Characterization of urinary degradation products derived from type I collagen. Identification of a beta-isomerized Asp-Gly sequence within the C-terminal telopeptide (alpha1) region.

TY - JOUR

T1 - Characterization of urinary degradation products derived from type I collagen. Identification of a beta-isomerized Asp-Gly sequence within the C-terminal telopeptide (alpha1) region.

AU - Fledelius, C

AU - Johnsen, A H

AU - Cloos, P A

AU - Bonde, M

AU - Qvist, P

N1 - Keywords: Adult; Amino Acid Sequence; Antibodies, Monoclonal; Aspartic Acid; Bone and Bones; Child; Chromatography, High Pressure Liquid; Collagen; Collagen Type I; Enzyme-Linked Immunosorbent Assay; Glycine; Humans; Isomerism; Molecular Sequence Data; Peptides

PY - 1997

Y1 - 1997

N2 - The heterogeneity of urinary degradation products of C-terminal telopeptides derived from the alpha1 chain of human type I collagen was investigated and characterized. The urinary fragments characterized in this study consisted of two cross-linked (X) amino acid sequences derived from the C-terminal telopeptide (alpha1) of type I collagen. Fragments containing the sequence EXAHDGGR, with a DG site being either nonisomerized (Asp-Gly) or beta-isomerized (betaAsp-Gly), were identified. Pyridinoline was detected among the pyridinium cross-links, but there was a dominance of deoxypyridinoline and a cross-link containing pyridinoline having a molecular weight identical with that of galactosyl pyridinoline. A nonfluorescent cross-link was also found. The concentration of fragments derived from the C-terminal telopeptide region of type I collagen containing the sequence Asp-Gly (alphaCTX) and/or betaAsp-Gly (betaCTX) was measured by enzyme-linked immunosorbent assays in urine and in collagenase digests of trabecular and cortical bone of young and old origin. It was shown that the urinary ratio between such fragments, alphaCTX/betaCTX, was higher in children compared with adults and that the ratio decreased with increasing age of bone. The results indicated that the C-terminal telopeptide fragments derived from type I collagen excreted into urine originated mainly from bone. In conclusion, it is demonstrated for the first time that the C-terminal telopeptide alpha1 chain of type I collagen contains an Asp-Gly site prone to undergo beta-isomerization and that the degree of beta-isomerization of this linkage apparently increases with increasing age of bone. These findings indicate that the ratio alphaCTX/betaCTX might be clinically important in diagnosing metabolic bone diseases.

AB - The heterogeneity of urinary degradation products of C-terminal telopeptides derived from the alpha1 chain of human type I collagen was investigated and characterized. The urinary fragments characterized in this study consisted of two cross-linked (X) amino acid sequences derived from the C-terminal telopeptide (alpha1) of type I collagen. Fragments containing the sequence EXAHDGGR, with a DG site being either nonisomerized (Asp-Gly) or beta-isomerized (betaAsp-Gly), were identified. Pyridinoline was detected among the pyridinium cross-links, but there was a dominance of deoxypyridinoline and a cross-link containing pyridinoline having a molecular weight identical with that of galactosyl pyridinoline. A nonfluorescent cross-link was also found. The concentration of fragments derived from the C-terminal telopeptide region of type I collagen containing the sequence Asp-Gly (alphaCTX) and/or betaAsp-Gly (betaCTX) was measured by enzyme-linked immunosorbent assays in urine and in collagenase digests of trabecular and cortical bone of young and old origin. It was shown that the urinary ratio between such fragments, alphaCTX/betaCTX, was higher in children compared with adults and that the ratio decreased with increasing age of bone. The results indicated that the C-terminal telopeptide fragments derived from type I collagen excreted into urine originated mainly from bone. In conclusion, it is demonstrated for the first time that the C-terminal telopeptide alpha1 chain of type I collagen contains an Asp-Gly site prone to undergo beta-isomerization and that the degree of beta-isomerization of this linkage apparently increases with increasing age of bone. These findings indicate that the ratio alphaCTX/betaCTX might be clinically important in diagnosing metabolic bone diseases.

M3 - Journal article

C2 - 9092508

SN - 0021-9258

VL - 272

SP - 9755

EP - 9763

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 15

ER -