Glycosylation of collagen

Investigative studies on the nonenzymatic glycosylation of collagen have elucidated several aspects of its effect in altering the structural and functional properties of collagens. In rats rendered diabetic, examination of tail... 

B32. Brownlee, M., Vlassara, H., and Cerami, A., Reactive products generated by nonenzymatic glycosylation of collagen covalently trap low density lipoprotein. Di-abetologia 27, 260A, Abstr. 63 (1984). 

As tissue ages, these initial cross-links decline in quantity as they are converted into other, more complex mature cross-links. These multifunctional cross-links are key to providing strength and stability to tissues. Despite their importance, however, the determined structures are limited (Fig. 6) and other structures may also be present. For some cross-links, such as histidinohydroxylysinonorleucine and pyridinoline, the structures are well defined and the paths to their formation well imderstood (Fig. 6). For others, the information is not as complete. The types and extent of cross-links vary between tissues in a specific manner (50). Finally, in addition to these specific cross-links, as tissue ages it may accumulate a range of additional cross-links that form because of nonenzymatic glycosylation of collagen (51). 

The glycosylation of collagen and basement membrane has been the subject of a series of extensive investigations by M. J. Spiro and Spiro (1971) and R. G. Spiro and Spiro (1971a,b). The galactosyltransferase was purified from a high-speed supernatant (100,000 g) from kidney cortex of 10-day-old rats, and after ammonium sulfate fractionation and gel filtration on Bio-Gel A-1.5m a 12-fold purification had been achieved compared to the 10,000 g supernatant. 

Two reviews containing references to the glycosylation of collagens have appeared one describes the normal metabolism of collagen and comments on the lysylhydroxylase deficiency in the Ehlers-Danlos syndrome type VI, while the other highlights recent developments in studies of articular cartilage collagen. ... 

The many (possibly more than 30) types of collagens found in human connective tissues have substantially the same chemical structure consisting mainly of glycine with smaller amounts of proline and some lysine and alanine. In addition, there are two unusual amino acids, hydroxyproline and hydroxylysine, neither of which has a corresponding base-triplet or codon within the genetic code. There is therefore, extensive post-translational modification of the protein by hydroxylation and also by glycosylation reactions. 

Figure 4. TOP The amount of keto amine-linked glycosylation of insoluble collagen plotted as a function of subject s age. BOTTOM The amount of insoluble collagen plotted as a function of subject s age. Key O. normal +, juvenile-onset diabetic and , maturity-onset diabetic.

John H, Preissner KT, Forssmann WG, Standker L (1999) Novel glycosylated forms of human plasma endostatin and endostatin-related fragments of collagen XV. Biochemistry... 

In collagen, hydroxyproline stabilizes the triple helix structure by forming hydrogen bonds via water between adjacent chains or regions of the same chain. Hydroxylysine provides sites for glycosylation of proteins, and is essential for stabilization of intermolecular cross-links formed by reaction between lysine or hydroxylysine aldehyde and the e-amino group of lysine or hydroxylysine. 

A second posttranslation modification that occurs in the maturation of collagen is the oxygenation of lysine residues to form 5-e/yfAro-hydroxylysine, which serves as an anchor for attachment of carbohydrates in a glycosylation process (equation 2). 

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