Model composition through model reduction: a combined model of CD95 and NF-κB signaling pathways

Kutumova, Elena; Zinovyev, Andrei; Sharipov, Ruslan; Kolpakov, Fedor

doi:10.1186/1752-0509-7-13

BMC Systems Biology

Table 1 Summary of reactions from the original model by Bentele et al. and the reduced model

From: Model composition through model reduction: a combined model of CD95 and NF-κB signaling pathways

Original model			Reduced model
№	Reactions (Kinetics)	Rates (nM/min)	№	Reactions (Kinetics)
*Activation of caspase-8 induced by CD95*
br1	CD95L + CD95R → СD95R:СD95L (MA)	10¹/10⁰	br1*	CD95L → DISC (k_LR · C_CD95R · C_CD95L, C_CD95R is determined by the formula (14))
br2	FADD + СD95R:СD95L → DISC (MA)	10¹/10⁰
br3	pro8 + DISC → DISC:pro8 (MA)	10⁰/10^-1
br4	pro8 + DISC:pro8 → DISC:pro8₂ (MA)	10⁰/10^-1
br5	DISC:pro8₂ → DISC:p43/p41 (MA)	10⁰/10^-1	br2*	pro8 –DISC → casp8 (k_{DISC_pro8} · C_pro8 · C_DISC)
br6	DISC:p43/p41 → casp8 + DISC (MA)	10⁰/10^-1
*Activation of caspase-8 by caspase-3*
br7	pro6 -casp3 → casp6 (M-M)	10⁰/10^-1	br3*	pro8 –casp3 → casp8 (k₃₈ · C_casp3)
br8	pro8 -casp6 → casp8 (M-M)	10^-1/10⁰
*Inhibition of the DISC complex*
br9	DISC + cFLIPL → DISC:cFLIPL (MA)	10¹/10⁰	br4*	cFLIP + 2·DISC + pro8 → DISC:FLIP:pro8 (k_{DISC_FLIP} · C_FLIP · C_DISC)
br10	pro8 + DISC:cFLIPL → DISC:cFLIPL:pro8 (MA)	10⁰
br11	DISC + cFLIPS → blocked DISC (MA)	10¹/10⁰
br12	DISC:pro8 + cFLIPL → DISC:cFLIPL:pro8 (MA)	10^-2/10^-3	br5*	DISC:FLIP:pro8 → p43/p41 (k_DFp8 · C_{DISC:FLIP:pro8})
br13	DISC:pro8 + cFLIPS → blocked DISC (MA)	10^-2/10^-3
br14	DISC:cFLIPL:pro8 → p43/p41 + blocked DISC (MA)	10^-1
*Activation of caspase-9 triggered by cytochrome C*
br15	Cyt C stored → Cyt C (f_release(t)·C_CytCstored)	10²	br6*	pro9 → cleavage (the formula (16))
br16	Apaf-1 + Cyt C → Cyt C:Apaf-1 (MA)	10²
br17	Cyt C:Apaf-1 → Apaf-1 + Cyt C (MA)	10¹
br18	pro9 + Cyt C:Apaf → Apop (MA)	10⁰
br19	Apop -casp3 → casp9 + Cyt C:Apaf-1	10⁰
	(M-M)
br20	Apop → casp9 + Cyt C:Apaf-1 (MA)	10^-2
*Activation of Bid*
br21	pro2 –casp3 → casp2 (M-M)	10⁰	br7*	Bid –casp8 → tBid ( $\frac{k_{8 Bid}}{K m_{8 Bid}} \cdot C_{casp 8} \cdot C_{Bid}$ )
br22	Bid –casp8 → tBid (M-M)	10⁰
br23	Bid –casp2 → tBid (M-M)	10^-1/10⁰	br8*	pro2 –casp3 → cleavage ( $\frac{k_{32} \cdot C_{casp 3} \cdot C_{pro 2}}{C_{pro 2} + K m_{32}}$ )
*Blocking of IAP by Smac*
br24	Smac stored → Smac (f_release(t)·C_{Smac stored})	10²	–
br25	Smac + IAP → IAP:Smac (MA)	10^-5
br26	IAP:Smac → Smac + IAP (MA)	10^-5
*Activation of caspases-3 and −7*
br27	pro3 –casp8 → casp3 (M-M)	10¹/10⁰	br9*	pro3 –casp8 → casp3 (M-M)
br28	pro3 –casp9 → casp3 (M-M)	10^-3/10⁰
br29	pro7 –casp8 → casp7 (M-M)	10⁰/10^-1	br10*	pro7 –casp8 → cleavage ( $\frac{k_{78}}{K m_{78}} \cdot C_{casp 8} \cdot C_{pro 7}$ )
br30	pro7 –casp9 → casp7 (M-M)	10^-5/10^-3
*PARP inactivation*
br31	PARP -casp3 → cPARP (М-М)	10^-1	br11*	PARP -casp3 → cPARP ( $\frac{k_{3 act}}{K m_{367 act}} \cdot C_{casp 3} \cdot C_{PARP}$ )
br32	PARP –casp7 → cPARP (М-М)	10⁰/10^-1
*Inhibition of caspases-3, -7 and −9*
br33	casp3 + IAP → casp3:IAP (МA)	10⁰	br12*	casp3 + IAP → inhibition (MA)
br34	casp7 + IAP → casp7:IAP (МA)	10^-1
br35	casp9 + IAP → casp9:IAP (МA)	10^-3
br36	casp3:IAP → casp3 + IAP (МA)	10^-2
br37	casp7:IAP → casp7 + IAP (МA)	10^-4/10^-3
br38	casp9:IAP → casp9 + IAP (МA)	10^-5/10^-4
*Production of the virtual variable* x _aa
br39	→ x_aa (1 − x_aa/Km_367act + (1 − x_aa) · (k_36act · C_casp3 + k_36act · C_casp6 + k_7act · C_casp7))	10⁰	br13*	→ x_aa ( $\frac{k_{36 act} + 0.18 \cdot k_{7 act}}{K m_{367 act}} \cdot (1 - x_{aa}) \cdot C_{casp 3}$ )

Prototypes of parameter notations in the original Bentele’s model are listed in Additional file 1: Table 1S. Abbreviations used in the table represent МA – mass action kinetics and M-M – Michaelis-Menten kinetics. The column with rates includes rate orders for the fast/reduced activation scenarios.

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ISSN: 1752-0509

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