Pyridinium cross-links

Figure 49-24 Pyridtnium cross-links and N-telopeptides of type I collagen. Cross-links occur at two intermolecular sites in the collagen fibril (i) two N-telopeptides are linked to a helical site at residue 930, and (2) two C-te opeptides are linked to helical residue 87.The location and amino acid sequence of the N-telopeptide (NTx) and the C-telopeptide (CTx) and the structures of the free pyridinium cross-links (pyridinoline and deoxypyridinoline) are shown.

Intermolecular cross-linking sites have been located that form the pyridinium cross-links in type I collagen (Figure 49-24). Two N-telopeptide sites are linked to the helical site at amino acid 930 (N-telopeptide) or two C-telopeptides are linked to the helical site amino acid 87 (C-telopeptide). 

It does not appear to be absorbed from the diet. Pyridinium cross-links (DPD and PYD) and telopeptides... 

Pyridinium Cross-links (Deoxypyridinoline and Pyridi-noline). DPD and PYD were originally measured by HPLC (see Table 49-5). Today, DPD is measured primarily by immunoassay using automated analyzers (EIA with chemiluminescence detection and ICMA) or manual ELISA. Unlike most HPLC methods, which measure total DPD and total PYD, the immunoassays for DPD or DPD/PYD measure primarily free but not peptide-bound forms. In urine, approximately 40% of the PYD and DPD is free and 60% is protein-bound. 

Body JJ, Delmas PD. Urinary pyridinium cross-links as markers of bone resorption in tumor-associated hypercalcemia. J Clin Endocrinol Metab 1992 74 471-5. 

Jenldns DK, Kung VT. Monoclonal antibody assay for free urinary pyridinium cross-links. Clm Chem 1996 42 1168-75. 

Schlemmer A, Hassager C, Jensen SB, Christiansen C. Marked diurnal variation in urinary excretion of pyridinium cross-links in premenopausal women. J Clin Endocrinol Metab 1992 74 476-80. 

Uebelhart D, Schlemmer A, Johansen JS, Gineyts E, Christiansen C, Dehnas PD. Effect of menopause and hormone replacement therapy on the urinary excretion of pyridinium cross-links. J Clin Endocrinol Metab 1991 72 367-73. 

Pyridinium cross-links (pyridinoline and deoxypyridinoline) Posttranslational modification of lysine and hydroxylysine residues of collagen... 

Hydroxyproline. from the breakdown of collagen, can be used to monitor bone resorption. However, urinary hydroxyproline is markedly inlluenced by dietary gelatin. Better markers of resorption are required. One candidate would seem to be another collagen degradation product the I ragmcnts of the molecule containing the pyridinium cross links. Deoxypyridinolinc is one such crosslink which is specific for bone, and not metabolized or influenced by diet. 

Bonnet, J. 1994. Evaluation and comparison of urinary pyridinium cross-links in two rat models of bone loss—Ovariectomy and adjuvant polyarthritis. Bone and Mineral 26 155-167. 

Egger, C. D., R. C. Miihlbauer, R. Felix, P. D. Delmas, S. C. Marks, and H. Fleisch. 1994. Evaluation of using urinary pyridinium cross-link excretion as a marker of bone resorption in the rat. Journal of Bone and Mineral Research 9 1211-1219. 

---