Hyaluronan synthase

Hyaluronan synthases (HAS) are membrane-bound enzymes which use UDP-α-N-acetyl-D-glucosamine and UDP-α-D-glucuronate as substrates to produce the glycosaminoglycan hyaluronan at the cell surface and extrude it through the membrane into the extracellular space.

Isoforms
There are three mammalian hyaluronan synthases described to date -, and. Each of these isoforms resides at a different chromosome location and has been cloned. Two of the main differences between the isoforms are the chain length of the hyaluronan molecules that they produce and the ease with which they can be released from the cell surface. When mammalian cells are stimulated by changes in their immediate environment (cytokines, extracellular matrix proximities), the HAS isoforms respond differently and appear to be under different control mechanisms.

During the development of the embryo, each isoform is uniquely expressed, both spatially and temporally.
 * HAS2 is probably the most important synthase at this time as mice lacking the ability to express HAS2 (knock-out mice) die at mid-gestation,
 * HAS1 or HAS3 knock-out mice show no effect on foetal development.