Department of Laboratory Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Laboratory of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
Glycobiology. 2019 May 1;29(5):366-371. doi: 10.1093/glycob/cwz014.
It is generally accepted that the biosynthesis of chondroitin sulfate and heparan sulfate is proceeding from a common linkage region tetrasaccharide comprising GlcA-Gal-Gal-Xyl-O-. The linkage region can undergo various modifications such as sulfation, phosphorylation and sialylation, and as the methods for studying glycosaminoglycan structure have been developed and refined, the number of discovered modifications has increased. Previous studies on the linkage region and the glycosyltransferases involved in the biosynthesis suggest that variants of the linkage region tetrasaccharide may also be possible. Here, using LC-MS/MS, we describe a non-canonical linkage region trisaccharide comprising GlcA-Gal-Xyl-O-. The trisaccharide was identified as a minor constituent in the proteoglycan bikunin from urine of human healthy donors present as a disulfated pentasaccharide, ΔHexA-GalNAc(S)-GlcA-Gal(S)-Xyl-O-, after chondroitinase ABC degradation. Furthermore, it was present as the corresponding disulfated pentasaccharide after chondroitinase ABC degradation in chondroitin sulfate primed on xylosides isolated from human cell lines. This linkage region trisaccharide may serve as an alternative point of entry for glycosaminoglycan biosynthesis.
人们普遍认为，硫酸软骨素和肝素硫酸的生物合成是从包含 GlcA-Gal-Gal-Xyl-O-的共同连接区四糖开始的。连接区可以进行各种修饰，如硫酸化、磷酸化和唾液酸化，随着研究糖胺聚糖结构的方法不断发展和完善，发现的修饰种类也在增加。先前对连接区和参与生物合成的糖基转移酶的研究表明，连接区四糖的变体也可能存在。在这里，我们使用 LC-MS/MS 描述了一种非典型的连接区三糖，由 GlcA-Gal-Xyl-O-组成。该三糖被鉴定为人类健康供体尿液中蛋白聚糖 bikunin 的少量成分，以二硫酸化五糖的形式存在，即ΔHexA-GalNAc(S)-GlcA-Gal(S)-Xyl-O-，在软骨素酶 ABC 降解后。此外，在人细胞系中分离的木糖苷预诱导的硫酸软骨素中，经软骨素酶 ABC 降解后，也存在相应的二硫酸化五糖。这种连接区三糖可能是糖胺聚糖生物合成的另一个起始点。
