Fig. 1.

The bio-synthesis of HA. The process of HA synthesis in the ‘Pendulum’ movement pathway starts from the initiation of the leading signal, a chitin primer connecting 6 constant GlcNAc. Two substrates of UDP-sugars, UDP-GlcNAc and UDP-GlcUA were recruited to the membrane, and generated linear polymers connecting with GlcUA-(1,3)-GlcNAc -β(1,4)-GlcUA-bond. The residue addition synthesis was produced inside the HAS, and was delivered by transferase under Mg²⁺ catalysis. The HA polymers were extruded through intra-protein pore of HAS, hanging out of the extracellular space nearby the membrane or folding as tangle through the intra-molecular and intermolecular H-bonds. Different HA receptors recognized specific HA polymers with different molecule weights. For example, CD44 captured HMW-HA and formed HA ‘coat’ on the external surface of cells. The lower left box with dash line indicates the detail and specific position of HAS how it produces the HA synthesis. The lower right box with the dash line indicates the working requirement and products of HA synthesis when three HAS isoforms, HAS1, HAS2, HAS3, start dynamic regulation