Iduronic

Idurononic acid, commonly referred to as iduronic acid (IdoA), is a uronic sugar that occurs in glycosaminoglycans, most notably in the form of L-iduronic acid. It is the C-5 epimer of D-glucuronic acid and commonly found within proteoglycans such as dermatan sulfate and heparan sulfate.

During glycosaminoglycan biosynthesis, glucuronic acid residues can be converted to iduronic acid by glucuronyl C5-epimerase, generating IdoA-containing disaccharides. The iduronic residues can also be sulfated at the 2-O position, contributing to the overall sulfation pattern that governs interactions with proteins and other matrix components.

Iduronic acid residues confer conformational flexibility to glycosaminoglycan chains, influencing their three-dimensional structure and their ability to interact with a range of proteins, including growth factors, cytokines, and extracellular matrix components. The negative charge from carboxylate groups and sulfates promotes hydration and facilitates binding to cations and water networks, which helps determine the physical properties of connective tissues.

Clinically, deficiency of the lysosomal enzyme iduronidase (encoded by the IDUA gene) leads to the accumulation of iduronate-containing glycosaminoglycans and causes mucopolysaccharidosis type I (Hurler syndrome). This highlights the biological importance of iduronic acid-containing GAGs in normal lysosomal degradation and connective tissue homeostasis.