v V1 [S ] [S ]H 1 [S ]H 1 [S ]H 2 V1 V V 2 2 [ S ] K1 [ S ] H 1 K 2H 1 [ S ] H 1 K 2H 1 [ S ] H 2 K 3H 2 Terms used to define the production of -amyloid by -secretase (equation 5): v = reaction rate S = substrate V1 = maximum reaction rate at low substrate concentrations V2 = maximum reaction rate at high substrate concentrations K1 = substrate affinity term at low substrate concentrations K2 = substrate affinity term at high substrate concentrations K3 = substrate affinity term at high substrate concentrations which produce inhibition H1 = Hill coefficient used to define the substrate activation slope H2 = Hill coefficient used to define the substrate inhibition slope [ I ] Hx1 [ I ] Hx 2 [ I ] Hx 2 V1 V1 V1 V1is Hx1 V1 V1is Hx 2 V1 V1ii Hx 2 1 [ I ] K xHx [ I ] K xHx2 2 [ I ] K xHx2 2 1 Terms used to define DAPT modification of the V1 term: V1is =increase in reaction rate produced by low DAPT concentrations V1ii =decrease in reaction rate produced by high DAPT concentrations Kx1 = DAPT affinity binding term at low DAPT concentrations Kx2 = DAPT affinity binding term at high DAPT concentrations Hx1 = Hill coefficient used to define the DAPT activation slope Hx2 = Hill coefficient used to define the DAPT inhibition slope K1 K1 K1 K1is [ I ] Hx1 [ I ] Hx 2 [ I ] Hx 2 K K K K 1 1is 1 1ii [ I ] Hx1 K xHx1 1 [ I ] Hx 2 K xHx2 2 [ I ] Hx 2 K xHx2 2 Terms used to define DAPT modification of the K1 term: K1is =change in substrate affinity term produced by low DAPT concentrations K1ii = change in substrate affinity term produced by high DAPT concentrations Kx1 , Kx2, Hx1 and Hx2 are the same as above. [ I ] Hxx V2 V2 V2 V2i Hxx [ I ] K xxHxx 1 Terms used to define DAPT modification of the V2 term: V2i = decrease in reaction rate produced by DAPT Kxx1 = DAPT affinity binding term Hxx = Hill coefficient used to define the DAPT inhibition slope [ I ] Hxx K 2 K 2 K 2 K 2i Hxx [ I ] K xxHxx 1 Terms used to define DAPT modification of the K2 term: K2i = change in substrate affinity term produced by DAPT concentrations Kxx1 and Hxx are the same as above.