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)

We report two phenotypically similar patients with primary cutis laxa associated with deficiency of lysyl oxidase, an extracellular copper enzyme the gene for which is located on chromosome 5. Previous reports of this condition have had characteristic occipital projections, abnormality of copper metabolism and X-linked inheritance. The two reported patients have no occipital projections, normal copper metabolism, Wormian bones, and a pattern of inheritance consistent with the autosomal recessive inheritance of the lysyl oxidase gene.
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PMID:Congenital cutis laxa and lysyl oxidase deficiency. 911 98

The cuproenzymes lysyl oxidase, cytochrome-c oxidase, and superoxide dismutase are key factors in understanding the cardiac hypertrophy and cardiomyopathy associated with dietary copper restriction. The role of copper in cardiac lipid and energy metabolism as a consequence of changes in some of these enzyme activities in comparison with what is known about normal cardiac substrate utilization is discussed here. While the decrease in the nuclear encoded subunits of cytochrome-c oxidase in hearts from copper-deficient rats is known, new evidence suggests that other factors, such as ATP synthase metabolism may be exerting an influence upon this observation. While this review focuses on newer knowledge about energy and fatty acid metabolism in copper deficiency, the extracellular matrix is considered as well. This complex interplay of extracellular and cellular events in copper restriction is outlined as a model for further studies of this unique model of concentric hypertrophy.
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PMID:Newer findings on a unified perspective of copper restriction and cardiomyopathy. 927 Jul 15

It has been proposed that the oxidative modification of low density lipoprotein (LDL) is a key event in human atherogenesis. Copper ions can catalyse the oxidative modification of LDL in vitro and there is some evidence that they may also participate in the oxidation of LDL within the arterial wall. However, copper ions also form an intrinsic constituent of superoxide dismutase and caeruloplasmin, enzymes that may be involved in preventing oxidative injury. Atherosclerotic lesions frequently contain considerable quantities of extracellular matrix molecules. These may contribute to the expansion of the arterial neointima, causing luminal narrowing. They may also play a beneficial role by stabilising the plaque. Copper is an essential component of lysyl oxidase, an enzyme involved in the biosynthesis of collagen, which is a major constituent of the extracellular matrix. The impact of alterations in body copper status on atherogenesis is therefore difficult to predict. Experimental and epidemiological data are conflicting and therefore do not provide a clear resolution of this issue. We have reviewed the biochemical and cellular effects of copper ions that may play a role in atherogenesis.
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PMID:The possible role of copper ions in atherogenesis: the Blue Janus. 962 90

Lysyl oxidase is a copper-dependent enzyme involved in extracellular processing of collagens and elastin. Although it is known that copper is essential for the functional activity of the enzyme, there is little information on the incorporation of copper. In the present study we examined the insertion of copper into lysyl oxidase using 67Cu in cell-free transcription/translation assays and in normal skin fibroblast culture systems. When a full-length lysyl oxidase cDNA was used as a template for transcription/translation reactions in vitro, unprocessed prolysyl oxidase appeared to bind copper. To examine further the post-translational incorporation of copper into lysyl oxidase, confluent skin fibroblasts were incubated with inhibitors of protein synthesis (cycloheximide, 10 microg/ml), glycosylation (tunicamycin, 10 microg/ml), protein secretion (brefeldin A, 10 microg/ml) and prolysyl oxidase processing (procollagen C-peptidase inhibitor, 2.5 microg/ml) together with 300 microCi of carrier-free 67Cu. It was observed that protein synthesis was a prerequisite for copper incorporation, but inhibition of glycosylation by tunicamycin did not affect the secretion of 67Cu as lysyl oxidase. Brefeldin A inhibited the secretion of 67Ci-labelled lysyl oxidase by 46%, but the intracellular incorporation of copper into lysyl oxidase was not affected. In addition, the inhibition of the extracellular proteolytic processing of prolysyl oxidase to lysyl oxidase had minimal effects on the secretion of protein-bound 67Cu. Our results indicate that, similar to caeruloplasmin processing [Sato and Gitlin (1991) J. Biol. Chem. 266, 5128-5134], copper is inserted into prolysyl oxidase independently of glycosylation.
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PMID:Incorporation of copper into lysyl oxidase. 935 64

The lysyl oxidase-like (LOXL) gene is a new member of the lysyl oxidase family, a copper-dependent enzyme that is implicated in the crosslinking of collagen and elastin fibers. We have mapped the LOXL gene to chromosome 15q23, between STS markers D15S215 and GHLC.GCT7C09. This position corresponds to the q23 locus, not to the q24-25 locus suggested in a preliminary report.
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PMID:The human lysyl oxidase-like gene maps between STS markers D15S215 and GHLC.GCT7C09 on chromosome 15. 940 68

In order to elucidate the relationships between Zn and Cu and blood pressure, the present case-control study was carried out. Zn and Cu status was evaluated in 60 subjects, pharmacologically untreated, affected by mild stable hypertension and in 60 normotensives matched for sex, age and smoking habits. Different markers of Zn and Cu status, including serum, erythrocyte and urine levels of the two trace elements and activities of some Zn- or Cu-dependent enzymes (alkaline phosphatase, lactic dehydrogenase, superoxide dismutase and lysyl oxidase) were evaluated. No significant difference between hypertensives and normotensives was observed in the mean levels of Zn and Cu as well as in Zn- or Cu-dependent enzymes, though higher levels of serum copper were associated with increased risk of hypertension. Interesting relationships between the biological parameters investigated were observed in the hypertensive subjects. Inverse correlations between blood pressures and serum Zn were observed. Furthermore, blood pressure was inversely related to lysyl oxidase activity. These findings give further support to the hypothesis that an imbalance of Zn and Cu bioavailability may be associated to hypertensive condition.
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PMID:Zinc and copper status and blood pressure. 963 5

The moose (Alces alces L.) in an acid rain affected region in south-west Sweden has developed a complex disease with numerous clinical signs, most of which are consistent with those of secondary copper (Cu) deficiency and/or molybdenosis in cattle and sheep. The clinical signs of the moose disease reported to date include diarrhoea, anorexia, emaciation, achromotrichia, alopecia, sudden heart failure and osteoporosis. Findings at necropsy included mucosal oedema, atrophied lymphoid tissues of the mucous membranes of the alimentary tract, neuropathy, neuronal degeneration and uni- or bilateral corneal opacity. In a study of clinically healthy animals from the affected region in Sweden over a 12-year period (1982-1994), the hepatic Cu concentration decreased by 50% and the liver and kidney cadmium (Cd) concentration decreased by 25-35%, while the molybdenum (Mo) concentration increased by 20-40%. These changes are probably related to an increase in the pH of the soil and water in the moose environment and a consequent change in the uptake of these elements by the plants consumed by the moose. It is noteworthy that the occurrence of the disease in the mid 1980s coincided with increased liming undertaken to counteract the noxious effects of acid rain in this region. Clinical signs and lesions of the moose disease resemble those reported for Cu deficiency and/or molybdenosis in cattle and sheep. To elucidate the complex, multi-faceted clinical signs of the moose disease, the clinical signs and necropsy findings are discussed in relation to the biochemical functions of certain well-known Cu-dependent enzymes, e.g. depigmentation of hair due to depressed tyrosinase activity, osteoporosis by depressed lysyl oxidase activity, sudden heart failure due to decreased activity of lysyl oxidase, cytochrome c oxidase and Cu/Zn-superoxide dismutase; in addition, mucosal lesions and ulcerations due to loss of activity of diamine oxidase as well as of lysyl oxidase and cytochrome c oxidase. It is concluded from the present findings that the moose disease is most probably a Cu deficiency and/or a molybdenosis-type syndrome.
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PMID:'Mysterious' moose disease in Sweden. Similarities to copper deficiency and/or molybdenosis in cattle and sheep. Biochemical background of clinical signs and organ lesions. 949 61

Type IX of the Ehlers-Danlos syndrome (E-D IX) and the Menkes syndrome are X-linked recessively inherited disorders characterized by abnormalities in copper metabolism. These abnormalities are associated with a severe reduction in the activity of lysyl oxidase, the extracellular copper enzyme that initiates crosslinking of collagens and elastin. No increase in this deficient enzyme activity was obtained when culture media from fibroblasts of patients with E-D IX or the Menkes syndrome were incubated with copper under various conditions in vitro. A distinct, although small, increase in lysyl oxidase activity was obtained, however, when copper-supplemented media were used during culturing of the fibroblasts, although even under these conditions, the enzyme activity in the media from the affected cells remained markedly below that of the controls. Immunoprecipitation, dot-blotting, and immunoperoxidase staining experiments with antisera to human lysyl oxidase indicated that fibroblasts from patients with E-D IX or the Menkes syndrome do not secrete into their medium, or contain inside the cell, any significant amounts of a copper-deficient, catalytically inactive lysyl oxidase protein. These findings appear to be consistent with the hypothesis that synthesis of the lysyl oxidase protein itself is impaired. The possibility is not excluded, however, that a copper-deficient enzyme protein may be synthesized in normal amounts but become degraded very rapidly inside the cell. The failure to obtain any large increase in the deficient lysyl oxidase activity upon various forms of copper administration suggests that it may not be possible to obtain any significant improvement in the connective tissue manifestations of these disorders by copper therapy.
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PMID:Type IX Ehlers-Danlos syndrome and Menkes syndrome: the decrease in lysyl oxidase activity is associated with a corresponding deficiency in the enzyme protein. 955 68

Protein-lysine 6-oxidase (lysyl oxidase) is a cuproenzyme that is essential for stabilization of extracellular matrixes, specifically the enzymatic cross-linking of collagen and elastin. A hypothesis is proposed that links dietary copper levels to dynamic and proportional changes in lysyl oxidase activity in connective tissue. Although nutritional copper status does not influence the accumulation of lysyl oxidase as protein or lysyl oxidase steady state messenger RNA concentrations, the direct influence of dietary copper on the functional activity of lysyl oxidase is clear. The hypothesis is based on the possibility that copper efflux and lysyl oxidase secretion from cells may share a common pathway. The change in functional activity is most likely the result of posttranslational processing of lysyl oxidase. Copper is essential for organic cofactor formation in amine oxidases such as lysyl oxidase. Copper-containing amine oxidases have peptidyl 2,4,5 tri(oxo)phenylalanine (TOPA) at their active centers. TOPA is formed by copper-catalyzed oxidation of tyrosine, which takes place as part of Golgi or trans-Golgi processing. For lysyl oxidase, recent evidence (Science 1996;273:1078-84) indicates that as an additional step, a lysyl group at the active center of lysyl oxidase reacts with TOPA or its precursor to form lysyl tyrosylquinone.
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PMID:Copper, lysyl oxidase, and extracellular matrix protein cross-linking. 958 42

Research spurred by the discovery of pyrroloquinoline quinone (PPQ) in 1979 led to the discovery of four additional oxidation-reduction (redox) cofactors, all of which result from transmogrification of amino acyl side chains in respective enzymes. These cofactors are (a) topa quinone in copper-containing amine oxidases, enzymes found in nearly all forms of life, including human; (b) lysyl topa quinone of the copper protein lysyl oxidase, an enzyme required for proper cross-linking of collagen and elastin; (c) tryptophan tryptophylquinone of alkylamine dehydrogenases from gram-negative soil bacteria; and (d) the copper-complexed cysteinyltyrosyl radical of fungal galactose oxidase. Originally, PQQ was thought to be a covalently bound cofactor in numerous enzymes from eukaryotes and prokaryotes. Today, PQQ is only found as a noncovalent cofactor in bacterial enzymes. The ubiquity of PQQ in the environment and its steady accessibility in the human diet has raised questions concerning its role as a vitamin, or an essential or helpful nutrient. The relevance to nutrition, medicine, and pharmacology of PQQ, topa quinone, lysyl topa quinone, tryptophan trytophylquinone, the galactose oxidase cofactor, and the enzymes harboring these cofactors are discussed in this review.
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PMID:Newly discovered redox cofactors: possible nutritional, medical, and pharmacological relevance to higher animals. 970 22


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