Reactome | Hyaluronan degradation

Hyaluronan degradation

Stable Identifier

R-HSA-2160916

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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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.
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 (Lepperdinger et al. 2004, Menzel & Farr 1998, Erickson & Stern 2012, Stern 2003).

There are seven different hyaluronidases (HAases) in humans: HYAL1, HYAL2, HYAL3, SPAM1, and CEMIP (reviewed in Liu et al., 2024).

Literature References

PubMed ID	Title	Journal	Year
37953485	Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential Liu, Z, Hou, P, Fang, J, Shao, C, Shi, Y, Melino, G, Peschiaroli, A	Mol Oncol	2024
	Chemistry and Biology of Hyaluronan Garg, HG, Hales, CA		2004
14514708	Devising a pathway for hyaluronan catabolism: are we there yet? Stern, R	Glycobiology	2003
9839614	Hyaluronidase and its substrate hyaluronan: biochemistry, biological activities and therapeutic uses Menzel, EJ, Farr, C	Cancer Lett	1998
22216413	Chain gangs: new aspects of hyaluronan metabolism Erickson, M, Stern, R	Biochem Res Int	2012