hyaluronidases

Hyaluronidases are a family of enzymes that catalyze the hydrolysis of hyaluronic acid, a large glycosaminoglycan that is a major component of the extracellular matrix in vertebrates. By breaking down hyaluronan, these enzymes reduce the viscosity of the extracellular matrix and increase tissue permeability, facilitating the dispersion of molecules through tissues.

In humans, several hyaluronidases are recognized, including HYAL1, HYAL2, HYAL3, HYAL4, and SPAM1 (also known as PH-20). These enzymes differ in cellular localization and activity: some are lysosomal enzymes involved in hyaluronan turnover, while others are membrane-associated or secreted and function to remodel the extracellular matrix in specific contexts such as reproduction. A variety of microorganisms, as well as venoms, also produce hyaluronidases that act as virulence factors to promote spread through host tissues.

Mechanistically, hyaluronidases cleave internal β-1,4 glycosidic bonds within hyaluronan, producing smaller fragments and lowering the viscosity of the matrix. This activity can facilitate cell movement, tissue remodeling, and diffusion of nutrients or pathogens. The enzymes can have different pH optima and substrate specificities, reflecting their diverse biological roles.

Medical and biotechnological relevance is significant. Hyaluronidase is used clinically as a spreading factor to enhance diffusion of injected drugs or fluids, improve the dispersion of local anesthetics, and treat extravasation injuries. It is also used to dissolve hyaluronic acid-based dermal fillers. Sources include animal-derived preparations and recombinant forms. Possible adverse effects include allergic reactions and hypersensitivity, underscoring the need for appropriate assessment prior to use.