Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Matrix Biol. 2019 May;78-79:139-146. doi: 10.1016/j.matbio.2018.03.020. Epub 2018 Mar 27.
Hyaluronan (HA) is a glycosaminoglycan (GAG) composed of repeating disaccharide units of glucuronic acid and N-acetylglucosamine. HA is an extremely long, unbranched polymer, which often exceeds 10 Da and sometimes reaches 10 Da. A feature that epitomizes HA is its rapid turnover; one-third of the total body HA is turned over daily. The current model of HA catabolism postulates that high-molecular weight HA in the extracellular space is first cleaved into smaller fragments by a hyaluronidase(s) that resides at the cell surface, followed by internalization of fragments and their degradation into monosaccharides in lysosomes. Over the last decade, considerable research has shown that the HYAL family of hyaluronidases plays significant roles in HA catabolism. Nonetheless, the identity of a hyaluronidase responsible for the initial step of HA cleavage on the cell surface remains elusive, as biochemical and enzymological properties of HYAL proteins are not entirely consistent with those expected of cell surface hyaluronidases. Recent identification of transmembrane 2 (TMEM2) as a cell surface protein that possesses potent hyaluronidase activity suggests that it may be the "missing" cell surface hyaluronidase, and that novel models of HA catabolism should include this protein.
透明质酸（HA）是一种糖胺聚糖（GAG），由葡萄糖醛酸和 N-乙酰葡萄糖胺重复二糖单位组成。HA 是一种非常长的、无支链的聚合物，通常超过 10 Da，有时甚至达到 10 Da。HA 的一个显著特点是其快速周转；体内三分之一的总 HA 每天都在更新。目前的 HA 分解代谢模型假设，细胞外空间中的高分子量 HA 首先被位于细胞表面的透明质酸酶（s）切割成较小的片段，然后片段被内化，并在溶酶体中降解为单糖。在过去的十年中，大量研究表明，透明质酸酶家族在 HA 的分解代谢中发挥着重要作用。尽管如此，负责细胞表面 HA 切割初始步骤的透明质酸酶的身份仍然难以捉摸，因为 HYAL 蛋白的生化和酶学特性与细胞表面透明质酸酶的预期特性不完全一致。最近发现跨膜 2（TMEM2）作为一种具有强大透明质酸酶活性的细胞表面蛋白，表明它可能是“缺失”的细胞表面透明质酸酶，新型 HA 分解代谢模型应该包括这种蛋白。
