Is there any physiological role for gonadotrophin oligosaccharide heterogeneity in humans? II. A biochemical point of view.
Heterogeneity of gonadotrophin oligosaccharides caused either by pharmacological intervention or which occurs naturally during normal physiological changes is well documented. Recent advances in structure determination of oligosaccharides has to some extent led to a better appreciation of how oligosaccharide heterogeneity may affect protein folding, stability, measurement and modulation of receptor binding. Here it is discussed how carbohydrate structure can impact upon gonadotrophin structure and function. It is well documented that oligosaccharides can serve as a cognate site for protein binding. One functional aspect of gonadotrophin glycosylation heterogeneity is the modulation of receptor binding affinity, yielding partially agonistic glycoforms. Carbohydrate heterogeneity is problematic for a clinical chemist if immunochemical assays are sensitive to heterogeneity. However, even measurements made without such interference may not accurately reflect the biological activity that is a collective result of all isoforms in the circulation, and perhaps of the genotype of each individual. Moreover, oligosaccharide heterogeneity may affect heterodimer stability, therefore, biological activity and immunochemical activity, not to mention clearance. It seems reasonable to conclude that from a biochemical point of view, oligosaccharide heterogeneity is of considerable importance. However, accurate measurement of isoforms in blood, and appropriate in-vitro bioassays that are insensitive to matrix effects are needed to define the physiological significance of each glycoform, and thereby better define target therapeutics and interpret diagnostic results.
Dias
J A
JA
Wadsworth Center, New York State Department of Health, David Axelrod Institute for Public Health, 120 New Scotland Avenue, Albany, NY, USA.
D001665:Binding Sites; D002240:Carbohydrate Sequence; D006063:Chorionic Gonadotropin / Q000737:chemistry / Q000502:physiology; D006031:Glycosylation; D006062:Gonadotropins / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D009844:Oligosaccharides / Q000737:chemistry*; D011485:Protein Binding; D017510:Protein Folding; D013329:Structure-Activity Relationship
D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D009844:Oligosaccharides