Formation kinetics of insulin-based amyloid gels and the effect of added metalloporphyrins.
The kinetics of insulin-based amyloid gel formation has been studied using extinction and fluorescence detection. The process is treated as autocatalytic, and the kinetic profiles are fit using a nonconventional analysis involving a time-dependent rate constant (factor): k(t) = k(o) + k(c)(k(c)t)(n). The dependence of the kinetic parameters on initial solution conditions of concentration, pH, and ionic strength has been investigated. A mechanism is proposed in which the rate-determining step involves the activation of insulin solute species into partially unfolded, structurally modified monomers, which then aggregate. The influence of added metalloporphyrins on the rate and extent of gel formation is described. Metal derivatives of tetrakis(4-sulfonatophenyl)porphine prove effective at inhibiting the aggregation of insulin via pathways that depend on concentration and identity of the incorporated metal.
Pasternack
Robert F
RF
Department of Chemistry & Biochemistry, Swarthmore College, Swarthmore, Pennsylvania, USA. rpaster1@swarthmore.edu
Gibbs
Esther J
EJ
Sibley
Scott
S
Woodard
Lauren
L
Hutchinson
Peter
P
Genereux
Joseph
J
Kristian
Kathleen
K
D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D002384:Catalysis; D002417:Cattle; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D005782:Gels / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry* / Q000378:metabolism; D007477:Ions; D007700:Kinetics; D008665:Metalloporphyrins / Q000737:chemistry*; D008956:Models, Chemical; D010179:Pancreas / Q000378:metabolism*; D011166:Porphyrins / Q000737:chemistry; D011489:Protein Denaturation; D017510:Protein Folding; D013997:Time Factors
D000682:Amyloid; D005782:Gels; D007328:Insulin; D007477:Ions; D008665:Metalloporphyrins; D011166:Porphyrins