Enzymatic reduction-oxidation of protein disulfides by thioredoxin

Abstract

Thioredoxin and the associated enzyme, thioredoxin reductase, constitute a thiol-dependent reduction–oxidation system that can catalyze the reduction of certain disulfides by nicotinamide adenine dinucleotide phosphate hydrogenase (NADPH). This chapter provides an overview of the occurrence and structure-function relationships of thioredoxin and thioredoxin reductase. The thioredoxin system is composed of three components: NADPH, thioredoxin reductase, and thioredoxin. The reduction of disulfide bonds by the thioredoxin system has so far been described only for a limited number of proteins—namely, insulin, fibrinogen and fibrin, choriogonadotropin, and coagulation factor VIII and other coagulation factors in plasma. The reduction of disulfide bonds by the thioredoxin system has several advantages when compared with the chemical methods for the reductive cleavage of disulfide bonds employing 2-mercaptoethanol or dithiothreitol (DTT). However, it has also some limitations. The thioredoxin system from E. coli is superior to the systems from mammalian cells that are more difficult to purify and measure, owing to the easy inactivation by the oxidation of structural SH groups.