PathwayStep1023 PathwayStep1029 PathwayStep1028 PathwayStep1027 PathwayStep1026 PathwayStep1025 PathwayStep1024 PathwayStep1031 PathwayStep1030 Hyaluronan uptake and degradation Authored: Jassal, B, 2012-03-05 Edited: Jassal, B, 2012-03-05 GENE ONTOLOGYGO:0030214 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.<br>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). ISBN9780080443829 Pubmed14514708 Pubmed22216413 Pubmed9839614 Reactome Database ID Release 432160916 Reactome, http://www.reactome.org ReactomeREACT_120996 Reviewed: D'Eustachio, P, 2012-03-28 Beta-glucuronidase (GUSB) hydrolyses glucuronate from HA tetrasaccharides Beta-hexosaminidase A (BHEXA) cleaves the terminal GalNAc from small HA fragments Beta-glucuronidase (GUSB) hydrolyses glucuronate from the HA disaccharides The single sugars GlcA and GlcNAc translocate from the lysosome to the cytosol 20kDa HA fragments are translocated to lysosomes Hyaluronidase 2 (HYAL2) hydrolyses HA into 20kDa fragments Hyaluronidase 1 (HYAL1) hydrolyses HA from 20kDa to 800Da fragments HYAL2 interacts with NHE1 to create an acidic environment Receptor-mediated uptake of HA