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)

Exposure of [3H]-lysine labeled elastin to either purified myeloperoxidase plus H2O2 and halides or human neutrophils plus phorbol myristate acetate resulted in oxidation of lysine side chains quantitated as 3H2O release. In both the enzyme and cell system oxidation was blocked by azide, cyanide or catalase, but not by beta-aminopropionitrile, an inhibitor of lysyl oxidase. Myeloperoxidase-deficient neutrophils were ineffective unless exogenous myeloperoxidase was added. These data provide a biochemical basis for inflammatory changes in connective tissue proteins mediated by oxidant secretory products of neutrophils.
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PMID:Oxidation of lysine side-chains of elastin by the myeloperoxidase system and by stimulated human neutrophils. 300 20

The severity of pulmonary emphysema can be affected by exposure to cigarette smoke in several ways. Inactivation of alpha-1-antitrypsin and recruitment of leukocytes to lung airways shifts the protease-antiprotease balance towards increased elastolytic activity. The present study demonstrates an additional effect of cigarette smoke inhalation and retardation of the repair process and of the neosynthesis of cross-linked elastin. Hamsters with elastase-induced emphysema, exposed to cigarette smoke for 1 wk immediately after elastase administration, showed a 40% reduction of 14C-lysine incorporation into the elastin-specific cross-links, desmosine, and isodesmosine. Concomitantly, there was a decrease in the level of lung lysyl oxidase to that observed in uninjured control animals, in sharp contrast to the sevenfold increase in lysyl oxidase activity in hamsters with elastase-induced emphysema recovering under atmospheric conditions. These findings suggest that impairment of the production of lysyl oxidase and the resynthesis of cross-linked elastin by smoke inhalation exacerbates alveolar destruction.
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PMID:Cigarette smoke impairs elastin resynthesis in lungs of hamsters with elastase-induced emphysema. 392 58

Collagen analysis of articular cartilage and subchondral bone was performed on femoral heads obtained from patients of late stage of aseptic necrosis (ANF) (4 cases), and osteoarthritis (OA) (7 cases). In articular cartilage of both diseases, there was not observed any difference in the solubility of collagen compared with normal articular cartilage. However, collagen contents determined by hydroxyproline analysis showed a decrease in both diseases; this tendency was prominent in OA. On the other hand, copper contents showed an increase in ANF while there was a decrease in OA; the fact may suggest that lysyl oxidase acts actively on the formation of a precursor of cross-links in collagen matrix of articular cartilage in ANF. In subchondral bone of both diseases, collagen contents showed an increase in OA, and a decrease in ANF compared with normal subchondral bone. However the solubility of collagen has increased in both diseases. Moreover, lysine hydroxylation and copper contents showed an increase in both OA and ANF; these findings suggest that repairing reaction of the pathological lesion by proliferation of undifferentiated tissue remained even in late stage of the disease. In this paper, the author also discussed about the connective tissue metabolism of these two diseases by determination the types of collagen molecules of pathological cartilage and bone.
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PMID:[Experimental study on the development of aseptic necrosis of femoral head--with comparison of osteoarthritis of the hip in collagen metabolism]. 405 23

Synthetic repeat polypeptides analogous in sequence to the valine-rich regions of elastin have been tested as substrates for purified bovine aorta lysyl oxidase. These polypeptides, HCO(phi-Pro-Gly-Gly)n-Val-OMe, HCO(Val-Pro-Gly-phi-Gly)n-Val-OMe, and HCO-Val-(Ala-Pro-Gly-phi-Gly-Val)n-OMe, where phi = Val or Lys at approximately a 4:1 ratio and where n greater than or equal to 40, are models of the tetra-, penta-, or hexapeptide repeat sequences found in elastin. alpha-Aminoadipic delta-semialdehyde is generated in each of these upon incubation with lysyl oxidase at 37 degrees C, whereas the aldol and anhydrolysinonorleucine bifunctional cross-linkages were formed only in the incubation of enzyme with polypentapeptide. Incubation of the polypentapeptide at 55 degrees C, which enhances coacervation of the peptide, increases aldehyde formation and generates a much higher ratio of cross-linkages to aldehyde than occurred at 37 degrees C. These results demonstrate that lysyl oxidase can oxidize lysine in synthetic polypeptides and suggest important conformational aspects of lysyl oxidase substrates which may control substrate potential as well as the ability of peptidyl aldehyde, once formed by the enzyme, to condense to cross-linkage products.
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PMID:Repeat polypeptide models of elastin as substrates for lysyl oxidase. 610 68

Copper's role in connective tissue is linked to the enzyme lysyl oxidase. From a biochemical perspective, copper is a cofactor for the enzyme and a determinant of its activity in connective tissues. Lysyl oxidase catalyses a post-translational oxidation of certain lysine and hydroxylysine residues. The peptidyl aldehydes so formed become active centres for the formation of cross-links in collagen and elastin. Less well understood is how copper controls the steady-state activity of lysyl oxidase; the enzyme fails in copper deficiency. Giving copper to a deprived animal increases lysyl oxidase activity in aortic tissue. Such activation in vivo appears to require caeruloplasmin. Suspending aortic tissue in a copper-enriched growth medium also activates lysyl oxidase provided that tissue structure is kept intact. Activation in vitro occurs with the binding of copper to a large-molecular-weight component, presumably the enzyme. Binding will not occur if protein synthesis is blocked. These studies clearly show that the synthesis of mature elastin and collagen can be controlled by the availability of copper. They further suggest that transport of copper to aortic tissue and its engagement to lysyl oxidase are linked to the synthesis or lysyl oxidase, an extracellular carrier, or both.
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PMID:Copper and the synthesis of elastin and collagen. 611 May 24

The oxidation of an elastin substrate by highly purified bovine aortic lysyl oxidase (LO) is markedly influenced by amphiphilic molecules known to bind to elastin. Negatively charged elastin ligands, including fatty acids, bile salts or sodium dodecyl sulfate can completely inhibit the oxidation of lysine in elastin, the cationic amphiphilic ligands stimulate the enzymatic reaction five-fold, while small hydrophilic molecules of either charge or neutral detergents have no effect. In addition, evidence has been obtained that changes in the conformation of a synthetic polypeptide substrate markedly alter its susceptibility to LO. The coacervated state of the substrate is most readily oxidized and crosslinked by the enzyme. These results point to the importance of small ligands, electrostatic charge, and conformation as substrate-directed influences which can control the expression of LO activity.
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PMID:Substrate-directed modulation of elastin oxidation by lysyl oxidase. 611 10

Cultures of rabbit aortic smooth muscle (RSM) cells are a valuable model system for studying production and metabolism of connective tissue components. This report describes various assay procedures for lysyl oxidase, the enzyme responsible for deaminating lysine residues to give aldehyde cross-link precursors, in culture medium from these cells. Studies of the medium enzyme from second-passage RSM cells indicate that approximately 40% of the total enzyme activity in the flask of cells is in the medium. The medium enzyme levels are replenished quite rapidly following refeeding, and enzyme levels in the medium appear to be feedback controlled. The mechanism for this control is unknown at present. Multiple refeeding experiments in which the medium was changed every 2-4 h for up to 40 h indicate that these cells are cap]able of producing large amounts of enzyme and are capable of altering enzyme production and secretion quite rapidly in response to changes in their environment. Protein synthesis inhibitor studies with cycloheximide suggest that the major portion of the enzyme released into the medium following refeeding is newly synthesized although a pool of latent enzyme is also present. As in intact tissue, extraction of the enzyme from the cell layer requires strong denaturing reagents such as 4 M urea. These results suggest that the production of lysyl oxidase is closely regulated and is very responsive to changes in the external environment of the cells. This cell culture system appears to be an excellent one to study the production of lysyl oxidase and its role in connective tissue fibrillogenesis.
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PMID:Measurement of medium lysyl oxidase activity in aorta smooth muscle cells. Effects of multiple medium changes and inhibition of protein synthesis. 611 72

Lysyl oxidase initiates the covalent cross-linking of elastin and collagen by oxidizing lysine residues in these proteins to alpha-aminoadipic-delta-semialdehyde. Sequences surrounding susceptible lysines in elastin are considerably different from those in collagen and yet the same enzyme can oxidize both substrates. Possible bases of the specificity have been explored assaying for H2O2 release accompanying the oxidation of synthetic peptide and protein substrates. Rates of oxidation of random co-polymers were maximal with (Ala,Lys)n and decreased in the order (Val,Lys)n greater than (Leu,Lys)n greater than (Lys)n greater than (Phe,Lys)n greater than (Tyr,Lys)n. The ordered polymer (Ala-Lys-Glu)n was oxidized at only 3% of the rate of (Ala,Lys)n, implying inhibition by peptidyl glutamate. Consistent with this conclusion, kinetic analyses using ordered oligopeptides revealed that, relative to Ala-Ala-Lys-Ala-Ala, Km is increased 9.3-fold for lysine in Ala-Ala-Lys-Glu-Ala-Ala, 2.5-fold in Ala-Ala-Lys-Arg-Ala-Ala, and 1.8-fold in Ala-Ala-Glu-Lys-Ala-Ala. Tyrosine C-terminal to lysine in such peptides also increases Km 5-fold. In addition, lysyl oxidase oxidized lysine in various proteins with basic isoelectric points and was much less or not active against various acidic proteins. Lysyl oxidase was inactive against native bovine serum albumin but effectively oxidized albumin if albumin carboxyl functions were first amidated by chemical modification. These results suggest that peptides bind to lysyl oxidase in a preferred directional sense and indicate-that net anionic character as well as the specific position of anionic residues in substrates can selectively effect substrate potential. Implications of these results for the oxidation of elastin and collagen are discussed.
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PMID:Influence of sequence and charge on the specificity of lysyl oxidase toward protein and synthetic peptide substrates. 614 51

The elastic properties of many tissues such as the lung, dermis, and large blood vessels are due to the presence of elastic fibers in the extracellular space. These fibers have been shown by biochemical and ultrastructural analysis to be comprised of two distinct components, a more abundant amorphous component and the microfibrillar component. The microfibrillar component is found in 10- to 12-nm fibrils which are located primarily around the periphery of the amorphous component but, to some extent, interspersed within it. The protein, elastin, makes up the highly insoluble amorphous component and is responsible for the elastic properties. Elastin is found throughout the vertebrate kingdom except for very primitive fish and possesses an unusual chemical composition consonant with its characteristic physical properties. Elastin is composed largely of glycine, proline, and other hydrophobic residues and contains multiple lysine-derived cross-links, such as the desmosines, which link the individual polypeptide chains into a rubber-like network. The intervening, hydrophobic regions of the polypeptide chains between the cross-links are highly mobile, and the elastic properties of the fibers can be described in terms of the theory of rubber elasticity. Recent application of recombinant DNA techniques has led to further understanding of the structure of elastin. Analyses of the bovine and human elastin genes have demonstrated that the hydrophobic and cross-linking domains are encoded in separate exons. These exons tend to be small, varying from 27 to 114 base pairs, and are separated by large intervening sequences. Furthermore, DNA sequence analysis has demonstrated that the elastin molecule contains two cysteine residues which were not previously identified near the carboxy terminus and which may be important in the interaction of elastin with other extracellular matrix proteins. Further DNA sequencing should determine the complete amino acid sequence of elastin. Biosynthetic studies and in vitro translation of elastin mRNA have demonstrated that a 72,000-dalton polypeptide, designated tropoelastin, is the initial translation product. Analysis of several developing systems has demonstrated that elastin synthesis is controlled by the level of elastin mRNA. After packaging into membrane-bound vesicles in the Golgi apparatus, tropoelastin is secreted by exocytosis into the extracellular space where it is cross-linked by a copper-requiring extracellular enzyme, lysyl oxidase. Elastin can be solubilized only by proteases that have consequently been designated elastases, although these are general, powerful proteases that can hydrolyze numerous proteins.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Elastin: relation of protein and gene structure to disease. 615 Jan 37

Collagens extracted from bones, cartilage, dermis, and dura mater of an infant with type II (lethal perinatal) osteogenesis imperfecta were evaluated with respect to chain composition and chemical characteristics of their constituent chains. The results indicated that the various types of collagen were present in the indicated tissues in proportions that approximated normal tissues. Nevertheless, the constituent chains of collagens extracted from dermis, i.e., alpha 1(I), alpha 2(I), alpha 1(III), alpha 1(V), and alpha 2(V), chromatographed on carboxymethyl cellulose as though they possessed substantially lower overall positive charge than the homologous chains of normal tissues. Amino acid analyses of the chains confirmed this observation and showed that the chains lacked five to seven residues of lysine (plus hydroxylysine). It was subsequently shown that the apparent deficiency in lysyl residues was due, at least in part, to the presence of unusually high levels of allysine , a cross-link precursor formed from peptide-bound lysine under the catalytic action of lysyl oxidase. These results, in conjunction with previous results obtained on collagens from type II osteogenesis imperfecta tissues, suggest that aberrant fibril formation in this syndrome allows increased lysyl oxidase activity.
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PMID:An unusual pattern of peptide-bound lysine metabolism in collagen from an infant with lethal perinatal osteogenesis imperfecta. 642 76


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