Structures, function, and transformational changes of the sugar chains of glycohormones.
Human chorionic gonadotropin (hCG), human luteinizing hormone, human thyroid-stimulating hormone, and human follicle-stimulating hormone are closely related family of proteins which share a common alpha-subunit. However, their sugar moieties are quite different. hCG contains five acidic asparagine-linked sugar chains. These five sugar chains are derived by sialylation from three neutral oligosaccharides: two biantennary (N-1 and N-2) and one monoantennary (N-3) complex-type oligosaccharides. Although hCG purified from the urine of pregnant women is more enriched in sialylated sugar chains than that purified from placenta, the molar ratio of N-1, N-2, and N-3 of these two hCGs are the same (1:2:1). Comparative study of the sugar moieties of the alpha- and beta-subunits of hCG revealed that alpha contains 1 mol each of N-2 and N-3, while beta contains 1 mol each of N-1 and N-2. This specific distribution of oligosaccharides at the four asparagine loci of the hCG molecule is now helping us to consider the functional role of the sugar moiety of glycohormones. hCG is produced not only by the trophoblast but also by various trophoblastic diseases. The hCGs purified from the urine of patients with hydatidiform mole contain the same oligosaccharides as normal hCG. However, those from the urine of choriocarcinoma patients contain five additional neutral oligosaccharides. In contrast, hCGs from invasive-mole patients contain three of the five oligosaccharides, specifically found in choriocarcinoma hCGs. The malignant transformational change of the sugar moiety of hCG can be explained by an increase of a fucosyltransferase, which forms the Fuc alpha 1----6GlcNAc group and by ectopic expression and subsequent modification of N-acetylglucosaminyltransferase IV. The appearance of tumor-specific sugar chains of hCG has been used to develop a new diagnostic method for invasive mole and choriocarcinoma.
Kobata
A
A
Department of Biochemistry, University of Tokyo, Japan.
D001216:Asparagine / Q000032:analysis; D002240:Carbohydrate Sequence; D002822:Choriocarcinoma / Q000032:analysis; D006063:Chorionic Gonadotropin / Q000032:analysis* / Q000502:physiology; D005260:Female; D006023:Glycoproteins / Q000032:analysis* / Q000502:physiology; D006801:Humans; D006828:Hydatidiform Mole / Q000188:drug therapy; D008969:Molecular Sequence Data; D011247:Pregnancy; D014328:Trophoblastic Neoplasms / Q000032:analysis; D014594:Uterine Neoplasms / Q000032:analysis
D006063:Chorionic Gonadotropin; D006023:Glycoproteins; D001216:Asparagine