Catabolism of hyaluronan: involvement of transition metals

Abstract

One of the very complex structures in the vertebrates is the joint. The main component of the joint is the synovial fluid with its high-molar-mass glycosaminoglycan hyaluronan, which turnover is approximately twelve hours. Since the synovial fluid does not contain any hyaluronidases, the fast hyaluronan catabolism is caused primarily by reductive-oxidative processes.Eight transition metals - V(23), Mn(25), Fe(26), Co(27), Ni(28), Cu(29), Zn(30), and Mo(42) - naturally occurring in living organism are essential for the control of various metabolic and signaling pathways. They are also the key elements in catabolism of hyaluronan in the joint.In this overview, the role of these metals in physiological and pathophysiological catabolism of hyaluronan is described. The participation of these metals in the initiation and propagation of the radical degradation hyaluronan is critically reviewed.

Keywords: hyaluronan catabolism; joint; oxidative stress; peroxidation; synovial fluid; transition metals.

Scheme 1

Generation of H₂O₂ by Weissberger's system from ascorbate and Cu(II) under aerobic conditions (adapted from Fisher and Naughton, 2005).

Figure 1

Hyaluronan – the acid form.

Scheme 2

AO· strand scission may be due to β-cleavage of the radical formed at, e.g. C(1) on the ring of D-glucuronate/D-glucuronic acid.

Figure 2

Time dependences of dynamic viscosity of hyaluronan (P9710-2A) sample solutions (2.5 mg/mL). Left panel: Solutions of the HA sample with addition of 100 µM ascorbic acid immediately followed by admixing 0.5 or 5.0 µM of FeCl2. Middle panel: Solutions of the HA sample with addition of 100 µM ascorbic acid immediately followed by admixing 0.1 or 5.0 µM of CuCl2. Right panel: The curve represents an assay, in which 0.1 µM of CuCl2 was added to the HA sample solution 9 minutes before admixing 100 µM ascorbic acid (for details see Šoltés et al., 2007).

Figure 3

Comparison of MMD of the megadalton HA sample and those degraded in situ by oxygen-derived reactive species (cf. also Figure 2 and Ref. Šoltés et al., 2007).