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)

Aldehyde-deficient non-crosslinked collagen obtained from lathyritic rats and collagen from penicillamine-treated rats, which is not deficient in aldehydes but the crosslinking of which is also inhibited, were implanted into the peritoneal cavity of hypophysectomized rats using the diffusion chamber technique. The enzyme lysyl oxidase which catalyses the aldehyde formation in certain lysyl residues of collagen and elastin was extracted from the skin of hypophysectomized rats. The activity of the enzyme was determined following its incubation with an L-[4,5-3H] lysine-labeled elastin substrate prepared from aortas of 17-day-old chick embryos. The result showed that the aldehyde deficient collagen did not crosslink while in the hypophysectomized animal indicating the lack of active lysyl oxidase in the rats. The enzyme activity in the skin of hypophysectomized animals was markedly reduced as compared with the controls indicating directly the dependance of lysyl oxidase activity on pituitary gland hormones.
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PMID:Lysyl oxidase: a pituitary hormone-dependent enzyme. 0 16

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

D-Pencillamine is believed to inhibit collagen cross-link biosynthesis by forming thiazolidine rings with lysyl-derived aldehydes that are intermediates in bifunctional cross-link synthesis. Recently, we showed that aldehyde biosynthesis catalyzed by lysyl oxidase occurs after the onset of fibril formation and that nascent aldehydes form Schiff-base cross-links rapidly in fibrils. This suggested that the accessibility of D-penicillamine to most aldehydes formed during cross-link synthesis might be limited. To study this, reconstituted chick bone collagen fibrils were incubated in vitro with highly purified lysyl oxidase and D-penicillamine. As reported in previous studies in vivo, allysine content increased and polyfunctional cross-link synthesis decreased with D-penicillamine. However, the concentration of bifunctional cross-links increased rather than decreased due to a 2-fold increase in N6:6'-dehydro-5,5'-dihydroxylysinonorleucine. Hydroxyallysine, an intermediate in formation of this Schiff base, decreased. A time study indicated that allysine levels increased primarily after the bulk of Schiff base synthesis. These results indicate that D-penicillamine does not inhibit bifunctional cross-link synthesis as previously suggested. Its principal effect is to block synthesis of polyfunctional cross-link products from Schiff base cross-link precursors and to cause accumulation of these precursors. This effect may be due to interference with the close molecular packing required for polyfunctional cross-link synthesis. These results also suggest a mechanism for the relative insensitivity of tissues such as bone with high hydroxylysine content to D-penicillamine. In this study, D-penicillamine caused selective accumulation of allysyl and not hydroxyallysyl residues. In bone as opposed to soft tissues, hydroxyallysyl residues are intermediates in synthesis of almost all cross-links.
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PMID:Collagen cross-linking. Effect of D-penicillamine on cross-linking in vitro. 1 66

A protective and curative effect of some flavonoids on collagen maturation in lathyrism has been previously demonstrated. This action appeared to involve cross linking of collagen. This paper deals with the effect in vitro of flavonoids and flavonoid-copper complexes on the oxidative deamination of lysine epsilon-amino groups in [4,5-3H]-lysine-labelled elastin. Flavonoids alone do not affect the reaction but it is evident that some flavonoid copper complexes are strongly effective: the aldehyde groups that are quickly formed then enable cross linking to occur. The lysine epsilon-amino groups of elastin are specifically concerned: in fact no effect was observed on free [4,5-3H]-lysine or on [4,5-3H]-lysine-labelled proteins obtained from mouse liver. The lysyl oxidase seems to interfere with the flavonoid-copper complees to regulate the oxidative deamination of lysine epsilon-amino groups.
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PMID:Influence of flavonoid-copper complexes on cross linking in elastin. 56 63

Nutritional copper deficiency effects marked changes in the crosslinking of collagen and elastin, presumably in relationship to copper's role as a cofactor for lysyl oxidase. Lysyl oxidase controls one of the initial steps in the crosslinking of elastin and collagen, i.e., the conversion of peptidyl lysine or hydroxylysine residues to peptidyl alpha-aminoadipic-delta-semialdehyde derivatives. Once lysine-derived aldehydic functions in collagen and elastin are formed, crosslinks occur via aldol and Schiff-base type condensations. A decrease in the degree of crosslinking results in changes in the biomechanical properties of both collagen- and elastin-rich tissues. Some of these changes are described with respect to chick bone and aorta. Likewise, penicillamine blocks crosslinking reactions. In this case, however, it is probably because of the formation of thiazolidine complexes between penicillamine aldehydic functions. The administration of penicillamine at different levels to young growing chicks allows the isolation of fibrous insoluble elastin varying in aldehyde content.
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PMID:Nutritional copper deficiency and penicillamine administration: some effects on bone collagen and arterial elastin crosslinking. 90 29

Lysyl oxidase (EC 1.4.3.13) is a copper-dependent enzyme acting principally on collagen and elastin catalyzing the formation of aldehyde cross-links. It is also believed to possess a tumor suppressor activity as the anti-oncogene of ras. While rat, human, and mouse lysyl oxidase cDNAs have been cloned, little is known about the structure of the gene, its organization, or regulation. This paper describes the cloning of an intronic segment of the human lysyl oxidase gene. Sequence analysis defined the location of an intron that separates the prepro-coding segments from the segment encoding the catalytic domain. Genomic restriction mapping and gene copy number data established that multiple lysyl oxidase mRNA transcripts originate from a single gene and thus are products of alternative splicing. Northern analysis of adult and fetal fibroblast RNA showed a dominant approximately 4.3-kilobase lysyl oxidase mRNA transcript that varied in abundance as a function of cell line. These data are consistent with a complex mechanism regulating the expression of the lysyl oxidase gene.
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PMID:Characterization of the human lysyl oxidase gene locus. 135 76

Lysyl oxidase, which cross-links collagen and elastin, was obtained from chick embryo bone and cartilage and its substrate, elastin, from aorta. The enzyme was studied using an improved assay which enabled the stability of the substrate to be monitored. The enzyme was fully inhibited in vivo by beta-aminopropionitrile, semicarbazide, thiosemicarbazide and isoniazid and in vitro by beta-aminopropionitrile and semicarbazide but only partially by thiosemicarbazide and isoniazid. Penicillamine, which solubilizes collagen by labilizing Schiff base cross-links in vivo and which prevents stable cross-link formation in vitro indirectly by binding to aldehyde groups on collagen, was shown to have no direct inhibitory effect on lysyl oxidase in vivo or in vitro. Homocysteine, which also solubilizes collagen by a mechanism similar to penicillamine does not inhibit lysyl oxidase either in vivo or in vitro. Pyridoxal reversed the inhibition of lysyl oxidase by semicarbazide and isoniazid in vivo but was unable to reverse that produced by either beta-aminopropionitrile or thiosemicarbazide. These results can be explained by the presence of a sulphydryl group near the active site of lysyl oxidase, which can form a complex with the nitrile group on beta-aminopropionitrile or with the thiol group on thiosemicarbazide leading to irreversible inhibition.
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PMID:Inhibition of chick embryo lysyl oxidase by various lathyrogens and the antagonistic effect of pyridoxal. 135 70

In histochemical model studies, aminoacetonitrile and 3-aminopropionitrile can form hydrolysis-stable azomethines (Schiff bases) with periodate-induced aldehyde groups of tissue slices. Both substances and triethylentetramine do not inhibit the histochemical monoaminoxidase activity, they even can act as substrates of this enzyme. These substances cause an inhibition of the histochemical aminopeptidase M activity, but this inhibition was recognized as a methodological error due to the formation of complexes between diazonium salts and aliphatic amines. The results indicate that the inhibition of the lysyl oxidase will not be the only mechanism of action of lathyrogenic substances.
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PMID:[Histochemical model investigations of the action mechanisms of lathyrogenic substances]. 171 23

Lysyl oxidase initiates the cross-linking of collagen and elastin by catalyzing the formation of the lysine-derived aldehyde. We cloned three hybridoma cell lines which secrete monoclonal antibodies to human lysyl oxidase. The localization of lysyl oxidase was investigated in various tissues and in cultured cells using an immunofluorescent antibody method. Antibodies showed a strong immunostaining in the aorta and dermal connective tissue suggesting a close relation to elastin and collagen. Fibroblasts, chondrocytes, and smooth muscle cells also yielded a marked positive immunoreaction as did a variety of nonfibroblastic cells such as endothelial cells, basal cells, biliary epithelial cells, and glomerular epithelial cells. In cultured cells, including human fibroblasts, an intense immunoreaction manifested as fine, filamentous structures in the cytoplasm. It is suggested that lysyl oxidase is associated with cytoskeletal protein.
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PMID:Immunohistochemical localization of lysyl oxidase with monoclonal antibodies. 197 33

The spectral and catalytic properties of the copper cofactor in highly purified bovine aortic lysyl oxidase have been examined. As isolated, various preparations of purified lysyl oxidase are associated with 5-9 loosely bound copper atoms per molecule of enzyme which are removed by dialysis against EDTA. The enzyme also contains 0.99 +/- 0.10 g atom of tightly bound copper per 32-kDa monomer which is not removed by this treatment. The copper-free apoenzyme, prepared by dialysis of lysyl oxidase against alpha,alpha'-dipyridyl in 6 M urea, catalyzed neither the oxidative turnover of amine substrates nor the anaerobic production of aldehyde at levels stoichiometric with enzyme active site content, thus contrasting with the ping pong metalloenzyme. Moreover, the spectrum of the apoenzyme was not measurably perturbed upon anaerobic incubation with n-butylamine, while difference absorption bands were generated at 250 and 308 nm in the spectrum of the metalloenzyme incubated under the same conditions. A difference absorption band also developed at 300-310 nm upon anaerobic incubation of pyrroloquinoline quinone, the putative carbonyl cofactor of lysyl oxidase, with n-butylamine. Full restoration of catalytic activity occurred upon the reconstitution of the apoenzyme with 1 g atom of copper/32-kDa monomer, whereas identical treatment of the apoenzyme with divalent salts of zinc, cobalt, iron, mercury, magnesium, or cadmium failed to restore catalytic activity. The EPR spectrum of copper in lysyl oxidase is typical of the tetragonally distorted, octahedrally coordinated Cu(II) sites observed in other amine oxidases and indicates coordination by at least three nitrogen ligands. The single copper atom in the lysyl oxidase monomer is thus essential at least for the catalytic and possibly for the structural integrity of this protein.
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PMID:Structural and catalytic properties of copper in lysyl oxidase. 197 46


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