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Collagen fragments in urine derived from bone resorption are highly racemized and isomerized: a biological clock of protein aging with clinical potential.
Biochem J. 2000 Feb 01; 345 Pt 3:473-80.BJ

Abstract

Fragments of the alpha1 C-terminal telopeptide of type I collagen containing the sequence AHDGGR(1209-1214) (CTx) can be measured in urine as an index of bone resorption. We report here that these molecules undergo racemization and isomerization of Asp(1211) in vitro and in vivo, generating a mixture of four isomers: the native peptide form (alphaL), an isomerized form containing a beta-Asp bond (betaL), a racemized form containing a D-Asp residue (alphaD) and an isomerized/racemized form (betaD). To study these reactions at this specific site in collagen, we have employed four immunoassays, each specific for one of the isoforms, and developed HPLC methods for their separation. The kinetics of these reactions were studied in vitro under physiological conditions by incubation of synthetic AHDGGR hexapeptide or mineralized bone collagen. Reactions were found to be strongly shifted towards the beta-Asp forms and slightly in favour of the D-enantiomeric forms. CTx isomers were measured in human urine and in enzymic digests of bovine bone collagen. The results indicated that the extent of racemization and isomerization were correlated with the age and turnover of collagen. The ratios between the native and age-related forms of CTx were elevated in urine from patients with Paget's disease or osteoporosis as compared with that from healthy adults. The alphaL/alphaD CTx ratio had the highest discriminatory power (T-score=23.2; P<0.0001 and T-score=1. 5; P<0.0001 for Paget's disease and osteoporosis respectively). In conclusion, these findings indicate that an assessment of CTx ratios in urine may provide an estimate of bone turnover, aiding in the diagnosis of metabolic bone diseases.

Authors+Show Affiliations

Osteometer BioTech A/S, Osteopark, Herlev Hovedgade 207, DK-2730 Herlev, Denmark. paul-cloos@osteobio.dkNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10642504

Citation

Cloos, P A., and C Fledelius. "Collagen Fragments in Urine Derived From Bone Resorption Are Highly Racemized and Isomerized: a Biological Clock of Protein Aging With Clinical Potential." The Biochemical Journal, vol. 345 Pt 3, 2000, pp. 473-80.
Cloos PA, Fledelius C. Collagen fragments in urine derived from bone resorption are highly racemized and isomerized: a biological clock of protein aging with clinical potential. Biochem J. 2000;345 Pt 3:473-80.
Cloos, P. A., & Fledelius, C. (2000). Collagen fragments in urine derived from bone resorption are highly racemized and isomerized: a biological clock of protein aging with clinical potential. The Biochemical Journal, 345 Pt 3, 473-80.
Cloos PA, Fledelius C. Collagen Fragments in Urine Derived From Bone Resorption Are Highly Racemized and Isomerized: a Biological Clock of Protein Aging With Clinical Potential. Biochem J. 2000 Feb 1;345 Pt 3:473-80. PubMed PMID: 10642504.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Collagen fragments in urine derived from bone resorption are highly racemized and isomerized: a biological clock of protein aging with clinical potential. AU - Cloos,P A, AU - Fledelius,C, PY - 2000/1/22/pubmed PY - 2000/3/25/medline PY - 2000/1/22/entrez SP - 473 EP - 80 JF - The Biochemical journal JO - Biochem J VL - 345 Pt 3 N2 - Fragments of the alpha1 C-terminal telopeptide of type I collagen containing the sequence AHDGGR(1209-1214) (CTx) can be measured in urine as an index of bone resorption. We report here that these molecules undergo racemization and isomerization of Asp(1211) in vitro and in vivo, generating a mixture of four isomers: the native peptide form (alphaL), an isomerized form containing a beta-Asp bond (betaL), a racemized form containing a D-Asp residue (alphaD) and an isomerized/racemized form (betaD). To study these reactions at this specific site in collagen, we have employed four immunoassays, each specific for one of the isoforms, and developed HPLC methods for their separation. The kinetics of these reactions were studied in vitro under physiological conditions by incubation of synthetic AHDGGR hexapeptide or mineralized bone collagen. Reactions were found to be strongly shifted towards the beta-Asp forms and slightly in favour of the D-enantiomeric forms. CTx isomers were measured in human urine and in enzymic digests of bovine bone collagen. The results indicated that the extent of racemization and isomerization were correlated with the age and turnover of collagen. The ratios between the native and age-related forms of CTx were elevated in urine from patients with Paget's disease or osteoporosis as compared with that from healthy adults. The alphaL/alphaD CTx ratio had the highest discriminatory power (T-score=23.2; P<0.0001 and T-score=1. 5; P<0.0001 for Paget's disease and osteoporosis respectively). In conclusion, these findings indicate that an assessment of CTx ratios in urine may provide an estimate of bone turnover, aiding in the diagnosis of metabolic bone diseases. SN - 0264-6021 UR - https://www.unboundmedicine.com/medline/citation/10642504/Collagen_fragments_in_urine_derived_from_bone_resorption_are_highly_racemized_and_isomerized:_a_biological_clock_of_protein_aging_with_clinical_potential_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/10642504/ DB - PRIME DP - Unbound Medicine ER -