Pathway
Hyaluronan degradation
Hyaluronan (HA) turnover can occur locally at the tissue of origin, where it is taken up by cells to be degraded, or released into the lymphatic and vascular systems, where it can be eliminated by the liver and kidneys. Uptake of HA into cells for degradation involves receptor-mediated processes. Once HA enters lysosomes, the acidic conditions favour hyaluronidases to cleave it into small oligosaccharides, the most common size being a tetrasaccharide. Beta-glucuronidases participate in degrading the small oligosaccharides in the lysosome. Ultimately, HA is degraded into its constituent sugars (glucuronic acid and N-acetylglucosamine) which can be used to reform many glycosaminoglycans (GAGs) when released from the lysosome.
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A third of the total HA content in humans is turned over daily and it has a short half life of minutes in circulation up to days in many tissues. The reasons why the body eliminates HA so rapidly are unknown but one possible explanation could be HA's role as a reactive oxygen species (ROS) scavenger. Removing these toxic compounds could explain the rapid elimination of HA.
There are seven different hyaluronidases (HAases) in humans: HYAL1, HYAL2, HYAL3, SPAM1, and CEMIP (reviewed in Liu et al., 2024).
What the reference databases state
Statements
16 statements
16 statements · 1 reference database · Subject: Hyaluronan degradation · Sources: Reactome
- CD44 participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- CEMIP participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- CHP1 participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- GUSB participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- HEXA participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- HEXB participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- HMMR participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- HYAL1 participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- HYAL2 participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- HYAL3 participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- HYAL4 participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- LYVE1 participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
Show the remaining 4
- SLC17A5 participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- SLC9A1 participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- SPAM1 participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only
- STAB2 participates in Hyaluronan degradationProteinReactome R-HSA-2160916Inferred only