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Carbohydrate abnormalities of N-linked plasma glycoproteins in liver disease.

  • Martinéz, J
  • Barsigian, C
Published Article
Laboratory investigation; a journal of technical methods and pathology
Publication Date
Sep 01, 1987
PMID: 3306148


Glycoproteins are proteins with covalently attached carbohydrate which is enzymatically added during the biosynthesis of the polypeptide. Attachment of carbohydrate to the polypeptide may involve either an N-glycosidic or an O-glycosidic bond. Most of the plasma glycoproteins have N-linked oligosaccharides attached to appropriate asparagine moieties of the peptide core. The biosynthesis of the N-linked glycoproteins proceeds through three sequential phases which include (a) dolichol-mediated oligosaccharide assembly, (b) oligosaccharide linkage to the polypeptide, and (c) oligosaccharide processing with the addition of peripheral sugars. Much of the diversity in carbohydrate structure of plasma glycoproteins results from variations in processing and addition of peripheral sugars. The terminal monosaccharide of N-linked plasma glycoproteins is usually sialic acid, a negatively charged sugar which markedly affects the physicochemical and biologic characteristics of glycoproteins. Liver disease induces alterations in both the level and structure of many plasma glycoproteins, particularly those which are synthesized by the hepatocyte. Quantitative changes in the concentration of plasma glycoproteins are relatively easy to assess due to the availability of many types of clinical assays. Furthermore, quantitation of the level of a particular glycoprotein in the plasma often provides clinically useful information pertinent to diagnosis and progression of disease. The determination of functional abnormalities of glycoproteins and the correlation of these functional changes with potential alterations in carbohydrate structure is more difficult, however, due to the need for accurate functional assays and sophisticated methods for analysis of the carbohydrate structure of the abnormal molecules, which are themselves often scarce. Liver disease-induced alterations in the oligosaccharide moieties of plasma glycoproteins involve mainly hyperglycosylation or hypoglycosylation defects. These changes can often be traced to increases or decreases in the amount of sialic acid present within the abnormal structure. Since sialic acid plays such a key role in the biology of glycoproteins, changes in the amount of this monosaccharide frequently result in marked alterations in the physicochemical and biologic behavior of the abnormal molecule. The exact mechanisms responsible for the changes in sialic acid are not entirely known, since the complete oligosaccharide structure of any of the abnormal glycoproteins of liver disease has not been determined.(ABSTRACT TRUNCATED AT 400 WORDS)

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