Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.4.3.13 (lysyl oxidase)
1,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aromatic amine dehydrogenase (AADH) is the second enzyme known to possess the tryptophan tryptophylquinone (TTQ) prosthetic group. Its ability to catalyze the oxidative deamination of a wide range of aromatic and aliphatic amines has been investigated. Steady-state and transient kinetic studies of the reaction of AADH with a series of p-substituted phenylethylamines were performed to determine structure-reactivity correlations. The Km values correlated strongly with hydrophobic effects. The microscopic rate constant associated with TTQ reduction, k3, correlated with electronic substituent effects, particularly field/inductive effects, in a manner consistent with the formation of a carbanionic reaction intermediate in the reductive half-reaction. Transient kinetic studies were also performed with a series of p-substituted benzylamines, which were not substrates in the steady-state assay, but which did stoichiometrically reduce TTQ. The k3 for the reaction with benzylamines also correlated well with electronic effects. The rate constant associated with the release of the aldehyde product was also determined for the phenylethylamines and appears to be the most rate-limiting step in the overall oxidation-reduction reaction. This rate constant correlated with hydrophobic amines. This substrate specificity for aliphatic amines is opposite of that of methylamine dehydrogenase (MADH), the other known TTQ enzyme. On the basis of these studies, a reaction mechanism is proposed for AADH. These data are discussed in relation to the results of structure-reactivity correlation studies of the reactions catalyzed by MADH and two eukaryotic quinoproteins with different quinone prosthetic groups, plasma amine oxidase and lysyl oxidase.
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PMID:Mechanistic studies of aromatic amine dehydrogenase, a tryptophan tryptophylquinone enzyme. 782 40

Lysyl oxidase oxidizes peptidyl lysine in collagen and elastin substrates to residues of alpha-aminoadipic-delta-semialdehyde. The peptidyl aldehydes can then undergo spontaneous condensations with unreacted epsilon-amino groups and with neighboring aldehyde functions, thus forming the covalent crosslinkages which convert elastin and collagen into insoluble fibers. The unique role of lysyl oxidase in the post-translational modification of these proteins qualifies this enzymatic reaction as a potentially pivotal site of biological and/or chemotherapeutic control of collagen fiber deposition. Recent advances in the study of the catalytic mechanism, in the development of active site inhibitors, and in the biosynthesis and regulation of this unusual catalyst are reviewed as are studies on the response of lysyl oxidase in fibrotic liver.
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PMID:Lysyl oxidase: mechanism, regulation and relationship to liver fibrosis. 789 40

Lysyl oxidase (EC 1.4.3.13), a copper-dependent enzyme which catalyses the formation of aldehyde cross-links, and acts primarily on collagen and elastin, is known to be increased during wound healing and in fibrotic disorders including liver cirrhosis and atherosclerosis, and to be decreased in some hereditary connective tissue diseases and in malignant cell lines. A recent study showed that lysyl oxidase might possess tumour suppressor activity as an antioncogene for ras. Little is known about the localization of this enzyme in human skin. In this study, we determined immunohistochemically the localization of lysyl oxidase in normal skin of young and elderly subjects obtained from sun-exposed and unexposed regions of the body. All skin samples tested had similar distributions of lysyl oxidase. The enzyme was present both extracellularly and intracellularly. Extracellularly, a few granular aggregates of immunoreactants were observed along collagen and elastic fibres. These granules were more common in the adventitial portion of the dermis than in the reticular portion. Of all sun-exposed and unexposed regions studied, the skin of the face displayed the greatest amount of extracellular immunoreactants. Immunopositive granules were observed intracellularly in fibroblasts, vascular endothelial cells, sweat glands, sebaceous glands, arrector pili muscles and some keratinocytes. These findings provide evidence that, as suggested in recent reports, lysyl oxidase may have a variety of intracellular functions.
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PMID:Immunohistochemical localization of lysyl oxidase in normal human skin. 791 5

The structural specificity of amine oxidation by lysyl oxidase was investigated using kinetic and NMR spectroscopic analyses. Substrate efficiency increased with increasing molecular distance from the alpha-carbon of the aromatic moiety substituted on the aliphatic chains of a series of primary amines. The p-hydroxyl substituent of p-hydroxybenzylamine significantly increased kcat over that of benzylamine, whereas this was not the case when tyramine and phenethylamine were compared. Direct spectrophotometric measurement of p-hydroxybenzaldehyde formation yielded burst kinetics, the second, slower phase of which was eliminated under anaerobic conditions. Thus, enzyme reoxidation is the more rate-limiting of the two half-reactions catalyzed with this substrate by this ping-pong enzyme. 1H NMR spectroscopy of the alcohol reductively derived from the aldehyde product of the lysyl oxidase-catalyzed oxidation of deuterated tyramine indicated that the pro-S but not the pro-R alpha-deuteron was catalytically abstracted. Moreover, lysyl oxidase catalyzed solvent exchange of protons at the C-2 position. Such stereospecificity and proton exchange uniquely differentiates lysyl oxidase from all but an aortic semicarbazide-sensitive amine oxidase among the pro-S-specific copper-dependent amine oxidases analyzed thus far.
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PMID:Kinetics and stereospecificity of the lysyl oxidase reaction. 809 54

Lysyl oxidase initiates cross-linkage of collagen and elastin by catalysing the formation of a lysine-derived aldehyde. In order to study cross-linking in scleroderma, we used monoclonal antibodies to lysyl oxidase to determine the localization of this enzyme in systemic and localized scleroderma, and compared the distributions obtained with that in normal skin. Using an indirect immunofluorescent antibody method and an avidin-biotinylated enzyme complex method, 11 cases of diffuse type of systemic scleroderma and seven cases of localized scleroderma were studied. In the oedematous stage of systemic scleroderma, intracellular and extracellular lysyl oxidase were remarkably increased in the dermis, particularly in groups around blood vessels. In the sclerotic stage of systemic scleroderma, lysyl oxidase was detected intracellularly in fibroblasts and extracellularly among collagen bundles between the lower dermis and the subcutaneous fat tissue. In localized scleroderma, a marked increase in lysyl oxidase was observed in mononuclear cells and fibroblasts near blood vessels in the lower dermis and in the subcutaneous fat tissue, in addition to the extracellular deposits between collagen bundles. The increase in lysyl oxidase in localized scleroderma was much more common than in the oedematous stage of systemic scleroderma. These findings indicated that intracellular and extracellular expression of lysyl oxidase expression was greater in sclerodermatous skin than in normal skin.
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PMID:Increased expression of lysyl oxidase in skin with scleroderma. 855 21

The known cross-links of bone collagen are derived from lysine and hydroxylysine. The first step in the enzymatic cross-linking process is a deamination by lysyl oxidase producing an aldehyde which then may condense with a lysyl or hydroxylysyl residue of a neighbouring collagen molecule. Some of the resulting divalent aldimine and oxo-imine cross-links may later on be incorporated in trivalent hydroxylysyl-pyridinoline and lysyl-pyridinoline cross-links. In bone collagen prepared from the cancellous bone of vertebral bodies of osteoporotic individuals we found a reduced stability towards acetic acid and pepsin, and a substantial reduction in the concentration of the divalent collagen cross-links compared with sex- and age-matched controls. To what extent do the collagen cross-links influence the mechanical properties of bone? beta-amino-propionitrile (BAPN) irreversibly inhibits the enzyme lysyl oxidase and therefore, the formation of cross-links between the collagen molecules. In the present study female rats, 70 days old, injected subcutaneously two times daily with BAPN (333 mg/kg/day) for 1 month and saline injected control rats were studied. The concentration of the hydroxypyridinium cross-links of femoral mid-diaphyseal cortical bone was determined by HPLC with fluorescence detection and the mechanical properties of the rat femoral diaphyses were analyzed by a materials testing machine. The BAPN injections resulted in a 45% reduction in the concentration of the hydroxypyridinium cross-links and a 31% decrease in the stability of the bone collagen towards acetic acid and pepsin compared with the control rats. No changes were found in ash or collagen concentrations of the cortical bone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced concentrations of collagen cross-links are associated with reduced strength of bone. 857 39

The typical wound healing process after tooth extraction includes several important biological reactions. The collagen fiber, which is the main organic component of connective tissue, plays an important role in the formation of granulation tissue and also bone tissue. Maturation of collagen is controlled by the intermolecular crosslinks in the collagen fibers. Lysyl oxidase, which catalyzes the corresponding aldehyde formation from certain lysyl and hydroxylysyl residues in collagen and elastin in the first step of the linking reaction, is the only known enzyme required in the crosslinking process. This study was designed to analyze changes in the lysyl oxidase activity and calcium content during the healing of rabbit tooth extraction wounds and to survey the relationship between them. Healing tissue in the extraction sockets was removed 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, and 56 days postoperatively. After decalcification, lysyl oxidase was extracted from wound tissue, and activity of this enzyme was examined by tritium-release assay. Radiographs and histologic sections were also obtained in each group. The results show that lysyl oxidase activity can be detected on the first day postoperatively and that it increases sharply from days five to seven, reaching the peak value on the seventh day. After that, enzyme activity decreases gradually and returns to normal range on day 14. Histologically, the healing sockets were filled mainly with young fibrous connective tissue at day seven; osteoid tissue could be found on the lateral wall and fundus of the extraction sockets at the same time. Accompanying the formation of new bone, calcium content increased conspicuously from day 7 to day 14. These results indicate that lysyl oxidase predominantly acts to promote cross-linking of the abundantly synthesized collagen in the early stage of healing of rabbit tooth extraction wounds. When minerals were precipitated at a great rate in the newly-formed bone, lysyl oxidase activity was concurrently decreased.
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PMID:Changes in lysyl oxidase activity and calcium content during the healing of tooth extraction wounds. 926 Apr 63

Lysyl oxidase (EC 1.4.3.13) oxidizes peptidyl lysine to peptidyl aldehyde residues within collagen and elastin, thus initiating formation of the covalent cross-linkages that insolubilize these extracellular proteins. Recent findings raise the possibility that this enzyme may also function intracellularly. The present study provides evidence by immunocytochemical confocal microscopy, Western blot analysis, enzyme assays, and chemical analyses for lysyl oxidase reaction products that this enzyme is present and active within rat vascular smooth muscle cell nuclei. Confocal microscopy indicates its presence within nuclei of 3T3 fibroblasts, as well.
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PMID:Localization and activity of lysyl oxidase within nuclei of fibrogenic cells. 937 58

We characterized a model compound for the lysine tyrosylquinone (LTQ) cofactor of lysyl oxidase which is one of the mammalian copper-dependent amine oxidases. The model compound, 4-butylamino-5-methyl-o-quinone, was prepared from n-butylamine and 4-methylcatechol by the oxidation with sodium iodate and characterized by spectroscopic analyses. The absorption maximum at 494 nm is consistent with that of lysyl oxidase. The model compound was capable of deaminating benzylamine to benzaldehyde at 37 degrees C in buffered aqueous acetonitrile. The aldehyde production was markedly elevated in the presence of the Cu(II)-EDTA complex but inhibited by free Cu(II). The catalytic cycle was observed at pH 10 in the presence of Cu(II), and the pH activity profile showed a broad optimum at about pH 9.0. In the presence of beta-aminopropionitrile and upon deoxygenation with N2 aldelyde, production was decreased. The important features of the reaction were consistent with the enzymatic reaction.
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PMID:Characterization of a model compound for the lysine tyrosylquinone cofactor of lysyl oxidase. 1117 79

The lysyl oxidase- (LO-) mediated insolubilization reactions of the Lys-containing polypeptides have been examined using poly(L-Lys) with degrees of polymerization (Dps) ranging 1 from 2300, copoly(LysxAlay) (x:y = 1:4, 1:3; 1:1, 2:1, and 3:1), copoly(LysxGlyy) (x:y = 1:1 and 2:1), and synthetic adhesive proteins with sequential repetitive units enriched in the Lys residues, poly(Ala-Lys-Pro-Ser-Tyr-Pro-Pro-Thr-Tyr-Lys), poly(Ala-Gly-Tyr-Gly-Gly-Ala-Lys), and poly(Gly-Gly-Gly-Tyr-Gly-Gly-Tyr-Gly-Lys). All of the substrates were insolubilized by the LO-catalyzed oxidation of the epsilon-amino group in the Lys residues. The Dps of the polypeptide substrates did not affect the kinetic constants, the Km and Vmax values. The Km and Vmax values and the insolubilization rates varied depending on the Lys contents in the substrate polypeptides, which were enriched in Gly and Ala residues. As the Lys content increased, the Km and Vmax values became lower and higher, respectively. The insolubilization rates decreased with increase of the Lys content. The time-dependent changes in the LO-catalyzed aldehyde production, the insolubilization, and remaining LO activity demonstrated that the cross-linking and the insolubilization steps occurred along with LO deactivation, indicating that the enzymatic and chemical processes in the LO-mediated insolubilization occur in order.
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PMID:Lysyl oxidase-catalyzed cross-linking and insolubilization reactions of Lys-containing polypeptides and synthetic adhesive proteins. 1171 31


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