Structural and Related Studies

Hyaluronic acid, a mucopolysaccharide composed of alternate units of N-acetylglucosamine and D-glucuronic acid, is found in the ground substance of many connective tissues. Umbilical cord (Ml), pseudo- 

The structure of hyaluronic acid is now well established. Acidic hydrolysis yields the constituent disaccharide, hyalobiouronic acid, whose structure was shown to be 2-amino-2-deoxy-3-0-(P-D-glucopyranosylu-ronic acid)-D-glucose by degradative studies (W3) and, more recently, by constitutional syntheses (J7, Tl). The hexosaminidic linkage has been shown to have a pi- 4 configuration by enzyme (W4) and methylation (Hll) studies, so that hyaluronic acid may be assigned structure (1). 

The large size of the hyaluronic acid molecules and their random-coil configuration lead to molecular interactions, even in dilute solution. As a result of these interactions, solutions of the polymer exhibit non-Newtonian and elastoviscosity (Bll). Synovial fiuid shows an increase in viscosity with reduced shearing force and possesses structural rigidity which is reversibly broken down by shearing. Such viscosity behavior makes synovial fluid an ideal lubricant between joint surfaces, which move slowly under considerable pressure for most of the time but which may be required to accelerate violently (03). 

Another important consequence of the interpenetration of hyaluronic acid chains is that, at rest, their solution may be considered as a continuous network of large molecules (04). Such a structure oflEers resistance to flow and, while the rate of difiFusion of small molecules through the mesh is comparatively little affected, the diffusion of larger molecules, approaching in size that of the mesh, is impeded. Fessler (FI) considers that these effects might also be considered as a possible function of hyaluronic acid in connective tissues. 

Other possible physiological functions of hyaluronic acid may be associated with its macroanionic nature. Aldrich (A4), for example, observed that Ca++ was strongly associated with a hyaluronic acid-protein complex, and was not readily displaced by high concentrations of univalent cations. A possible role for hyaluronic acid in regulating the concentrations of Na+ and K+ in nerve fibers has also been suggested (Al). 

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