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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)

Lysyl oxidase is a specific amine oxidase that catalyzes the formation of aldehyde cross-link intermediates in collagen and elastin. In this study, lysyl oxidase from embryonic chick cartilage was purified to constant specific activity and a single protein band on sodium dodecyl sulfate acrylamide gel electrophoresis. This band had an apparent molecular weight of 62,000. The eluted protein cross-reacted with inhibiting antisera developed against highly purified lysyl oxidase. The highly purified enzyme was active with both insoluble elastin and embryonic chick skin or bone collagen precipitated as reconstituted, native fibrils. There was low activity with nonhydroxylated collagen, collagen monomers, or native fibrils isolated from lathyritic calvaria. The maximum number of aldehyde intermediates formed per molecule of collagen that became insoluble was two. These results indicate that lysyl oxidase has maximum activity on ordered aggregates of collagen molecules that may be overlapping associations of only a few collagen molecules across. Formation of aldehyde intermediates and cross-links during fibril formation may facilitate the biosynthesis of stable collagen fibrils and contribute to increased fibril tensile strength in vivo.
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PMID:Collagen cross-linking. Purification and substrate specificity of lysyl oxidase. 0 1

It has been reported that bovine aorta amine oxidase oxidizes lysine residues in tropoelastin to allysine (Rucker, R.B. and O'Dell, B.L. (1971) Biochim. Biophys. Acta 235, 32-43). Pure bovine aorta amine oxidase was isolate by DEAE-cellulose, hydroxylapatite, Bio-Gel A-1.5 m and concanavalin A-Sepharose 4B chromatography. Enzymatic, chromatographic and immunochemical tests disclosed that pure bovine aorta amine oxidase was not a lysyl oxidase capable of oxidizing the lysine residues of tropoelastin to allysine; The bovine aorta amine oxidase preparation used by Rucker and O'Dell appears to have been contaminated with lysyl oxidase which is the emzyme that oxidizes some of the lysine residues in tropoelastin and tropocollagen to allysine.
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PMID:A purification procedure for the isolation of homogeneous preparations of bovine aorta amine oxidase and a study of its lysyl oxidase activity. 23 99

Inhibition of lysyl oxidase (protein-lysine 6-oxidase, EC 1.4.3.13) decreases the rate of collagen and elastin cross-link formation and produces osteolathyrism in animals. Organic nitriles, including beta-aminopropionitrile (BAPN), have been shown to irreversibly inhibit lysyl oxidase in vitro. Both BAPN and 3,3'-iminodipropionitrile (IDPN) have been shown to produce osteolathyric changes when administered to animals. To date compounds that have been reported to inhibit this enzyme possess a primary amine functional group. In this study a series of primary and substituted aminopropionitriles was studied for their ability to inhibit lysyl oxidase activity both in vitro and in vivo. Our results show that of the compounds tested, BAPN was the most potent inhibitor of the enzyme. Reversible inhibition of lysyl oxidase in vitro was found with two secondary aminonitriles, IDPN and monomethylaminopropionitrile (MMAPN). There was no inhibition of enzyme activity associated with the tertiary compound 3,3'-dimethylaminopropionitrile (DMAPN) or propionitrile, a compound lacking an amine functional group. IDPN was found to produce a slight irreversible inhibition of the enzyme both in vitro and in vivo. Pretreatment of rats with pargyline, an inhibitor of monoamine oxidase, was found to increase the inhibitory potential of BAPN (p < or = .1). Pargyline pretreatment did not alter the inhibitory potential for any of the other aminonitriles tested. These results suggest that the presence of a primary amino functional group is not a strict requirement for inhibition of lysyl oxidase. In addition, reversible and irreversible mechanisms of inhibition may be involved in the production of osteolathyric changes associated with IDPN exposure.
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PMID:In vitro and in vivo inhibition of lysyl oxidase by aminopropionitriles. 135 58

Quinones and related quinonoid substances catalyze redox cycling at an alkaline pH in the presence of excess glycine as reductant. With nitroblue tetrazolium and oxygen present there is concomitant reduction of the tetrazolium to formazan. This property of quinonoid compounds is used for the specific staining of quinoproteins, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotted onto nitrocellulose. The dopa-containing vitelline proteins and the 6-hydroxydopa-containing bovine serum amine oxidase are stained with the nitroblue tetrazolium/glycinate reagent. Also, the mammalian quinoproteins, diamine oxidase and lysyl oxidase, purported to contain pyrroloquinoline quinone, tested positive in this procedure. No quinonoid components were detected in three putative pyrroloquinoline quinone-containing quinoproteins, dopamine beta-hydroxylase, lipoxygenase, and peptidylglycine-amidating monoxygenase. Redox-cycling staining therefore confirms the presence of covalently bound quinones in the copper-dependent amine oxidases, but not in two putative quinoprotein oxygenases. Clarification of the biological significance of quinolation should be facilitated by identification of quinoproteins using this approach.
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PMID:Specific detection of quinoproteins by redox-cycling staining. 170 37

Recent evidence has revealed that lysyl oxidase, plasma amine oxidase and diamine oxidase each contain copper and pyrroloquinoline quinone at their active sites as cofactors essential to their catalytic functions. It thus seems likely that these enzymes will share similar mechanisms of action. Since mechanism-based inhibitors of lysyl oxidase have important chemotherapeutic potential for the control of fibrotic disease, the relative inhibitory potential of such agents toward catalytically similar amine oxidases was assessed in the present study using purified preparations of lysyl oxidase, diamine oxidase, plasma amine oxidase and the flavin-dependent mitochondrial monoamine oxidase A and B. The results indicate that there is sufficient difference between the sensitivities of lysyl oxidase and the other amine oxidases to beta-aminopropionitrile to warrant its consideration as an antifibrotic agent in vivo, while also revealing that aminoguanidine, clorgyline and deprenyl are sufficiently selective for diamine oxidase, monoamine oxidase A and monoamide oxidase B, respectively, to differentiate between lysyl oxidase and these enzymes at appropriate concentrations.
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PMID:Comparative sensitivities of purified preparations of lysyl oxidase and other amine oxidases to active site-directed enzyme inhibitors. 257 59

Several methods have been used to study the distribution of the semicarbazide-sensitive amine oxidase (SSAO) within the wall of the rat aorta. After separation of the smooth muscle-containing layers of the tunica media from the connective tissue of the tunica adventitia, much higher specific enzyme activity (measured with 1 microM benzylamine) was found in homogenates of the media than of adventitia. Similar results were obtained for MAO-A (with 1 mM 5-HT as substrate). SSAO activity was also considerably higher in homogenates of cells (predominantly smooth muscle) isolated from medial tissue by enzymatic dissociation with collagenase and elastase compared with homogenates of cells (mostly of connective tissue origin) from the adventitia. Histochemical staining resulting from SSAO activity (with benzylamine as substrate) occurred predominantly and intensely over the tunica media in rat aortic sections, although some occasional staining of adventitial sites was also observed. Staining was prevented by the SSAO inhibitors hydroxylamine (1 microM) and semicarbazide (1 mM), but not by the MAO inhibitor, clorgyline (1 mM). These results indicate that SSAO is associated predominantly, although not exclusively, with the smooth muscle cells in the rat aorta. Our findings that beta-aminopropionitrile (BAPN) is a reversible, competitive inhibitor (Ki around 2 X 10(-4)M) of SSAO, in contrast to the irreversible inhibition of the connective tissue lysyl oxidase by BAPN reported by others, provides further evidence that these enzymes are not identical.
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PMID:Vascular smooth muscle cells: a major source of the semicarbazide-sensitive amine oxidase of the rat aorta. 286 84

The catalysis of amine oxidation by lysyl oxidase has been probed to assess for the likely order of substrate binding and product release and to discriminate between mechanistic alternatives previously proposed for other copper-dependent amine oxidases using molecular oxygen as a substrate. Lineweaver-Burk plots revealed a pattern of parallel lines when the oxidation of n-butylamine was followed at different fixed concentrations of oxygen consistent with a "ping-pong" kinetic mechanism in which the aldehyde is produced and released before the binding of oxygen, the second substrate. Initial burst experiments revealed the ability of lysyl oxidase to form and release n-butyraldehyde in amounts stoichiometric with functional active site content in the absence of oxygen, consistent with the ping-pong kinetics obtained. Reciprocal plots of n-butylamine oxidation in the presence of fixed concentrations of the reaction products were consistent with a Uni Uni Uni Bi ping-pong kinetic mechanism with the aldehyde being the first, H2O2 the second, and ammonia the last departing product. Moreover, spectral studies of the oxidation of p-hydroxybenzylamine by lysyl oxidase indicated that the enzyme does not process the amine substrate to a noncovalently bound p-hydroxybenzaldimine intermediate subsequently to be hydrolyzed to p-hydroxybenzaldehyde. The kinetic mechanism of lysyl oxidase thus appears to be similar to those described for diamine oxidase and pig plasma monoamine oxidase.
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PMID:Reaction pathway of bovine aortic lysyl oxidase. 287 43

The present study investigated the possibility that pyrroloquinolinequinone (PQQ), an aromatic carbonyl recently indicated to be the carbonyl cofactor in bovine plasma amine oxidase, may also be present at the active site of lysyl oxidase. The absorption and resonance Raman spectra of the phenylhydrazones of bovine plasma amine oxidase, of peptides derived from the active site of bovine aorta lysyl oxidase, and of PQQ were very similar, indicating that the carbonyl cofactor of lysyl oxidase is PQQ or a compound which closely resembles PQQ.
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PMID:Evidence for pyrroloquinolinequinone as the carbonyl cofactor in lysyl oxidase by absorption and resonance Raman spectroscopy. 287 87

Modern data on types, physico-chemical properties, physiological role of copper-containing amine oxidase of blood vessels are reviewed. Properties of lysyl oxidase--specific copper-containing amine oxidase--are described. Importance of the enzyme for normal functions of connective tissue as well as alterations in the enzymatic activity under various pathological conditions are discussed. At the same time, properties and physiological functions of another copper-containing amine oxidase of blood vessels, which uses polyamines as substrate, are considered. Effect of the copper levels on content of polyamines in body is discussed.
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PMID:[Copper-containing amine oxidases of blood vessels (review of the literature)]. 288 71

Serum monoamine oxidase, diamine oxidase and lysyl oxidase-like activity were measured in patients with granuloma annulare (GA), necrobiosis lipoidica (NL) and diabetes mellitus. In diabetes, all enzyme measurements were raised by a factor of about 2 X 2, and in NL by a factor of about 1 X 5. The rise in patients with GA was small and only significant in the case of benzylamine monoamine oxidase. "Stiff' collagen would seem to link these three disorders and the present results suggest that these amine oxidases could be useful in monitoring collagen abnormality in diabetes and diabetes-associated disorders, particularly in the absence of chronic liver disease. A negative correlation was found between enzyme activity and blood glucose levels, thus collagen changes in these conditions may occur independently of elevated blood glucose levels. Possible involvement of these enzymes in angiopathy remains to be elucidated.
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PMID:Increased activity of serum amine oxidases in granuloma annulare, necrobiosis lipoidica and diabetes. 288 24


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