In addition to providing increased structural stability to extracellular proteins, the reversible formation of disulfide bonds is utilized biologically in enzyme catalytic mechanisms, in the transport of reducing equivalents, in metabolic regulation, and as a cellular defense system (1-8). The interconversion of thiols and disulfides is an oxidation-reduction process, and as such, must be linked to suitable electron donors and acceptors (9, 10). Consequently, the circumstances under which disulfide bonds are formed and broken depends on the availability of electron donors and acceptors of appropriate redox potential and kinetic reactivity. The purpose of this chapter is to provide a kinetic and thermodynamic perspective on biological disulfide bond formation and disulfide bond reduction. While this is a rather narrow, and to some a frightening, view of an already complex biological problem, this approach will hopefully link the ability to form biological disulfide bonds to constraints imposed by the redox state of the environment in which disulfide bond formation occurs.

Following a presentation of basic kinetic and thermodynamic considerations, which apply to the chemistry of thiol-disulfide exchange, a variety of biological processes in which thiol-disulfide redox interconversion is thought to be important will be discussed. The latter discussion is organized along the lines of intracellular compartmentation in order to emphasize how little is actually known about the mechanisms that regulate the thiol-disulfide environment of various cellular compartments and because some sort of orga-