Insulin and antibodies rely on disulfide bridges between cysteine residues, yet cysteines in cytosolic proteins stay unbonded even when neighbors could pair. What explains this split behavior?

Core Concept

Disulfide formation strips two sulfhydryl groups of electrons, an oxidation that proceeds readily in the oxidizing ER lumen with help from enzymes such as protein disulfide isomerase. The cytosol maintains abundant reducing agents, including glutathione, that keep cysteine thiols protonated and separate. Compartmental redox chemistry, not substrate availability, decides where these bridges appear.