Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hydroxylysine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed2005

Interleukin 4 and prolonged hypoxia induce a higher gene expression of lysyl hydroxylase 2 and an altered cross-link pattern: important pathogenetic steps in early and late stage of systemic scleroderma?

The major pathological processes of systemic scleroderma (SSc) comprise inflammation and microvascular damage in the early or acute progressive stage as well as tissue fibrosis and hypoxia in the chronic end stage. Fibrosis seems to be a general phenomenon characterized by an increase of hydroxylysine aldehyde derived collagen cross-links which has been shown in vitro for systemic scleroderma fibroblasts. In the present study, we analyzed the cross-link pattern and the gene expression of lysyl hydroxylase 2 (LH2) in the skin of SSc. Furthermore, we determined the modulatory impact of inflammatory cytokines (interleukin 4, TNF- alphaand interleukin 1alpha/beta) and prolonged hypoxia on the cross-link profile and the gene expression of LH2, respectively. The concentration of hydroxylysine aldehyde derived cross-links was significantly increased in SSc, while the level of lysine aldehyde derived cross-links was not changed. Accordingly, a marked increase of the transcriptional level of LH2 was found. In long term dermal fibroblast cultures, only interleukin 4 induced an increase of hydroxylysine aldehyde derived cross-links accompanied by a higher gene expression of LH2. Furthermore, prolonged hypoxia induced a marked increase of the mRNA level of LH2 in relation to collagen I. The skin of SSc is characterized by an increase of the transcriptional activity of LH2 leading to an altered cross-link pattern. The changes in the quality of the collagenous matrix can also be obtained in cell culture by the exposure of fibroblasts to interleukin 4 or prolonged hypoxia emphasizing the role of this mediator in the acute and the low oxygen tension in the chronic phase of the disease.

Cell Hypoxia↗
PubMed1984

Bovine conglutinin is a collagen-like protein.

Conglutinin is a bovine plasma protein which is relatively large and asymmetric with elevated contents of glycine and, to some extent, proline. Although its physiologic function is unknown, conglutinin is known to bind, in the presence of calcium, to yeast cell walls and to the solid-phase-inactivated third component of complement. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, isolated conglutinin appeared to consist of a single polypeptide chain (Mr 48 000). Unreduced conglutinin consisted of a single stained band with an apparent molecular weight of approximately 300 000. Cross-linking experiments with glutaraldehyde and dimethyl suberimidate suggested that this Mr 300 000 molecule consists of six of the disulfide-linked polypeptide chains. Amino acid composition revealed hydroxylysine and hydroxyproline together with elevated glycine and proline contents. Digestion of reduced, alkylated conglutinin with bacterial collagenase resulted in formation of a precipitate which consisted of an Mr 24 000 peptide which was digested to Mr 21 000 with large quantities of collagenase. These peptides contained less glycine, proline, hydroxylysine, and hydroxyproline than did the intact protein. The supernatant from this digestion mixture was, however, enriched in these four amino acids, with glycine making up nearly one-third of the total. Prolonged digestion with pepsin at 37 degrees C resulted in an Mr 20 000 peptide which was enriched in glycine, proline, hydroxyproline, and hydroxylysine. Amino-terminal sequence analysis showed that the glycine-X-Y repeating sequence begins at residue 26.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed2005

A novel conotoxin from Conus delessertii with posttranslationally modified lysine residues.

A major peptide, de13a from the crude venom of Conus delessertii collected in the Yucatan Channel, Mexico, was purified. The peptide had a high content of posttranslationally modified amino acids, including 6-bromotryptophan and a nonstandard amino acid that proved to be 5-hydroxylysine. This is the first report of 5-hydroxylysine residues in conotoxins. The sequence analysis, together with cDNA cloning and a mass determination (monoisotopic mass of 3486.76 Da), established that the mature toxin has the sequence DCOTSCOTTCANGWECCKGYOCVNKACSGCTH, where O is 4-hydroxyproline, W 6-bromotryptophan, and K 5-hydroxylysine, the asterisk represents the amidated C-terminus, and the calculated monoisotopic mass is 3487.09 Da. The eight Cys residues are arranged in a pattern (C-C-C-CC-C-C-C) not described previously in conotoxins. This arrangement, for which we propose the designation of framework #13 or XIII, differs from the ones (C-C-CC-CC-C-C and C-C-C-C-CC-C-C) present in other conotoxins which also contain eight Cys residues. This peptide thus defines a novel class of conotoxins, with a new posttranslational modification not previously found in other Conus peptide families.

Amino Acid Sequence↗
PubMed1978

The covalent structure of cartilage collagen. Amino acid sequence of residues 552-661 of bovine alpha1(II) chains.

The covalent structure of the first 111 residues from the N-terminus of peptide alpha1(II)-CB10 from bovine nasal-cartilage collagen is presented. This region comprises residues 552-661 of the alpha1(II) chain. The sequence was determined by automated Edman degradation of peptide alpha1(II)-CB10 and of peptides produced by cleavage with trypsin and hydroxylamine. Comparison of this region of the alpha1(II) chain with the homologous segment of the alpha1(I) chain indicated a homology level of 85%, slightly higher than that of 81% reported for the N-terminal region of the alpha1(II) chain (Butler, Miller & Finch (1976) Biochemistry15, 3000-3006). The occurrence of two residues of glycosylated hydroxylysine was established at positions 564 and 603, the first present exclusively as galactosylhydroxylysine and the latter as a mixture of galactosylhydroxylysine and glucosylgalactosylhydroxylysine. Also, two residues at positions 648 and 657 were tentatively identified as glycosylated hydroxylysines. The amino acid sequences adjacent to the hydroxylysine residues so far identified in the alpha1(II) chain were compared with the homologous regions of the alpha1(I) and alpha2 chains, but no obvious prerequisite for hydroxylation could be seen. From comparison with the homologous sequence of the alpha1(I) chain, it appears that the alpha1(II)-chain sequence presented here contains three more amino acids than that reported for the alpha1(I) chain. This triplet would be interposed between residues 63 and 64 of the reported sequence of peptide alpha1(I)-CB7 from calf skin collagen. Data on the purification of the subpeptides and their amino acid compositions have been deposited as Supplementary Publication SUP 50087 (7 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1978) 169, 5.

Amino Acid Sequence↗
PubMed1979

Biochemical alterations of connective tissue metabolism in the arterial walls of stroke-prone spontaneously hypertensive rats.

1. The chemical characteristics of the vascular connective tissue components were determined in stroke-prone (SP), stroke-resistant (SR) spontaneously hypertensive (SH) rats and normotensive Wistar-Kyoto (WK) rats. 2. The ratio of hydroxylysine to hydroxylsine plus lysine in the vascular collagen was increased in 6-month-old SP-SH rats and SR-SH rats as compared with WK rats. 3. An age-related increase in uronic acid and hexose content of the aorta was noted in SP-SH, SR-SH and WK rats. However, the increase was more prominent in SH rats, especially SP-SH rats at the stages examined (11 weeks and over 8 months of age). 4. The ratio of galactosyl-hydroxylysine to glucosyl-galactosyl-hydroxylysine in the aortic collagen was decreased in 6-month-old SH rats, especially SP-SH rats as compared with WK rats. 5. A relative increase in beta and gamma components in aortic collagen was noted in 6-month-old SP-SH rats when compared with SR-SH rats. 6. The increased content of uronic acid and hexose and the structural changes of vascular collagen as demonstrated in SP-SH rats might be related to the fragility of the arterial wall and/or to the pathogenesis of stroke-proneness.

Aging↗
PubMed2004

Premature aggregation of type IV collagen and early lethality in lysyl hydroxylase 3 null mice.

Collagens carry hydroxylysine residues that act as attachment sites for carbohydrate units and are important for the stability of crosslinks but have been regarded as nonessential for vertebrate survival. We generated mice with targeted inactivation of the gene for one of the three lysyl hydroxylase isoenzymes, LH3. The null embryos developed seemingly normally until embryonic day 8.5, but development was then retarded, with death around embryonic day 9.5. Electron microscopy (EM) revealed fragmentation of basement membranes (BMs), and immuno-EM detected type IV collagen within the dilated endoplasmic reticulum and in extracellular aggregates, but the typical BM staining was absent. Amorphous intracellular and extracellular particles were also seen by collagen IV immunofluorescence. SDS/PAGE analysis demonstrated increased mobilities of the type IV collagen chains, consistent with the absence of hydroxylysine residues and carbohydrates linked to them. These results demonstrate that LH3 is indispensable for biosynthesis of type IV collagen and for BM stability during early development and that loss of LH3's functions leads to embryonic lethality. We propose that the premature aggregation of collagen IV is due to the absence of the hydroxylysine-linked carbohydrates, which thus play an essential role in its supramolecular assembly.

Animals↗
PubMed1984

Ehlers-Danlos syndrome type VI: collagen type specificity of defective lysyl hydroxylation in various tissues.

The Ehlers-Danlos syndrome type VI is an inherited disorder of collagen metabolism characterized by a defective lysyl hydroxylase. The resulting lack of hydroxylysine has been found in several connective tissues, all of which show varying degrees of clinical symptoms. In the present study, collagen was isolated from different connective tissues and the degree of hydroxylation of lysyl residues was determined. Subsequently, collagen types I, II, III, IV, and V have been prepared from a number of tissues. Insufficient hydroxylation of lysyl residues was found in type I and type III collagen, whereas types II, IV, and V showed normal amounts of hydroxylysine. The expression of the defect, even for type I and type III collagen, varied widely from one tissue to another. A complete lack of hydroxylysine was observed in skin, while it was less pronounced in tissues such as bone, tendon, lung, or kidney. The data suggest the presence of several isoenzymes having varying affinities to the different collagen types.

Adult↗
PubMed1970

Human glomerular basement membrane: chemical alteration in diabetes mellitus.

The human glomerular basement membrane belongs to the collagen family of proteins. It contains about 7 percent carbohydrate, half of which occurs as glucosylgalactose disaccharide units linked to hydroxylysine. Glomeruli from diabetics contain increased amounts of basement membrane material. In addition, these membranes show a distict chemical alteration c haracterized by a significant decrease in lysine, accoumpanied by an equivalent increase in hydroxylysine and hydroxylysine-linked disaccharide units.

Basement Membrane↗
PubMed1986

Aerobactin biosynthesis and transport genes of plasmid ColV-K30 in Escherichia coli K-12.

The iron-regulated aerobactin operon, about 8 kilobase pairs in size, of the Escherichia coli plasmid ColV-K30 was shown by deletion and subcloning analyses to consist of at least five genes for synthesis (iuc, iron uptake chelate) and transport (iut, iron uptake transport) of the siderophore. The gene order iucABCD iutA was established. The genes were mapped within restriction nuclease fragments of a cloned 16.3-kilobase-pair HindIII fragment. Stepwise deletion and subsequent minicell analysis of the resulting plasmids allowed assignment of four of the five genes to polypeptides of molecular masses 63,000, 33,000 53,000, and 74,000 daltons, respectively. The 74-kilodalton protein, the product of gene iutA, is the outer membrane receptor for ferric aerobactin, whereas the remaining three proteins are involved in biosynthesis of aerobactin. The 33-kilodalton protein, the product of gene iucB, was identified as N epsilon-hydroxylysine:acetyl coenzyme A N epsilon-transacetylase (acetylase) by comparison of enzyme activity in extracts from various deletion mutants. The 53-kilodalton protein, the product of gene iucD, is required for oxygenation of lysine. The 63-kilodalton protein, the product of gene iucA, is assigned to the first step of the aerobactin synthetase reaction. The product of gene iucC, so far unidentified, performs the second and final step in this reaction. This is based on the chemical characterization of two precursor hydroxamic acids (N epsilon-acetyl-N epsilon-hydroxylysine and N alpha-citryl-N epsilon-acetyl-N epsilon-hydroxylysine) isolated from a strain carrying a 0.3-kilobase-pair deletion in the iucC gene. The results support the existence of a biosynthetic pathway in which aerobactin arises by oxygenation of lysine, acetylation of the N epsilon-hydroxy function, and condensation of 2 mol of the resulting aminohydroxamic acid with citric acid.

Acetyltransferases↗
PubMed1976

The effects of Z plasty on hypertrophic scars.

Hypertrophic scar tissue has been observed to soften and thin following Z plasty without removal of any of the scar tissue. Histochemical studies of tissue before and after Z plasty showed that abnormally sulfated mucopolysaccharides were replaced by normal acid mucopolysaccahrides within 14 days. Collagen in hypertrophic scar appeared in nodules and fibers perpendicular to the surface of the skin rather than as long straight fibers parallel to the skin surface as normally seen. Elastic fibers were reduced and scar was relatively avascular. Following Z plasty the amount of collagen decreased and fibers were oriented in bundles at right angles to each other, parallel to the surface. When tissue was examined by electron microscopy collagen fibers showed marked variation in diameter. Microfibrils were increased and there were aggregates of fibrils with periodicity of 1500 to 1600 A. Following Z plasty, areas which previously contained only microfibrils now had unit collagen fibers with normal periodicity. Urinary excretions of hydroxyproline and hydroxylysine, amino acids found only in collagen, were increased following Z plasty, coinciding with the softening of the scar. Excretion of the disaccharide, glucosylgalactosylhydroxylysine, predominantly found in skin, increased following Z plasty, while excretion of the monosaccharide, galactosyl-hydroxylysine, predominant in bone collagen, remained constant. Amino acid composition of collagen, remained constant. Amino acid composition of collagen isolated from hypertrophic scars was similar to that present in skin and tendon, and unlike that in cartilage or infant dermis. Hydroxyproline content was slightly decreased and hydroxylysine content slightly increased compared to skin or tendon. Histochemical, ultrastructural and biochemical studies of the same specimens suggested that collagen with disordered fibril formation was present in the hypertrophic scar and was degraded following Z plasty. Changes in the molecule which occurred after synthesis of the protein core might be responsible both for the failure of normal maturation of the scar and for its sensitivity to degradative enzymes following Z plasty.

Adolescent↗
PubMed1986

"In vitro" fibril formation of type I collagen from different sources: biochemical and morphological aspects.

Acid soluble type I collagen was prepared from foetal and adult bovine tendon and skin and from adult bovine cornea. The degree of hydroxylysine glycosylation and the hydroxylysine di-to monoglycoside ratio as well as the "in vivo" fibril diameters, were shown to be tissue and age-dependent. Fibrils of type I collagens were reconstituted "in vitro" monitoring at 313 nm. The fibrils obtained were examined by electron microscopy. It was shown that the "in vitro" lateral growth of collagen fibrils leads to the formation of fibrils with maximum diameters which may be correlated to those of the corresponding native fibrils. Moreover it is suggested that one of the factors controlling the lateral growth of collagen may be at the level of hydroxylysine glycosylation.

Animals↗
PubMed1999

Influence of site and age on biochemical characteristics of the collagen network of equine articular cartilage.

OBJECTIVE: To determine variations in biochemical characteristics of equine articular cartilage in relation to age and the degree of predisposition for osteochondral disease at a specific site. SAMPLE POPULATION: Articular cartilage specimens from 53 horses 4 to 30 years old. PROCEDURE: Healthy specimens were obtained from 2 locations on the proximal articular surface of the first phalanx that had different disease prevalences (site 1 at the mediodorsal margin and site 2 at the center of the medial cavity). Water, total collagen, and hydroxylysine contents and enzymatic (hydroxylysylpyridinoline [HP]) and nonenzymatic (pentosidine) crosslinking were determined at both sites. Differences between sites were analyzed by ANOVA (factors, site, and age), and age correlation was tested by Pearson's product-moment correlation analysis. Significance was set at P< 0.01. RESULTS: Correlation with age was not found for water, collagen, hydroxylysine contents, and enzymatic cross-linking. Nonenzymatic crosslinking was higher in older horses and was linearly related to age (r = 0.94). Water and collagen contents and HP and pentosidine crosslinks were significantly higher at site 1. Hydroxylysine content was significantly lower at site 1. CONCLUSIONS: Except for nonenzymatic glycation, the composition of articular cartilage collagen does not change significantly in adult horses. A significant topographic variation exists in biochemical characteristics of the articular cartilage collagen network in equine metacarpophalangeal joints. These differences may influence local biomechanical properties and, hence, susceptibility to osteochondral disease, as will greater pentosidine crosslinks in older horses that are likely to cause stiffer and more brittle cartilage.

Aging↗
PubMed1991

The cartilage collagens: structural and metabolic studies.

The molecular sites of crosslinking between types II and IX collagens of bovine articular cartilage have been defined. All 3 chains of the type IX molecule, alpha 1 (IX), alpha 2 (IX) and alpha 3 (IX), contain an hydroxylysine close to the N-terminus of the central COL2 triple helical domain that can crosslink to an hydroxylysine aldehyde in an alpha 1 (II) N-telopeptide. One chain, alpha 3 (IX), also contains a triple helical hydroxylysine farther into COL2 that crosslinks specifically to an alpha 1 (II)C-telopeptide. The metalloprotease, stromelysin, is capable of depolymerizing the type II-type IX complex by bisecting the type IX collagen molecule and cleaving telopeptides from type II collagen. We discuss the significance of these findings in understanding the structure, growth and remodeling of the heterotypic collagen network of articular cartilage.

Animals↗
PubMed1984

Characterization of collagen hydroxylysyl glycosyltransferases as mainly intramembranous microsomal enzymes.

The localization of collagen hydroxylysine galactosyl- and galactosyl-hydroxylysine glucosyltransferases in purified chick embryo bone microsomes was studied by differential solubilization with nonionic detergents. Brij-35 (polyoxyethylene 25-lauryl ether) which selectively releases intracisternal proteins, and Triton X-100, whose specificity varies with its concentration, were used in the presence or absence of high ionic strength NaCl. These methods were used previously to characterize prolyl hydroxylase as intracisternal and lysyl hydroxylase as mainly intramembranous. The distribution of both glycosyltransferases within microsomes was similar to that of lysyl hydroxylase; approximately 70-80% of their activities are intramembranous with the remainder intracisternal. Collagen hydroxylysine glucosyltransferase differed from prolyl and lysyl hydroxylase and the galactosyltransferase in that its activity in vitro was apparently inhibited by membrane vesicles, even in the presence of detergents at concentrations which permeabilize the membrane. Accurate measurement of its activity could be achieved only by its separation from vesicles after detergent treatment. The common location of the major portion of lysyl hydroxylase and the glycosyltransferase activities suggests that they may act as a multienzyme complex to preferentially modify certain lysyl residues in nascent procollagen chains as they traverse the membrane of the endoplasmic reticulum. Since these enzymes do not act on helical collagen, their physical separation from prolyl hydroxylase may ensure that modifications of lysine residues occur prior to formation of hydroxyproline, which stabilizes the helical form.

Animals↗
PubMed1994

Metabolism of polyamines and basic amino acids in Erwinia amylovora: application of liquid chromatography/electrospray mass spectrometry to proferrioxamine precursor feeding and inhibition studies.

Erwinia amylovora, the etiological agent of fire blight, produces a family of proferrioxamine siderophores, which may be essential for the pathogen to establish itself in its hosts. If so, then control of fire blight may perhaps be possible via interference with proferrioxamine biosynthesis. Proof of this hypothesis requires prior knowledge of the corresponding biosynthetic pathways in E. amylovora. As a first step towards understanding proferrioxamine biosynthesis, it was of interest to investigate the ability of the fire blight bacterium to utilize various potential biosynthetic pathways for diamines. Feeding of lysine, ornithine and diaminobutyric acid gave rise to highly elevated levels of cadaverine, putrescine and diaminopropane, respectively, indicating that the corresponding decarboxylase activities are all present in E. amylovora. The conclusion for lysine decarboxylase was confirmed with (15N2)lysine, which was converted to (15N2)cadaverine. Arginine did not increase putrescine levels substantially, but (13C6)arginine nevertheless gave rise to (13C4)putrescine while suppressing excretion of non-labeled putrescine. A serendipitous result of this study was the finding that the growth of E. amylovora can be inhibited with 5-hydroxylysine and 1,4-diamino-2-butanone. The mechanism of inhibition appears complex and is not yet understood. For 5-hydroxylysine, preliminary investigations point to a competitive inhibition of lysine decarboxylase. However, the growth inhibition cannot be reversed by providing cadaverine, the decarboxylation product of lysine.

Amino Acids↗
PubMed1982

Variation of antimetabolite sensitivity with different carbon sources in Bacillus subtilis.

The susceptibility of Bacillus subtilis to amino acid analogues was found to be markedly influenced by the carbon source used in the test media. Thialysine inhibited the bacterium with a greater number of carbon sources than the other two analogues tested. 5-Hydroxylysine was inhibitory with glycerol, lactose, D-xylose, L-arabinose and soluble starch while ethionine showed toxicity with lactose, D-xylose and L-arabinose. None of these analogues were toxic at the levels tested when D-galactose was used as carbon source. The bacterium was not susceptible to thialysine with glycerol, to 5-hydroxylysine with L-arabinose and to ethionine with lactose.

Arabinose↗
PubMed1996

Galactosylhydroxylysine and pyridinium cross links in monitoring the bone response to hormone replacement therapy.

Aim of the study was to compare urinary galactosyl-hydroxylysine (GHyl), deoxypyridinoline (D-Pyr) and pyridinoline (Pyr) before and after 5 to 9 months of hormone replacement therapy (HRT) in postmenopausal women. The urinary markers were measured by HPLC in the second void of fasting samples and were expressed as ratio to creatinine. GHyl was also expressed as a ratio to glucosylgalactolysyl-hydroxylysine (GGHyl). After short-term hormone replacement therapy, urinary D-Pyr fell significantly, but Pyr and GHyl, also when expressed as a ratio to GGHyl, remained unmodified. We conclude that GHyl and Pyr are not useful markers in monitoring the bone response to HRT in postmenopausal women.

Alkaline Phosphatase↗
PubMed1987

Modulation of nitrate uptake in Anacystis nidulans by the balance between ammonium assimilation and CO2 fixation.

Gradual inhibition of ammonium assimilation in Anacystis nidulans cells by increasing concentrations of 5-hydroxylysine resulted in a progressive enhancement of nitrate uptake. For 5-hydroxylysine-treated cells, the magnitude of the inhibition of nitrate uptake promoted by added ammonium was dependent on the ammonium assimilation capacity. In cells with a moderate ammonium assimilation activity, acceleration of CO2 fixation induced by bicarbonate addition antagonized the negative effect of ammonium, allowing full nitrate uptake activity. The results support the contention that nitrate utilization is under the feed-back control exerted by products of its own assimilation via ammonium, the inhibitory effect being potentiated by ammonium addition and alleviated by enhanced CO2 fixation. Results of amino acid analysis in cells exhibiting different capacities to utilize nitrate speak against these compounds as direct effectors of nitrate uptake.

Amino Acids↗