Disease relevance of HYDROXYLYSINE

• Skin fibroblasts from two siblings with hydroxylysine-deficient collagen collagen (Ehlers-Danlos syndrome, type VI) contained normal levels of collagen prolyl hydroxylase activity but were markedly deficient in collagen lysyl hydroxylase activity [1].
• METHODS: We investigated the effect of 3 agents that in earlier studies were found to inhibit KATP channels--NG-nitro-L-arginine, hydroxylysine, and glyburide--on the cerebral arteriolar constriction caused by graded hypocapnia induced by hyperventilation in anesthetized cats equipped with cranial windows [2].
• Serum galactosyl hydroxylysine as a biochemical marker of bone resorption [3].
• Fibrosis of skin is characterized by an increase in pyridinolines, which are hydroxylysine aldehyde derived cross-links usually absent in healthy skin [4].
• Patients with hydroxylysine-deficient collagen disease (Ehlers-Danlos type VI) have diminished lysyl hydroxylase activity [5].

High impact information on HYDROXYLYSINE

• The inhibitor of alpha1-induced platelet aggregation, glucosylgalactosyl hydroxylysine, inhibited the alpha1 binding [6].
• Abnormal properties of collagen lysyl hydroxylase from skin fibroblasts of siblings with hydroxylysine-deficient collagen [1].
• SDS/PAGE analysis demonstrated increased mobilities of the type IV collagen chains, consistent with the absence of hydroxylysine residues and carbohydrates linked to them [7].
• Lysyl hydroxylase (EC 1.14.11.4), a homodimer, catalyzes the formation of hydroxylysine in collagens [8].
• Thus, this work shows that smooth muscle cells have the capacity to phosphorylate hydroxylysine residues in their cell-associated collagens and provides preliminary evidence that a protein kinase is involved [9].

Chemical compound and disease context of HYDROXYLYSINE

• The studies offer a potential means for therapeutic intervention of excessive collagen deposition during fibrosis, using minoxidil or preferably its hydroxy derivatives to limit the supply of hydroxylysine for collagen crosslink formation [10].
• These results suggest that the study of urinary hydroxyproline and hydroxylysine excretion may yield useful information on the metabolism of hepatic collagen in chronic liver disease [11].
• The levels of Hyp, Hyl and Pro were elevated in patients with localized morphoea plaques as compared to the controls indicating major changes of the collagen metabolism in this type of localized scleroderma [12].
• In nephrotoxic serum nephritis, the relative amounts of hydroxyproline, glycine and half-cystine were decreased, whereas the relative amounts of aspartic acid, alanine, lysine and hydroxylysine were increased [13].
• Galactosyl hydroxylysine and deoxypyridinoline are at present the most promising markers of bone resorption [14].

Biological context of HYDROXYLYSINE

• Lysyl hydroxylase is an enzyme that catalyzes the formation of hydroxylysine in collagens and other proteins with collagen-like amino acid sequences [15].
• Phosphorylation of hydroxylysine residues in collagen synthesized by cultured aortic smooth muscle cells [9].
• All of these hydroxylysine residues which occupy a Y position in a Gly-X-Y triplet are possible glycosylation sites since no phenylthiohydantoin amino acid was identified in automated Edman degradation cycles corresponding to these sites [16].
• The data thus indicate that regulation of the extents of lysine hydroxylation and hydroxylysine glycosylation may play a major role in the regulation of collagen fibril formation and the morphology of the fibrils [17].
• Characterization of the components released by alkaline hydrolysis indicated that O-glycosylated hydroxylysine residues are nonenzymatically N-glycated to the same extent as those without an enzymatically attached carbohydrate unit [18].

Anatomical context of HYDROXYLYSINE

• Type II collagen synthesized by cartilage cells contains more hydroxylysine than type I collagen synthesized by tendon and cornea cells [19].
• The localization of collagen hydroxylysine galactosyl- and galactosyl-hydroxylysine glucosyltransferases in purified chick embryo bone microsomes was studied by differential solubilization with nonionic detergents [20].
• Isolation from glomerular basement membrane of a glycopeptide containing both asparagine-linked and hydroxylysine-linked carbohydrate units [21].
• Studies on the catabolism of the hydroxylysine-linked disaccharide units of basement membranes and collagens. Isolation and characterization of a rat kidney alpha-glucosidase of high specificity [22].
• The hydroxylysine/100 hydroxyproline ratios in the phosphoprotein-collagen complexes are much higher than those in dentin or bone collagens [23].

Associations of HYDROXYLYSINE with other chemical compounds

• Identification of S-hydroxylysyl-methionine as the covalent cross-link of the noncollagenous (NC1) hexamer of the alpha1alpha1alpha2 collagen IV network: a role for the post-translational modification of lysine 211 to hydroxylysine 211 in hexamer assembly [24].
• Identification of the post-translational modifications of the core-specific lectin. The core-specific lectin contains hydroxyproline, hydroxylysine, and glucosylgalactosylhydroxylysine residues [25].
• Amino acid analysis of rColXVII-A and -C demonstrated prolyl and lysyl hydroxylation with ratios for hydroxyproline/proline of 0.4 and for hydroxylysine/lysine of 0 [26].
• On the other hand, the relative hydroxylysine content of preparations of the pooled larger helical peptides obtained by cyanogen bromide digestion of normal and hypertrophic tendons was essentially identical [27].
• In diabetic nephropathy, the glomerular basement membrane shows a decreased content of cystine, but hydroxylysine concentrations was only slightly higher than in normal material [28].

Gene context of HYDROXYLYSINE

• Lysyl oxidase (EC 1.4.3.13) initiates the crosslinking of collagens and elastin by catalyzing oxidative deamination of the epsilon-amino group in certain lysine and hydroxylysine residues [29].
• Our results suggest that manipulation of the gene for LH3 can be used to selectively alter the glycosylation and hydroxylation reactions, and provides a new tool to clarify the functions of the unique hydroxylysine linked carbohydrates in collagens and other proteins [30].
• Lysyl hydroxylase (EC 1.14.11.4), an alpha 2 dimer, catalyzes the formation of hydroxylysine in collagens by the hydroxylation of lysine residues in X-Lys-Gly sequences [31].
• Lysyl oxidase (EC 1.4.3.13), an extracellular copper enzyme, initiates the crosslinking of collagens and elastin by catalyzing oxidative deamination of the epsilon-amino group in certain lysine and hydroxylysine residues [32].
• Significantly more hydroxylysine and desmosine were released by AM that had internalized NE than by AM or by culture medium alone [33].

Analytical, diagnostic and therapeutic context of HYDROXYLYSINE

• Hydroxylysine was identified in an acid hydrolysate of somatostatin-28 by gas chromatography/mass spectrometry [34].
• Correlations were significantly improved when a degree of theoretical hydroxylysine glycosylation was applied, showing for the first time that this type of glycosylation influences the negative-staining pattern of collagen fibrils [35].
• Improved HPLC determination of urinary hydroxylysine glycosides to study turnover rate of bone in humans and rats [36].
• Longstanding membranes contained substantial amounts of hydroxyproline, glycine, and hydroxylysine, were capable of digestion by collagenase but not by plasmin, yielded faint positive results with anti-human fibrinogen, and showed fibrils characteristic of collagen by electron microscopy [37].
• Ovariectomy in the rat induces a rapid increase in the urinary excretion of hydroxylysine glycosides and non-reducible crosslink residues [38].

References