Mucoprotein disulfide bonds

Mucoprotein disulfide bonds are the critical covalent cross-links that stabilize the polymeric structure of respiratory mucins, specifically MUC5AC and MUC5B (Thornton et al., 2008, Annu Rev Physiol). These bonds are formed between cysteine-rich domains of mucin monomers, creating a high-molecular-weight network that determines the viscoelastic properties of airway mucus (Fahy & Dickey, 2010, N Engl J Med). In healthy individuals, this gel-like consistency is essential for the mucociliary escalator to trap and remove inhaled particles and pathogens. However, in diseases like cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), the density of these disulfide bonds increases due to mucus hypersecretion and oxidative stress, leading to stagnant, thick mucus that obstructs the airways (Button et al., 2012, Science). Pharmacological targeting of these bonds is achieved through mucolytic agents like N-acetylcysteine (NAC), which possess a free sulfhydryl group that participates in a disulfide-sulfhydryl exchange reaction (Sadowska, 2012, Proc Am Thorac Soc). This reaction breaks the mucin polymers into smaller subunits, significantly reducing mucus viscosity and elasticity to facilitate clearance and improve respiratory function (Aldini et al., 2018, Free Radic Res).

Other names

Mucin disulfide bondsMucoprotein disulfide bridgesMucin cross-linksInter-mucin disulfide linkages

Reduction of inter-mucin disulfide bridges via sulfhydryl-disulfide exchange, leading to the depolymerization of mucin networks and reduction of mucus viscosity (StatPearls, 2023; Sadowska, 2012).