Disease relevance of (2S,5R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-1-pyridyl]-5-hydroxy-hexanoic acid

• Differences in spinal bone density between members of a pair were associated with differences in the serum concentrations of parathyroid hormone (P = 0.01) and calcium (P = 0.05) and urinary pyridinoline excretion (P = 0.06), a marker of bone resorption [1].
• Liver collagen cross-linking by pyridinoline, from the lysyl oxidase pathway, and by pentosidine, issued from glycation, was investigated to determine their respective contribution to collagen stabilization in patients with an irreversible liver fibrosis caused by the parasitic granulomatous disease alveolar echinococcosis [2].
• Collagen-type ratios, mature cross-link pyridinoline and total elastin content were similar in both prolapse and control tissues [3].
• Urinary pyridinoline cross-links in Ehlers-Danlos syndrome type VI [4].
• These results demonstrate for the first time the presence of an hydroxypyridinium cross-link in liver fibrosis and suggest that pyridinoline measurement might be an important criterion in assessing the irreversibility of human liver fibrosis [5].

Psychiatry related information on (2S,5R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-1-pyridyl]-5-hydroxy-hexanoic acid

• We recorded menstrual history, physical activity and dietary calcium, and measured serum calcium, phosphate, alkaline phosphatase, osteocalcin, vitamin D, fT3, T4, TSH, PTH, FSH and oestradiol (E2), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion [6].
• METHODS: At baseline, the psychological symptoms with the psychometric scale SCL-90, the bone resorption with the measurement of the urinary levels of pyridinoline and dexoxypirydinoline, and the insulin and lipid metabolism were assessed in 30 postmenopausal women (PMW) and in 18 premenopausal women [7].

High impact information on (2S,5R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-1-pyridyl]-5-hydroxy-hexanoic acid

• In contrast, all four markers of bone resorption, including urinary pyridinoline, deoxypyridinoline, N-telopeptide and hydroxyproline were unchanged with rhIGF-I administration [8].
• Bone turnover was assessed by bone histomorphometry and by measuring serum osteocalcin, a marker of bone formation, and the urinary excretion of pyridinoline cross-links, a marker of bone resorption [9].
• MAIN OUTCOME MEASURES: Skeletal turnover indices including hydroxyproline, deoxypyridinoline, pyridinoline, tartrate-resistant acid phosphatase, alkaline phosphatase, bone Gla protein, and insulin-like growth factor-1 [10].
• Pyridinoline content was increased in fibrotic livers, with the highest values found in patients with alveolar echinococcosis (up to 1.33 pmol/pmol of collagen) [5].
• Analyses of the cell layers revealed that TNF-alpha diminished the levels of mature collagen cross-links, pyridinoline and deoxypyridinoline [11].

Chemical compound and disease context of (2S,5R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-1-pyridyl]-5-hydroxy-hexanoic acid

• Furthermore, there were no significant increments in any bone resorption indicators, including serum tartrate-resistant acid phosphatase and cross-linked carboxy-terminal telopeptide of type I collagen, as well as urine hydroxyproline and pyridinoline [12].
• Markers of bone resorption were fasting urinary calcium, hydroxyproline, pyridinoline, and deoxypyridinoline, all corrected for urinary creatinine [13].
• Clinical performances of galactosyl hydroxylysine, pyridinoline, and deoxypyridinoline in postmenopausal osteoporosis [14].
• In all patients, we performed a baseline bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, serum lipids (total low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol and triglycerides) and serum markers of bone resorption (pyridinoline crosslinks) [15].
• We conclude that the marker of soft-tissue collagen formation, P3NP, is a good marker for overall ponderal and linear growth in preterm infants, whereas the markers of collagen breakdown, Pyd and Dpd, have inverse relationships with weight gain [16].

Biological context of (2S,5R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-1-pyridyl]-5-hydroxy-hexanoic acid

• The increase in pyridinoline cross-links is likely to be the result of increased activity of the enzyme responsible for the hydroxylation of the telopeptides (telopeptide lysyl hydroxylase, or TLH) [17].
• By analyzing the genetic defect of Bruck syndrome, which is characterized by a pyridinoline deficiency in bone collagen, we found two missense mutations in exon 17 of PLOD2, thereby identifying PLOD2 as a putative TLH gene [17].
• After menopause, free deoxypyridinoline (free D-Pyr) excretion measured by HPLC without urine hydrolysis and expressed as a fraction of the total excretion was lower than in premenopausal women (45 +/- 15% vs. 59 +/- 12%, p < 0.005), whereas the fraction of free Pyr was not changed [18].
• The Dpd antibody exhibited less than 1% cross-reaction with free pyridinoline and was shown to react only with free Dpd in urine, having no significant interaction with peptide forms of the crosslinks [19].
• Predominantly type II collagen was present in the alginate bead, as reflected by the unique extent of lysyl hydroxylation, glycosylation, and pyridinoline crosslink formation measured [20].

Anatomical context of (2S,5R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-1-pyridyl]-5-hydroxy-hexanoic acid

• Bone and joint disorders do not affect the pyridinoline content in articular cartilage, but they do not affect the pentosidine content [21].
• However, PTHrP antibody significantly inhibited SCW-induced joint destruction, as measured by its ability to block increases in serum pyridinoline (a marker of cartilage and bone destruction), erosion of articular cartilage, decreases in femoral bone mineral density, and increases in the numbers of osteoclasts in eroded bone [22].
• The bone samples produced high levels of pyridinoline and as much cytokine as synovium pieces obtained from the same joint [23].
• The primary end points were the change between baseline and week 4 in the tender joint count, erythrocyte sedimentation rate, and urinary excretion of pyridinoline [24].
• Peptides containing fluorescent pyridinoline cross-links and Ehrlich's-reactive pyrrole cross-links were isolated from a bacterial collagenase digest of demineralized bone matrix [25].

Associations of (2S,5R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-1-pyridyl]-5-hydroxy-hexanoic acid with other chemical compounds

• In estrogen-replete groups, osteocalcin increased by week 2 of PTH infusion but pyridinoline did not increase until week 4 [26].
• Moreover, patients with PIIINP and bilirubin above normal levels had higher PICP, PINP, ICTP PYR, DPYR, CTX, and NTX [27].
• Values obtained in the ELISA and in pyridinoline by high pressure liquid chromatography were correlated after a correction for creatinine [28].
• Galactosylpyridinoline was also partially converted into free pyridinoline by prolonged alkali hydrolysis [29].
• Urine was assayed for calcium, hydroxyproline, oestrone glucuronide and the collagen cross-links pyridinoline and deoxypyridinoline using high-performance liquid chromatography [30].

Gene context of (2S,5R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-1-pyridyl]-5-hydroxy-hexanoic acid

• Levels of Ag KS, D-pyridinoline (D-Pyr), pyridinoline (Pyr), OSM, TNFalpha, and IL-6 were measured by enzyme-linked immunosorbent assay [31].
• Association between AAAG repeat polymorphism in the P3 promoter of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene and adult height, urinary pyridinoline excretion, and promoter activity [32].
• Combined treatment with IL-1ra and TNFbp decreased urinary pyridinoline cross-links, a marker of bone resorption that reflects osteoclast number and osteoclast activity, whereas treatment with either inhibitor alone was less effective [33].
• Increased formation of pyridinoline cross-links due to higher telopeptide lysyl hydroxylase levels is a general fibrotic phenomenon [34].
• There was no significant change in VEGF, bFGF, pyridinoline, and deoxypyridinoline crosslinks with BAY 12-9566 administration [35].

Analytical, diagnostic and therapeutic context of (2S,5R)-2-amino-6-[4-[(2S)-2-amino-2-carboxy-ethyl]-5-[(3S)-3-amino-3-carboxy-propyl]-3-hydroxy-1-pyridyl]-5-hydroxy-hexanoic acid

• Cross-linked type I collagen was localized by immunohistochemistry with an antibody against the C-terminal part of the molecule, involved in pyridinoline formation, that was measured in serum by radioimmunoassay [2].
• Urinary markers of bone resorption, pyridinoline and deoxypyridinoline were measured before and at 4 weeks after radiotherapy for metastatic bone pain [36].
• Ion-paired, reverse-phase high-performance liquid chromatography (HPLC) was used to measure total urinary excretion of pyridinoline (h-PYD) and deoxypyridinoline (h-DPD) [37].
• On a molar basis, ELISA measures of crosslink-related epitopes were highly correlated with both total and free PYD and DPD as determined by HPLC (r > 0.82, p < 0.001) [38].
• Immunoassay of pyridinoline crosslink excretion in normal adults and in Paget's disease [39].

References