Catabolism of chondroitin sulfate

Abstract

Chondroitin sulfate (CS) is a ubiquitous component of the cell surface and extracellular matrix of animal tissues. CS chains are covalently bound to a core protein to form a proteoglycan, which is involved in various biological events including cell proliferation, migration, and invasion. Their functions are executed by regulating the activity of bioactive proteins, such as growth factors, morphogens, and cytokines. This review article focuses on the catabolism of CS. This catabolism predominantly occurs in lysosomes to control the activity of CS-proteoglycans. CS chains are fragmented by endo-type glycosidase(s), and the resulting oligosaccharides are then cleaved into monosaccharide moieties from the nonreducing end by exoglycosidases and sulfatases. However, the endo-type glycosidase responsible for the systemic catabolism of CS has not yet been identified. Based on recent advances in studies on hyaluronidases, which were previously considered to be hyaluronan-degrading enzymes, it appears that they recognize CS as their original substrate rather than hyaluronan and acquired hyaluronan-hydrolyzing activity at a relatively late stage of evolution.

Molecular interactions between chondroitin–dermatan sulfate and growth factors/receptors/matrix proteins

“…CS chains are covalently bound to a core protein to form CS proteoglycans, which are widely distributed in the animal kingdom [2]. The functions of CS proteoglycans cover a wide range of biological events [3-5,6 ,7 ], some of which are executed through interactions with various bioactive protein components including growth factors, morphogens, cytokines, and cell adhesion molecules [1,3,4]. Although CS is composed of a simple repeat of the disaccharide unit [-4-D-glucuronic acid (GlcA)b1-3-N-acetyl-D-galactosamine (GalNAc)b1-], it acquires vast structural variations due to modifications with the sulfation of hydroxyl groups at the C4 and C6 positions of GalNAc and C2 position of the GlcA residues as well as epimerization at the C5 position of GlcA residue to form L-iduronic acid (IdoA) (Figure 1).…”

Biocompatible superparamagnetic carriers of chondroitin sulfate

“…6, may indicate a modulation of the release of ChS, as its coordination with the ION surface must be cleaved before to be catabolized. Moreover, the catabolism of chondroitin sulfate has been investigated [59] showing that ChS degradation occurs predominantly in lysosomes after endocytosis involving a large quantity of enzymes. Its depolymerization begins with endo-type hydrolases and the resulting…”

Identification and Signature Sequences of Bacterial Δ4,5Hexuronate-2-O-Sulfatases

“…GAG sulfatases with distinct degradation patterns play a vital role in polysaccharide degradation, during which endo-sulfatases remove sulfate groups from GAGs to facilitate the cleavage of polysaccharide chains by GAG-degrading enzymes (Wang et al, 2015). The resulting oligosaccharides, particularly disaccharides, are further desulfated by exo-sulfatases and subsequently hydrolyzed by glucuronyl hydrolases to produce monosaccharides and sulfates, which may be used as carbon and sulfur sources for cell growth (Ernst et al, 1995; Yamada, 2015).…”