A MODEL FOR THE UNUSUAL KINETICS OF THERMAL-DENATURATION OF RUBREDOXIN

The thermal denaturation of the simple, redox-active iron protein rubr edoxin is characterized by a slow, irreversible decay of the character istic red color of the iron center at elevated temperatures in the pre sence of oxygen at pH 7.8. The denaturation rate is essentially consta nt and the time period for complete bleaching is nearly independent of protein concentration. These two characteristics of the kinetics can be fit by a simple self-catalyzed kinetics model consisting of the com bination of a first-order decay and catalysis by some product of that decay, i.e., dP/dt=k(1)[A] + (k(2)[P][A])I(K-m + [Al]), where A is nat ive rubredoxin, P, is unspecified product, k(1) is a first-order rate constant, and k(2) and K-m are the catalytic constants. In order for t he second term to be of this simple form over the full course of a dec ay, the model must include the condition that the reaction is effectiv ely irreversible. This model has properties which suggest other biolog ical roles in regulation (changes in k(1) or k(2) can dramatically mod ulate the kinetics), in timing (titer-independent fixed reaction time) , and in self-activation reactions. At one extreme (k(1) much greater than k(2)) the kinetics becomes exponential, but at the other extreme (k(2) much greater than k(1)) they show a dramatic and rapid terminal increase after a lag period. Some obvious possible roles in the kineti cs of programmed cell death, prion disease, and protease autoactivatio n are discussed.