Biological Synthesis and Degradation of Hyaluronic Acid

Hyaluronic acid is synthesized by a class of integral membrane proteins called hyaluronan synthases, whose vertebrates have three types: HAS1, HAS2 and HAS3. These enzymes lengthen hyaluronan by repeatedly adding glucuronic acid and N-acetylglucosamine to the nascent polysaccharide as it is extruded via the ABC transporter across the cell membrane into the extracellular space.

The synthesis of hyaluronic acid has been shown to be inhibited by 4-methylumbelliferone, a derivative of 7-hydroxy-4-methylcoumarin. This selective inhibition may be useful for preventing the metastasis of malignant tumor cells. There is a feedback inhibition of hyaluronan synthesis by low molecular weight hyaluronan at high concentrations but stimulation by high molecular weight HA in tests in human synovial fibroblasts in culture. Bacillus subtilis has recently been genetically engineered to develop a patented formula for producing hyaluronans in a patented process producing a human grade product.

Also read : 9 things you should know about hyaluronic acid!

 
Hyaluronic acid can be broken down by a family of enzymes called hyaluronidases. In humans, there are at least seven types of hyaluronidase enzymes, many of which are tumor suppressors. The degradation products of hyaluronan, oligosaccharides and hyaluronan of very low molecular weight have pro-angiogenic properties. In addition, recent studies have shown that hyaluronan fragments, and not the high molecular weight native molecule, can induce inflammatory responses in macrophages and dendritic cells in tissue lesions and in skin transplantation. Hyaluronic acid can also be degraded by non-enzymatic reactions. These include acid and alkaline hydrolysis, ultrasonic disintegration, thermal decomposition and oxidative degradation.

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