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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  · CCD95R · CCD95L, CCD95R 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 (kDISC_pro8 · Cpro8 · 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 · Ccasp3)
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 (kDISC_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 (kDFp8 · CDISC: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 (tC 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 ( k 8 Bid K m 8 Bid · C casp 8 · C Bid )
br22 Bid –casp8 → tBid (M-M) 100   
br23 Bid –casp2 → tBid (M-M) 10-1/100 br8* pro2 –casp3 → cleavage ( k 32 · C casp 3 · C pro 2 C pro 2 + K m 32 )
Blocking of IAP by Smac
br24 Smac stored → Smac (f release (tC 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 ( k 78 K m 78 · C casp 8 · 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 ( k 3 act K m 367 act · C casp 3 · 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 /Km367act + (1 − x aa ) · (k36act · Ccasp3 + k36act · Ccasp6 + k7act · Ccasp7)) 100 br13* x aa ( k 36 act + 0.18 · k 7 act K m 367 act · 1 x aa · C casp 3 )
  1. 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.