Hyaluronidase

Hyaluronidases are a family of enzymes that catalyse the degradation of hyaluronic acid. Karl Meyer classified these enzymes in 1971, into three distinct groups, a scheme based on the enzyme reaction products. The three main types of hyaluronidases are two classes of eukaryotic endoglycosidase hydrolases and a prokaryotic lyase-type of glycosidase. In humans, there are five functional hyaluronidases: HYAL1, HYAL2, HYAL3, HYAL4 and HYAL5 (also known as SPAM1 or PH-20); plus a pseudogene, HYAL6 (also known as HYALP1). The genes for HYAL1-3 are clustered in chromosome 3, while HYAL4-6 are clustered in chromosome 7. HYAL1 and HYAL2 are the major hyaluronidases in most tissues. GPI-anchored HYAL2 is responsible for cleaving high-molecular weight hyaluronic acid, which is mostly bound to the CD44 receptor. The resulting hyaluronic acid fragments of variable size are then further hydrolyzed by HYAL1 after being internalized into endo-lysosomes; this generates hyaluronic acid oligosaccharides. Hyaluronidases are hyaluronoglucosidases (EC 3.2.1.35), i.e. they cleave the (1→4)-linkages between N-acetylglucosamine and glucuronate. The term hyaluronidase may also refer to hyaluronoglucuronidases (EC 3.2.1.36), which cleave (1→3)-linkages. In addition, bacterial hyaluronate lyases (EC 4.2.2.1) may also be referred to as hyaluronidases, although this is uncommon.