] − koff · [PKC·Ca2+cyt ·DAG] kon = 8 × 103 M−1·s−1, koff = 8.6348 s−1 14 
PKCa binding Ca2+cyt PKCa + Ca2+cyt ⇆ PKCa·Ca2+cyt kon · [PKCa] · [Ca2+cyt] − koff · [PKCa·Ca2+cyt] kon = 0.6 × 106 M−1·s−1, koff = 0.5 s−1 14 
PKCa·Ca2+cyt binding DAG PKCa·Ca2+cyt + DAG ⇆ PKCa·Ca2+cyt ·DAG kon · [PKCa·Ca2+cyt] · [DAG] − koff · [PKCa·Ca2+cyt ·DAG] kon = 8 × 103 M−1·s−1, koff = 8.6348 s−1 14 
Activation of P2Y1 P2Y1 ⇆ P2Y1* k1 · [P2Y1] − (k1 / Kact) · [P2Y1*] k1 = 7.9 s−1, Kact = 0.0001 15, 16† 
Activation of P2Y1·ADP P2Y1·ADP ⇆ P2Y1*·ADP αk1 · [P2Y1·ADP] − (k1 / Kact) · [P2Y1*·ADP] α = 3.35, k1 = 7.9 s−1, Kact = 0.0001 15, 16† 
Activation of P2Y1·Gq·GDP P2Y1·Gq·GDP ⇆ P2Y1*·Gq·GDP βk1 · [P2Y1·Gq·GDP] − (k1 / Kact) · [P2Y1*·Gq·GDP] β = 6.62, k1 = 7.9 s−1, Kact = 0.0001 15, 16† 
Activation of P2Y1·ADP·Gq·GDP P2Y1·ADP·Gq·GDP ⇆ P2Y1*·ADP·Gq·GDP αβδk1 · [P2Y1·ADP·Gq·GDP] − (k1 / Kact) · [P2Y1*·ADP·Gq·GDP] α = 3.35, β = 6.62, δ = 9.85, k1 = 7.9 s−1, Kact = 0.0001 15, 16† 
P2Y1* binding Gq·GDP P2Y1* + Gq·GDP ⇆ P2Y1*·Gq·GDP βk11 · [P2Y1*] · [Gq·GDP] − (k11 / Kg) · [P2Y1*·Gq·GDP] β = 6.62, k11 = 0.59 μM−1·s−1, Kq = 0.032 μM−1 15, 16† 
P2Y1*·ADP binding Gq·GDP P2Y1*·ADP + Gq·GDP ⇆ P2Y1*·ADP·Gq·GDP βk11 · [P2Y1*·ADP] · [Gq·GDP] − (k11 / (δγKg)) · [P2Y1*·Gq·GDP] β = 6.62, k11 = 0.59 μM−1·s−1, δ = 9.85, γ = 9.39, Kq = 0.032 μM−1 15, 16† 
P2Y1 binding ADP P2Y1 + ADP ⇆ P2Y1·ADP k3 · [P2Y1] · [ADP] − (Kdk3) · [P2Y1·ADP] k3 = 9.6 × 107 M−1·s−1, Kd = 99 nM 15, 16† 
P2Y1·Gq·GDP binding ADP P2Y1·Gq·GDP + ADP ⇆ P2Y1·ADP·Gq·GDP k3 · [P2Y1·Gq·GDP] · [ADP] - (Kdk3 / γ) · [P2Y1·ADP·Gq·GDP] k3 = 9.6 × 107 M−1·s−1, Kd = 99 nM, γ = 9.39 15, 16† 
P2Y1* binding ADP P2Y1* + ADP ⇆ P2Y1*·ADP αk3 · [P2Y1*] · [ADP] − Kdk3 · [P2Y1*·ADP] α = 3.35, k3 = 9.6 × 107 M−1·s−1, Kd = 99 nM 15, 16† 
P2Y1*·Gq·GDP binding ADP P2Y1*·Gq·GDP + ADP ⇆ P2Y1*·ADP·Gq·GDP αk3 · [P2Y1*·Gq·GDP] · [ADP] − (Kdk3 / δγ) · [P2Y1*·ADP·Gq·GDP] α = 3.35, k3 = 9.6 × 107 M−1·s−1, Kd = 99 nM, δ = 9.85, γ = 9.39 15, 16† 
P2Y1*·Gq·GDP releasing GDP P2Y1*·Gq·GDP ⇆ P2Y1*·Gq k1 · [P2Y1*·Gq·GDP] − k−1 · [P2Y1*·Gq] · [GDP] k1 = 17.8 s−1, k−1 = 1 × 106 M−1·s−1 15, 16† 
P2Y1*·Gq binding GTP P2Y1*·Gq ⇆ P2Y1*·Gq·GTP k1 · [P2Y1*·Gq] · [GTP] − k−1 · [P2Y1*·Gq·GTP] k1 = 1 × 105 M−1·s−1, k−1 = 8 s−1 15, 16† 
P2Y1*·ADP·Gq·GDP releasing GDP P2Y1*·ADP·Gq·GDP ⇆ P2Y1*·ADP·Gq k1 · [P2Y1*·ADP·Gq·GDP] − k−1 · [P2Y1*·ADP·Gq] · [GDP] k1 = 17.8 s−1, k−1 = 1 × 106 M−1·s−1 15, 16† 
P2Y1*·ADP·Gq binding GTP P2Y1*·ADP·Gq ⇆ P2Y1*·ADP·Gq·GTP k1 · [P2Y1*·ADP·Gq] · [GTP] − k−1 · [P2Y1*·ADP·Gq·GTP] k1 = 1 × 105 M−1·s−1, k−1 = 8 s−1 15, 16† 
P2Y1*·Gq·GTP releasing Gq·GTP P2Y1*·Gq·GTP ⇆ P2Y1* + Gq·GTP k1 · [P2Y1*·Gq·GTP] − k−1 · [P2Y1*] · [Gq·GTP] k1 = 850 s−1, k−1 = 1 × 107 M−1·s−1 15, 16† 
P2Y1*·ADP·Gq·GTP releasing Gq·GTP P2Y1*·ADP·Gq·GTP ⇆ P2Y1*·ADP + Gq·GTP k1 · [P2Y1*·ADP·Gq·GTP] − k−1 · [P2Y1*·ADP] · [Gq·GTP] k1 = 850 s−1, k−1 = 1 × 107 M−1·s−1 15, 16† 
Gq·GTP autohydrolysis Gq·GTP ⇆ Gα·GDP + Gβγ kGTP · [Gq·GTP] kGTP = 0.013 s−1 17 
Activated Gq subunit association Gα·GTP + Gβγ ⇆ Gq·GTP k1 · [Gα·GTP] · [Gβγ] − k−1 · [Gq·GTP] k1 = 0.10 μM−1·s−1, k−1 = 7.78 s−1 15 
Unactivated Gq subunit association Gα·GDP + Gβγ ⇆ Gq·GDP k1 · [Gα·GDP] · [Gβγ] − k−1 · [Gq·GDP] k1 = 0.10 μM−1·s−1, k−1 = 7.78 s−1 15 
PLC-β binding Gq·GTP PLC-β + Gq·GTP ⇆ PLC-β*·Gq·GTP k1 · [PLC-β] · [Gq·GTP] − k−1 · [PLC-β*·Gq·GTP] k1 = 1.61 μM−1·s−1, k−1 = 0.19 s−1 15, 16† 
PLC-β* hydrolyzing Gq·GTP PLC-β*·Gq·GTP → PLC-β·Gq·GDP kcat · [PLC-β*·Gq·GTP] kcat = 25 s−1 17 
PLC-β releasing Gq·GDP PLC-β·Gq·GDP ⇆ PLC-β + Gq·GDP k1 · [PLC·Gq·GDP] − k−1 · [PLC-β] · [Gq·GDP] k1 = 1 × 105 s−1, k−1 = 100 M−1·s−1 15, 16† 
Reaction/quantityMechanismRate law/ruleParameter valuesReference*
SERCA shuttling SERCAE2 ⇆ SERCAE1 k1 · [SERCAE2] − k−1 · [SERCAE1] k1 = 600 s−1, k−1 = 600 s−1 1 
Ca2+cyt binding SERCA SERCAE1 + 2 Ca2+cyt ⇆ SERCAE1·Ca2+2 k1 · [SERCAE1] · [Ca2+cyt] · [Ca2+cyt] − k−1 · [SERCAE1·Ca2+2] k1 = 1 × 1015 M−2·s−1, k−1 = 10 s−1 1 
Phosphorylation of SERCA SERCAE1·Ca2+ ⇆ SERCAE1P·Ca2+ k1 · [SERCAE1Ca2+] − k-1 · [SERCAE1P·Ca2+] k1 = 700 s−1, k−1 = 5 s−1 1 
Ca2+ transport across IM SERCAE1P·Ca2+ ⇆ SERCAE2P·Ca2+ k1 · [SERCAE1P·Ca2+] − k-1 · [SERCAE2P·Ca2+] k1 = 600 s−1, k−1 = 50 s−1 1 
Ca2+dts release into DTS SERCAE2P·Ca2+2 ⇆ SERCAE2P + 2 Ca2+dts k1 · [SERCAE2P·Ca2+2] − k-1 · [SERCAE2P] · [Ca2+dts] · [Ca2+dts] k1 = 1000 s−1, k−1 = 4 × 109 M−2·s−1 1 
SERCA dephosphorylation SERCAE2P ⇆ SERCAE2 k1 · [SERCAE2P] − k-1 · [SERCAE2] k1 = 500 s−1, k−1 = 1 s−1 1 
IP3R inhibition IP3Rn + Ca2+cyt ⇆ IP3Ri1 [IP3Rn] · ((k1 · L1 + l2) · [Ca2+cyt] / (L1 + [Ca2+cyt] · (1 + L1 / L3))) − [IP3Ri1] · (k−1 + l−2) k1 = 0.64 s−1·μM−1, L1 = 0.12 μM, l2 = 1.7 s−1, L3 = 0.025 μM, k−1 = 0.04 s−1, l−2 = 0.8 s−1 2 
IP3R binding IP3 IP3Rn + IP3 ⇆ IP3Ro [IP3Rn] · [IP3] · ((k2 · L3 + l4 · [Ca2+cyt]) / (L3 + [Ca2+cyt] · (1 + L3 / L1))) − [IP3Ro] · ((k−2 + l-4 · [Ca2+cyt]) / (1 + [Ca2+cyt] / L5)) k2 = 37.4 s−1·μM−1, l4 = 1.7 s−1·μM−1, k−2 = 1.4 s−1, l-4 = 2.5 μM−1·s−1, L5 = 54.7 μM 2 
IP3R activation IP3Ro + Ca2+cyt ⇆ IP3Ra [IP3Ro] · ((k4 · L5 + l6) · [Ca2+cyt] / (L5 + [Ca2+cyt])) − [IP3Ra] · (L1 · (k-4 + l-6) / (L1 + [Ca2+cyt])) k4 = 4 s−1·μM−1, L5 = 54.7 μM, l6 = 4707 s−1, L1 = 0.12 μM, k-4 = 0.54 s−1·μM−1, l-6 = 11.4 s−1 2 
IP3R inhibition IP3Ra + Ca2+cyt ⇆ IP3Ri2 [IP3Ra] · (k1 · L1 + l2) · [Ca2+cyt] / (L1 + [Ca2+cyt]) − [IP3Ri2] · (k−1 + l−2) k1 = 0.64 s−1·μM−1, L1 = 0.12 μM, l2 = 1.7 s−1, k−1 = 0.04 s−1, l−2 = 0.8 s−1 2 
IP3R closing IP3Ro ⇆ IP3Rs [IP3Ro] · (k3 · L5 / (L5 + [Ca2+cyt])) − [IP3Rs] · k-3 k3 = 11 s−1·μM−1, L5 = 54.7 μM, k-3 = 29.8 s−1 2 
Channel open probability (Po)  (0.9 · IP3Ra / IP3Rtotal + 0.1 · pIP3Ro / IP3Rtotal)4  2 
IM potential (ψIM)  RT / zF · ln (Ca2+dts / Ca2+cyt)  † 
PM potential (ψPM)  RT / zF · ln (Ca2+prp / Ca2+cyt)  † 
Ca2+ release from DTS Ca2+dts ⇆ Ca2+cyt NIP3R · Po · γIP3R · e · ψIM γIP3R = 10 pS 3† 
Ca2+ leak across PM Ca2+prp ⇆ Ca2+cyt SAPM · γleak · ψPM γleak = 0.7 pS·m−2  
PLC-β* binding PI PLC-β* + PI ⇆ PLC-β*·PI k1 · [PLC-β*] · [PI] − k−1 · [PLC-β*·PI] k1 = 1 × 108 s−1·M−1, k−1 = 70499 s−1 4 
PLC-β* hydrolyzing PI PI → DAG + I1P kcat · [PLC-β*·PI] kcat = 1.43 s−1 4 
PLC-β* binding PIP PLC-β* + PIP ⇆ PLC-β*·PIP k1 · [PLC-β*] · [PIP] − k−1 · [PLC-β*·PIP] k1 = 1 × 108 s−1·M−1, k−1 = 19000 s−1 4 
PLC-β* hydrolyzing PIP PIP → DAG + IP2 kcat · [PLC-β*·PIP] kcat = 0.35 s−1 4 
PLC-β* binding PIP2 PLC-β* + PIP2 ⇆ PLC-β*·PIP2 k1 · [PLC-β*] · [PIP2] − k−1 · [PLC-β*·PIP2] k1 = 1 × 108 s−1·M−1, k−1 = 49990 s−1 4 
PLC-β* hydrolyzing PIP2 PIP2 → DAG + IP3 kcat · [PLC-β*·PIP2] kcat = 9.8505 s−1 4 
Phosphorylation of PI PI → PIP kcat · [PIK] · [PI] / (KM + [PI]) KM = 0.016 mM−1, kcat = 2.77 s−1 5 
Phosphorylation of PIP PIP → PIP2 kcat · [PIPK] · [PIP] / (KM + [PIP]) KM = 0.01 mM−1, kcat = 1.021 s−1 6 
Dephosphorylation of PIP2 PIP2 → PIP kcat · [PIP2P] · [PIP2] / (KM + [PIP2]) KM = 250 μM−1, kcat = 1 s−1 7 
Dephosphorylation of I1P I1P → I kcat · [IPP] · [I1P] / (KM + [I1P]) KM = 0.12 mM−1, kcat = 1 s−1 8 
Dephosphorylation of I4P I4P → I kcat · [IPP] · [I4P] / (KM + [I4P]) KM = 0.12 mM−1, kcat = 1 s−1 8 
Dephosphorylation of IP2 IP2 → I4P kcat · [IP2P] · [IP2] / (KM + [IP2]) KM = 0.9 μM−1, kcat = 0.05 s−1 9 
Dephosphorylation of IP3 IP3 → IP2 kcat · [IP3P] · [IP3] / (KM + [IP3]) KM = 24 μM−1, kcat = 31 s−1 10 
Phosphorylation of DAG DAG → PA kcat · [DGK] · [DAG] / (KM + [DAG]) KM = 0.25 mM−1, kcat = 0.26 s−1 11 
Synthesis of CDPDG CTP + PA → CDPDG kcat · [CDS] · [PA] · [CTP] / (KM1 · KM2 + (KM1 · [PA] + KM2 · [CTP] + [PA] · [CTP])) KM1 = 0.5 mM−1, KM2 = 1.0 mM−1, kcat = 8.9 s−1 12 
Synthesis of PI CDPDG + I → PI kcat · [PIS] · [CDPDG] · [I] / (KM1 · KM2 + (KM1 · [I] + KM2 · [CDPDG] + [I] · [CDPDG])) KM1 = 13 μM−1, KM2 = 0.28 mM−1, kcat = 13.6 s−1 13 
Activation of PKC PKC ⇆ PKCa k1 · [PKC] − k−1 · [PKCa] k1 = 1 s−1, k−1 = 2 s−1 14 
Activation of PKC·Ca2+cyt PKC·Ca2+cyt ⇆ PKCa·Ca2+cyt k1 · [PKC·Ca2+cyt] − k−1 · [PKCa·Ca2+cyt] k1 = 1.3 s−1, k−1 = 3.5 s−1 14 
Activation of PKC·Ca2+cyt ·DG PKC·Ca2+cyt ·DAG ⇆ PKCa·Ca2+cyt ·DAG k1 · [PKC·Ca2+cyt ·DAG] − k−1 · [PKCa·Ca2+cyt ·DAG] k1 = 1 s−1, k−1 = 0.1 s−1 14 
PKC binding Ca2+cyt PKC + Ca2+cyt ⇆ PKC·Ca2+cyt kon · [PKC] · [Ca2+cyt] − koff · [PKC·Ca2+cyt] kon = 0.6 × 106 M−1·s−1, koff = 0.5 s−1 14 
PKC·Ca2+cyt binding DAG PKC·Ca2+cyt + DAG ⇆ PKC·Ca2+cyt ·DAG kon · [PKC·Ca2+cyt] · [DAG] − koff · [PKC·Ca2+cyt ·DAG] kon = 8 × 103 M−1·s−1, koff = 8.6348 s−1 14 
PKCa binding Ca2+cyt PKCa + Ca2+cyt ⇆ PKCa·Ca2+cyt kon · [PKCa] · [Ca2+cyt] − koff · [PKCa·Ca2+cyt] kon = 0.6 × 106 M−1·s−1, koff = 0.5 s−1 14 
PKCa·Ca2+cyt binding DAG PKCa·Ca2+cyt + DAG ⇆ PKCa·Ca2+cyt ·DAG kon · [PKCa·Ca2+cyt] · [DAG] − koff · [PKCa·Ca2+cyt ·DAG] kon = 8 × 103 M−1·s−1, koff = 8.6348 s−1 14 
Activation of P2Y1 P2Y1 ⇆ P2Y1* k1 · [P2Y1] − (k1 / Kact) · [P2Y1*] k1 = 7.9 s−1, Kact = 0.0001 15, 16† 
Activation of P2Y1·ADP P2Y1·ADP ⇆ P2Y1*·ADP αk1 · [P2Y1·ADP] − (k1 / Kact) · [P2Y1*·ADP] α = 3.35, k1 = 7.9 s−1, Kact = 0.0001 15, 16† 
Activation of P2Y1·Gq·GDP P2Y1·Gq·GDP ⇆ P2Y1*·Gq·GDP βk1 · [P2Y1·Gq·GDP] − (k1 / Kact) · [P2Y1*·Gq·GDP] β = 6.62, k1 = 7.9 s−1, Kact = 0.0001 15, 16† 
Activation of P2Y1·ADP·Gq·GDP P2Y1·ADP·Gq·GDP ⇆ P2Y1*·ADP·Gq·GDP αβδk1 · [P2Y1·ADP·Gq·GDP] − (k1 / Kact) · [P2Y1*·ADP·Gq·GDP] α = 3.35, β = 6.62, δ = 9.85, k1 = 7.9 s−1, Kact = 0.0001 15, 16† 
P2Y1* binding Gq·GDP P2Y1* + Gq·GDP ⇆ P2Y1*·Gq·GDP βk11 · [P2Y1*] · [Gq·GDP] − (k11 / Kg) · [P2Y1*·Gq·GDP] β = 6.62, k11 = 0.59 μM−1·s−1, Kq = 0.032 μM−1 15, 16† 
P2Y1*·ADP binding Gq·GDP P2Y1*·ADP + Gq·GDP ⇆ P2Y1*·ADP·Gq·GDP βk11 · [P2Y1*·ADP] · [Gq·GDP] − (k11 / (δγKg)) · [P2Y1*·Gq·GDP] β = 6.62, k11 = 0.59 μM−1·s−1, δ = 9.85, γ = 9.39, Kq = 0.032 μM−1 15, 16† 
P2Y1 binding ADP P2Y1 + ADP ⇆ P2Y1·ADP k3 · [P2Y1] · [ADP] − (Kdk3) · [P2Y1·ADP] k3 = 9.6 × 107 M−1·s−1, Kd = 99 nM 15, 16† 
P2Y1·Gq·GDP binding ADP P2Y1·Gq·GDP + ADP ⇆ P2Y1·ADP·Gq·GDP k3 · [P2Y1·Gq·GDP] · [ADP] - (Kdk3 / γ) · [P2Y1·ADP·Gq·GDP] k3 = 9.6 × 107 M−1·s−1, Kd = 99 nM, γ = 9.39 15, 16† 
P2Y1* binding ADP P2Y1* + ADP ⇆ P2Y1*·ADP αk3 · [P2Y1*] · [ADP] − Kdk3 · [P2Y1*·ADP] α = 3.35, k3 = 9.6 × 107 M−1·s−1, Kd = 99 nM 15, 16† 
P2Y1*·Gq·GDP binding ADP P2Y1*·Gq·GDP + ADP ⇆ P2Y1*·ADP·Gq·GDP αk3 · [P2Y1*·Gq·GDP] · [ADP] − (Kdk3 / δγ) · [P2Y1*·ADP·Gq·GDP] α = 3.35, k3 = 9.6 × 107 M−1·s−1, Kd = 99 nM, δ = 9.85, γ = 9.39 15, 16† 
P2Y1*·Gq·GDP releasing GDP P2Y1*·Gq·GDP ⇆ P2Y1*·Gq k1 · [P2Y1*·Gq·GDP] − k−1 · [P2Y1*·Gq] · [GDP] k1 = 17.8 s−1, k−1 = 1 × 106 M−1·s−1 15, 16† 
P2Y1*·Gq binding GTP P2Y1*·Gq ⇆ P2Y1*·Gq·GTP k1 · [P2Y1*·Gq] · [GTP] − k−1 · [P2Y1*·Gq·GTP] k1 = 1 × 105 M−1·s−1, k−1 = 8 s−1 15, 16† 
P2Y1*·ADP·Gq·GDP releasing GDP P2Y1*·ADP·Gq·GDP ⇆ P2Y1*·ADP·Gq k1 · [P2Y1*·ADP·Gq·GDP] − k−1 · [P2Y1*·ADP·Gq] · [GDP] k1 = 17.8 s−1, k−1 = 1 × 106 M−1·s−1 15, 16† 
P2Y1*·ADP·Gq binding GTP P2Y1*·ADP·Gq ⇆ P2Y1*·ADP·Gq·GTP k1 · [P2Y1*·ADP·Gq] · [GTP] − k−1 · [P2Y1*·ADP·Gq·GTP] k1 = 1 × 105 M−1·s−1, k−1 = 8 s−1 15, 16† 
P2Y1*·Gq·GTP releasing Gq·GTP P2Y1*·Gq·GTP ⇆ P2Y1* + Gq·GTP k1 · [P2Y1*·Gq·GTP] − k−1 · [P2Y1*] · [Gq·GTP] k1 = 850 s−1, k−1 = 1 × 107 M−1·s−1 15, 16† 
P2Y1*·ADP·Gq·GTP releasing Gq·GTP P2Y1*·ADP·Gq·GTP ⇆ P2Y1*·ADP + Gq·GTP k1 · [P2Y1*·ADP·Gq·GTP] − k−1 · [P2Y1*·ADP] · [Gq·GTP] k1 = 850 s−1, k−1 = 1 × 107 M−1·s−1 15, 16† 
Gq·GTP autohydrolysis Gq·GTP ⇆ Gα·GDP + Gβγ kGTP · [Gq·GTP] kGTP = 0.013 s−1 17 
Activated Gq subunit association Gα·GTP + Gβγ ⇆ Gq·GTP k1 · [Gα·GTP] · [Gβγ] − k−1 · [Gq·GTP] k1 = 0.10 μM−1·s−1, k−1 = 7.78 s−1 15 
Unactivated Gq subunit association Gα·GDP + Gβγ ⇆ Gq·GDP k1 · [Gα·GDP] · [Gβγ] − k−1 · [Gq·GDP] k1 = 0.10 μM−1·s−1, k−1 = 7.78 s−1 15 
PLC-β binding Gq·GTP PLC-β + Gq·GTP ⇆ PLC-β*·Gq·GTP k1 · [PLC-β] · [Gq·GTP] − k−1 · [PLC-β*·Gq·GTP] k1 = 1.61 μM−1·s−1, k−1 = 0.19 s−1 15, 16† 
PLC-β* hydrolyzing Gq·GTP PLC-β*·Gq·GTP → PLC-β·Gq·GDP kcat · [PLC-β*·Gq·GTP] kcat = 25 s−1 17 
PLC-β releasing Gq·GDP PLC-β·Gq·GDP ⇆ PLC-β + Gq·GDP k1 · [PLC·Gq·GDP] − k−1 · [PLC-β] · [Gq·GDP] k1 = 1 × 105 s−1, k−1 = 100 M−1·s−1 15, 16† 
*

Of the 132 kinetic parameters, all but 11 were obtained from human platelet data or data from platelet-specific enzyme isoforms. These 11 parameters correspond to references 6, 8, 9, 11, and 12.

1.

Dode L, Vilsen B, Van Baelen K, Wuytack F, Clausen JD, Andersen JP. Dissection of the functional differences between sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 1 and 3 isoforms by steady-state and transient kinetic analyses. J Biol Chem. 2002;277:45579-45591.

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Sneyd J, Dufour JF. A dynamic model of the type-2 inositol trisphosphate receptor. Proc Natl Acad Sci U S A. 2002;99:2398-2403.

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Zschauer A, van Breemen C, Buhler FR, Nelson MT. Calcium channels in thrombin-activated human platelet membrane. Nature. 1988;334:703-705.

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Rittenhouse SE. Human platelets contain phospholipase C that hydrolyzes polyphosphoinositides. Proc Natl Acad Sci U S A. 1983;80:5417-5420.

5.

Kanoh H, Banno Y, Hirata M, Nozawa Y. Partial purification and characterization of phosphatidylinositol kinases from human platelets .Biochim Biophys Acta. 1990;1046:120-126.

6.

Urumow T, Wieland OH. Purification and partial characterization of phosphatidylinositol-4-phosphate kinase from rat liver plasma membranes: further evidence for a stimulatory G-protein. Biochim Biophys Acta. 1990;1052:152-158.

7.

Matzaris M, Jackson SP, Laxminarayan KM, Speed CJ, Mitchell CA. Identification and characterization of the phosphatidylinositol-(4, 5)-bisphosphate 5-phosphatase in human platelets. J Biol Chem. 1994;269:3397-3402.

8.

Atack JR, Rapoport SI, Varley CL. Characterization of inositol monophosphatase in human cerebrospinal fluid. Brain Res. 1993;613:305-308.

9.

Moyer JD, Reizes O, Dean NM, Malinowski N. D-myo-inositol (1,4)-bisphosphate 1-phosphate: partial purification from rat liver and characterization. Biochem Biophys Res Commun. 1987;146:1018-1026.

10.

Mitchell CA, Connolly TM, Majerus PW. Identification and isolation of a 75-kDa inositol polyphosphate-5-phosphatase from human platelets. J Biol Chem. 1989;264:8873-8877.

11.

Wissing J, Heim S, Wagner KG. Diacylglycerol kinase from suspension cultured plant cells: purification and properties. Plant Physiol. 1989;90:1546-1551.

12.

Kelley MJ, Carman GM. Purification and characterization of CDP-diacylglycerol synthase from Saccharomyces cerevisiae. J Biol Chem. 1987;262:14563-14570.

13.

Vargas LA, Li XM, Rosenthal AF. Inhibition of platelet phosphatidylinositol synthetase by an analog of CDP-diacylglycerol. Biochim Biophys Acta. 1984;796:123-128.

14.

Bhalla US, Iyengar R. Emergent properties of networks of biological signaling pathways. Science. 1999;283:381-387.

15.

Kinzer-Ursem TL, Linderman JJ. Both ligand- and cell-specific parameters control ligand agonism in a kinetic model of g protein-coupled receptor signaling. PLoS Comput Biol. 2007;3:e6.

16.

Waldo GL, Harden TK. Agonist binding and Gq-stimulating activities of the purified human P2Y1 receptor. Mol Pharmacol. 2004;65:426-436.

17.

Mukhopadhyay S, Ross EM. Rapid GTP binding and hydrolysis by G(q) promoted by receptor and GTPase-activating proteins. Proc Natl Acad Sci U S A. 1999;96:9539-9544.

†

Rate equation or kinetic parameters estimated de novo in this study.

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