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PubMed1996

Clinical performances of galactosyl hydroxylysine, pyridinoline, and deoxypyridinoline in postmenopausal osteoporosis.

We have previously shown that galactosyl hydroxylysine (GHYL), pyridinoline (PYD), and deoxypyridinoline (DPD) have a better accuracy and discriminate power than hydroxyproline in distinguishing postmenopausal osteoporotic women from premenopausal controls. In this study, we evaluated the clinical performances of GHYL, PYD, and DPD, alone or in combination, in distinguishing postmenopausal osteoporotic women (OPBD, n = 26) from age-matched controls (CBD, n = 19). The diagnosis of osteoporosis was based upon the bone density (BD) of the lumbar spine measured by quantitative computed tomography (CBD: BD > 108 mg/cm3; OPBD: BD < 70 mg/cm3). Urinary excretion of GHYL, PYD, and DPD were measured by HPLC, and all data were expressed as the molar ratio with the creatinine excretion (GHYL/CR, PYD/CR, and DPD/CR). The clinical performances were tested by: Z score analysis (Z), Receiver Operated Characteristic curve analysis (%Acc) and logistic-regression analysis of the posterior probabilities for prediction from a logistic model (LOGIST). GHYL/CR, PYD/CR, and DPD/CR were significantly increased in OPBD compared with CBD. The clinical performances were similar for the three assays, with slightly better performances for GHYL/CR (GHYL/CR: Z = 3.14, %Acc = 70 +/- 8, LOGIST P = 0.01; PYD/CR: Z = 2.19, %Acc = 67 +/- 8, LOGIST P = 0.051; DPD/CR: Z = 2.13, %Acc = 65 +/- 8, LOGIST P = 0.06). None of the possible combinations of the three assays yielded better clinical performances than GHYL/CR alone. In conclusion, this study further confirms the validity of GHYL, PYD, and DPD as markers of bone resorption.

Aged↗
PubMed1999

Serum galactosyl hydroxylysine as a biochemical marker of bone resorption.

BACKGROUND: Serum-based biochemical markers of bone resorption may provide better clinical information than urinary markers because direct comparison with serum markers of bone formation is possible and because the within-subject variability of serum markers may be lower. We describe a method for the measurement of free beta-1-galactosyl-O-hydroxylysine (Gal-Hyl) in serum. METHODS: The assay used preliminary ultrafiltration of serum, dansylation, and separation by reversed-phase HPLC with fluorescence detection. Healthy subjects were recruited from population-based studies of bone turnover. RESULTS: The within-run (n = 15) and between-run (n = 15) CVs were 7% and 14%, respectively, at a mean value of 48 nmol/L. In women and pubertal girls, serum free Gal-Hyl correlated with urine free Gal-Hyl (r = 0.84; P <0.001). Serum Gal-Hyl was higher during puberty and increased after menopause. The fractional renal clearance of free Gal-Hyl relative to that of creatinine was 0.90 (95% confidence interval, 0.82-0.98). Serum free Gal-Hyl decreased by 36% (SE = 4%) in 14 patients with mild Paget disease treated with an oral bisphosphonate, and this decrease was significantly (P <0. 001) greater than that seen for either serum tartrate-resistant acid phosphatase (9%; SE = 4%) or serum C-terminal telopeptide of collagen I (19%; SE = 8%). CONCLUSION: Serum free Gal-Hyl may be useful as a serum marker of bone resorption.

Adolescent↗
PubMed2002

Collagen markers deoxypyridinoline and hydroxylysine glycosides: pediatric reference data and use for growth prediction in growth hormone-deficient children.

BACKGROUND: In children and adolescents, markers of bone and collagen metabolism reflect the dynamics of skeletal growth and development. The aim of this study was to assess the relationship of the urinary collagen markers deoxypyridinoline (DPD) and hydroxylysine (Hyl) and its glycosides [galactosyl-Hyl (Gal-Hyl) and glucosyl-Gal-Hyl] with growth. METHODS: Urine samples from 240 apparently healthy children and adolescents (6-19 years; 124 girls) and from 51 prepubertal children with growth hormone (GH) deficiency (3-14 years; 14 girls) were analyzed. Urinary Hyl and its glycosides were quantified by HPLC, and DPD was assessed by chemiluminescence assay. Urinary concentrations of all markers were related to urinary creatinine. RESULTS: Multiple regression analysis revealed that only age and height velocity were independently associated with these markers in healthy children. In GH-deficient patients, the urinary excretion of both analytes after 4 weeks of GH therapy correlated significantly with the height increase during the first treatment year (r = 0.79 for Gal-Hyl; r = 0.70 for DPD; P <0.001 each). In a multivariate linear regression model using Gal-Hyl concentrations at 4 weeks, baseline concentrations of insulin-like growth factor 1 and height velocity after 3 months accounted for 80% of the variability in height gain during the first treatment year. A model using DPD concentrations at 4 weeks, in place of Gal-Hyl concentrations, as well as baseline concentrations of insulin-like growth factor 1 and height velocity after 3 months accounted for 83% of the variability. CONCLUSIONS: These urinary bone and collagen markers give some early indication of growth response, but the prediction of an individual marker is too imprecise to serve as a basis for clinical decisions. Markers of bone and collagen metabolism might be more useful as components of multivariate growth prediction models.

Adolescent↗
PubMed1975

Ehlers-Danlos syndrome in two siblings with deficient lysyl hydroxylase activity in cultured skin fibroblasts but only mild hydroxylysine deficit in skin.

Two siblings suffered from Ehlers-Danlos syndrome characterized by skin fragility, joint laxity and dermal hyperelasticity. The association with microcornea and muscle hypotonia allowed the preliminary classification into type VI according to McKusick. Ultrastructure analysis of skin biopsies revealed poor integration of collagen fibrils into fibres; accordingly, the texture of the connective tissue appeared irregular. Lysyl hydroxylase activity of cultured skin fibroblasts was markedly reduced in the cells of the two patients. Preliminary studies revealed intermediate activity in the cells cultured from the skin of the parents. This finding suggested an autosomal recessive mode of inheritance. Unexpectedly and in contrast to the 3 cases reported in the literature, the hydroxylysine deficit in the patients' skin was, for reasons not yet understood, only mild. Therefore, amino acid analysis of skin is not adequate for the diagnosis of lysyl hydroxylase-deficient Ehlers-Danlos syndrome type VI.

Adolescent↗
PubMed1992

Bone-resorption markers galactosyl hydroxylysine, pyridinium crosslinks, and hydroxyproline compared.

We compared the clinical performances of four bone-resorption (BR) assays (hydroxyproline, HYP; galactosyl hydroxylysine, GHYL; deoxypyridinoline, DPD; and pyridinoline, PYD) in subjects with different BR rates: normal (adult men and premenopausal women), mildly increased (postmenopausal osteoporotic women), high (Paget disease patients), and very high (children). The discrimination power (Z score) and the accuracy (estimated by receiver-operating characteristic analysis) for GHYL, DPD, and PYD were compared with those for HYP. Discrimination power and accuracy were similar for high- and very-high-BR groups for all four assays. However in the mildly increased-BR group, DPD, GHYL, and PYD showed a higher discrimination power and accuracy than did HYP. The clinical performances of HYP, DPD, GHYL, and PYD are comparable for large changes in BR. For modest changes, DPD, GHYL, and PYD are more accurate and have a higher discrimination power than does HYP.

Adult↗
PubMed1990

High predictivity of galactosyl-hydroxylysine in urine as an indicator of bone metastases from breast cancer.

We measured the urinary excretion of galactosyl-hydroxylysine (GH) and hydroxyproline in two groups of women with breast cancer, with (M+, n = 24) and without (Mo, n = 30) clinical, scintigraphic, or radiological evidence of bone metastases. Both these compounds are excreted in larger amounts in the M+ group than in the Mo patients. However, GH, which is a specific marker for bone collagen, provides better predictivity for bone metastases than does hydroxyproline: 92% sensitivity and 90% specificity vs 74% and 79%, respectively, for hydroxyproline.

Adult↗
PubMed1988

Determination of galactosyl hydroxylysine in urine as a means for the identification of osteoporotic women.

A sensitive and specific method is proposed to follow bone collagen degradation. The procedure consists of the measurement of galactosyl hydroxylysine (GH) in urine by HPLC. The aim of the work is to assess the predictive values of the method for the identification of post-menopausal osteoporotic women. By assuming the value of 12 mumol/g creatinine as the threshold value, the sensitivity of the test is 87% and the specificity 60%. Individuals with a GH/creatinine ratio of 12 or below are not likely to be at risk of bone fractures: an equivalent predictive value is provided by the measurement of bone density by quantitative computed tomography. This biochemical method is however simple and not invasive and may be frequently repeated.

Adult↗
PubMed1974

Hydroxylysine-deficient skin collagen in a patient with a form of the Ehlers-Danlos syndrome.

Two sibs with the Ehlers-Danlos syndrome, one of whom was shown to have hydroxylysine-deficient collagen, are described. In addition to the usual features of the Ehlers-Danlos syndrome (loose-jointedness and excessively stretchable, fragile, and bruisable skin), these patients had severe scoliosis and fragility of ocular tissues leading to rupture of the globe or retinal detachment. This combination of symptoms was tentatively classified as Ehlers-Danlos syndrome, Type VI. The condition is inherited as an autosomal recessive. The activity of lysyl hydroxylase was present at a reduced level in fibroblasts cultured from the patient's skin.

Chromosome Aberrations↗
PubMed1976

Parallel studies on collagen hydroxyproline and hydroxylysine in human skin biopsies.

Studies on hydroxyproline and hydroxylysine, the two amino acids characteristic of collagen and related glycoproteins, were undertaken on biopsies of pathologic and clinically normal human skin. No statistically significant differences between clinically normal skin of mamma, thorax, axilla, femur, hip and sacral area were found. A decreased collagen content was seen in chronic pemphigus (bullous pemphigoid), amyloidosis, scleromyxedema and the edge of a leg ulcer. Determination of both amino acids is considered necessary to characterize alterations of collagen.

Adult↗
PubMedDate not supplied

Serum hydroxyproline and hydroxylysine levels in viral hepatitis.

High serum levels of total hydroxyproline (Hyp) and hydroxylysine (Hyl) in patients with acute viral hepatitis were found to be due to a marked increase of the peptide-bound form of these aminoacids. The concentrations of free Hyp and Hyl were only slightly changed. The levels of serum Hyp and Hyl were higher in patients with bilirubin concentration, and decreased during recovery.

Acute Disease↗
PubMed1983

Hereditary nephritis and hypoplastic dysplastic nephropathy: hydroxylysine glycoside excretion and the glomerular basement membrane.

Eleven children aged 5 to 15 years with hereditary nephritis and twelve children with hypoplastic dysplastic nephropathy were studied. The children with hereditary nephritis were divided into 2 groups while correlating the level of renal excretion of hydroxylysine glycosides (HOLG) with ultrastructure of glomerular basement membrane. The first group was characterized by decreased urinary excretion of HOLG and extremely thin basement membranes, the second one - by increased HOLG excretion and thickened membranes, The children with hypoplastic dysplastic nephropathy which were divided into 2 groups according to HOLG excretion differed in presence or absence of anatomic anomalies and in the number of connective tissue dysembryogenetic stigmata. The data are suggestive of an important role and diversity of metabolic derangement of the collagenic component of basement membranes in the pathogenesis of the diseases studied.

Adolescent↗
PubMed1995

Proferrioxamine synthesis in Erwinia amylovora in response to precursor or hydroxylysine feeding: metabolic profiling with liquid chromatography-electrospray mass spectrometry.

Metabolic profiling by capillary liquid chromatography-electrospray mass spectrometry was used to monitor shifts in the proferrioxamine profiles of Erwinia amylovora in response to externally supplied potential proferrioxamine precursors, selected stable-isotope-labeled precursors and atypical precursors. Based on the qualitative and quantitative shifts in the proferrioxamine profiles, lysine and arginine are unambiguous, and agmatine, ornithine, diaminobutyric acid and the corresponding C3-5 diamines are highly likely precursors for proferrioxamine biosynthesis in E. amylovora. 5-Hydroxylysine (Hyl), a recently discovered growth inhibitor for E. amylovora, suppresses proferrioxamine production. The Hyl-induced growth inhibition can be reversed by basic amino acids. The basic amino acids also partly restore proferrioxamine synthesis.

Chromatography, Liquid↗
PubMed1989

Hydroxylysine excretion does not indicate collagen damage with downhill running in young men.

The purpose of this study was to determine whether urinary excretion of hydroxylysine (HO-Lys) is increased following prolonged, predominantly downhill running. Such an increase would be evidence of exercise-induced collagen damage. Each of ten young men performed a treadmill running test to determine VO2peak (an approximation of VO2max) followed by 60 min of intermittent running on -10% slope. Total urine excreted from 48 h pre-exercise to 96h post-exercise was collected in 8-h samples for measurement of HO-Lys. In addition, both urinary 3-methylhistidine (3-MeHis) excretion and serum creatine kinase (SCK) activity were measured as indicators of muscle tissue damage. In no sampling period was post-exercise HO-Lys excretion altered compared with pre-exercise (e.g., pre-exercise: 82.2 +/- 9.6 mumol.24 h-1, mean +/- SE; 51.0 +/- 3.7 mumol.g creatinine-1; post-exercise: 72.9 +/- 2.0 mumol.24 h-1; 47.0 +/- 1.5 mumol.g creatinine-1). SCK activity was increased (346%) 24 h post-exercise, but not immediately, 48 h, or 72 h post-exercise. 3-MeHis excretion was not altered following exercise. There were no strong associations between HO-Lys excretion and either of the markers of muscle damage. We concluded that no evidence of exercise-induced collagen damage was provided by urinary HO-Lys excretion.

Adult↗
PubMed1980

Enzymatic hydrolysis of disaccharide unit of collagen. Isolation of 2-O-alpha-D-glucopyranosyl-O-beta-D-galactopyranosyl-hydroxylysine glucohydrolase from rat spleens.

The hydroxylsine-linked disaccharide unit, 2-O-alpha-D-glucopyranosyl-O-beta-D-galactopyranosyl-hydroxylysine (Glc-Gal-Hyl), prepared from collagens, was hydrolyzed by a glucohydrolase present in rat spleens and lungs. This disaccharide unit was scarcely hydrolyzed by homogenates of intestines, livers, and kidneys, which had a high alpha-D-glucosidase activity for neutral glucosides. The Glc-Gal-Hyl glucohydrolase was purified from rat spleens by affinity chromatography and gel filtration to the extent that sodium dodecyl sulfate/polyacrylamide gel electrophoresis gave a single band stained by Coomassie blue G-250. This purified glucohydrolase had a pH optimum around 5.8, and the Michaelis constant was 5.9 mM when Glc-Gal-Hyl was used as a substrate. This enzyme did not hydrolyze neutral glucosides. It is concluded that this Glc-Gal-Hyl glucohydrolase is responsible for catabolism of the hydroxylsine-linked disaccharide unit derived from collagens in mammals.

Animals↗
PubMed1984

Stimulation by glutamine of the formation of N6-hydroxylysine in a cell-free extract from Aerobacter aerogenes 62-1.

Glutamine may serve as an activator and/or regulator of the N6-hydroxylase (E.C. 1.14.99) of Aerobacter aerogenes 62-1. Activation and stabilization of N6-hydroxylase activity was observed both in vivo and in vitro. Growth in a glutamine-supplemented medium resulted in (1) maximum N6-hydroxylase activity at an earlier stage of growth and (2) higher N6-hydroxylase activity and continued aerobactin synthesis into stationary phase. Storage of P2 in the presence of L-glutamine (1 mM) significantly increased the lifetime of the labile N6-hydroxylase activity. Inclusion of L-glutamine in the incubation mixture typically resulted in a 2-3-fold activation of the hydroxylase activity. The stimulatory effect of glutamine was independent of and additive to the enhancement of N6-hydroxylation by the active component(s) in the supernatant, S2 fraction. Glutamic acid-gamma-semihydrazide activated slightly in the absence of glutamine but activation of the system by glutamine was decreased by this compound. Azaserine was shown to be an uncompetitive inhibitor with respect to lysine and this inhibition was not reversed by glutamine.

Azaserine↗