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)

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

Copper deficiency can reduce the productivity of livestock. The effect of copper deficiency on a number of copper enzymes and copper-dependent systems is discussed, to highlight the areas where their role needs to be clarified. Special reference is made to cytochrome c oxidase, lysyl oxidase, superoxide dismutase and endoplasmic reticulum enzymes and to their role in the expression of disease. The modification of microbiological insult by a change in superoxide dismutase activity without any other direct metabolic consequences is discussed, to introduce the concept of an external challenge being necessary before any effect of an otherwise sub-clinical copper deficiency is observed. The changes in activity of the various copper enzymes are described in clinical and experimentally induced copper deficiency in sheep and cattle, two species in which copper deficiency can have economic consequences. The diagnostic value of various blood markers, such as copper, caeruloplasmin and erythrocyte superoxide dismutase is discussed. The measured degree of hypocupraemia is related to different types of sampling (e.g. plasma or serum), physiological status (e.g. in the pre- and postpartum cow), changes that occur in the neonate, and also to the effect of the acute-phase reaction. The use of erythrocyte superoxide dismutase as a marker for the copper status of sheep and cattle is compared with more conventional markers such as plasma concentration of copper. The use of blood markers to map the extent and location of hypocupraemia (due to reduced copper intake or availability) among suckler (beef) herds in Northern Ireland is also discussed.
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PMID:Copper deficiency in ruminants. 611 May 25

Lysyl oxidase activity against both collagen and elastin substrates has been examined in the culture medium of skin fibroblasts derived from unrelated patients with Menkes' syndrome and from control subjects. The medium of three Menkes' fibroblast lines showed 3--30% of the activity present in the medium of control fibroblasts, against a purified collagen substrate. Lysyl oxidase activity in the culture medium of two of the Menkes' fibroblast lines was also examined by using a crude aortic-elastin substrate and was similarly decreased in comparison with that in the medium of control fibroblasts. Lysyl oxidase activity in the medium of a fourth fibroblast line, derived from a foetus with Menkes' syndrome, was 42% of that in the medium of control fibroblasts derived from a 1-day-old baby against a collagen substrate, and 26% of that in control fibroblast medium against an elastin substrate. The copper content of the cell layers of the Menkes' fibroblast cultures was elevated in comparison with normal fibroblast cultures, as has previously been reported to be characteristic of such cells. It is suggested that the decrease in lysyl oxidase activity would help to explain the connective tissue defects observed in Menkes' syndrome, and that this reduction, in conjunction with the elevated concentrations of cellular copper, would support the hypothesis that a functional intracellular copper deficiency exists in Menkes' syndrome.
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PMID:Reduced lysyl oxidase activity in skin fibroblasts from patients with Menkes' syndrome. 611 84

We have studied the effect of L-ascorbic acid (vitamin C) on copper metabolism using copper-deficient chicks and the activation of lysyl oxidase copper-dependent enzyme, to assess bioavailability of copper. When administered intraperitoneally with (or 75 minutes before) CuSO4, L-ascorbate significantly impared the effectiveness of copper to restore lysyl oxidase activity in deficient chicks. L-ascorbate given 75 minutes after CuSO4 (i.e., in the post-absorption period), however, produced a substantial increase in copper-induced enzyme activation. L-ascorbate by itself showed no direct stimulating effect in deficient chicks. When the L-ascorbate was given to chicks that had received adequate dietary copper, there was a strong rise in ceruloplasmin and a slight, but significant increase in lysyl oxidase. An increase in ceruloplasmin in response to copper was also seen in deficient chicks and L-ascorbate also augmented that increase. Substituting D-isoascorbic acid for antagonistic properties of L-ascorbic acid on copper metabolism, but they also reveal possible sterospecific postabsorption roles for L-ascorbate in the metabolism of copper.
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PMID:A postabsorption effect of L-ascorbic acid on copper metabolism in chicks. 611 9

Biochemical abnormalities were studied in two brothers with bladder divericulas, inguinal hernias, slight skin laxity, and hyperelasticity and skeletal abnormalities including occipital exostoses. Lysyl oxidase activity was low in the medium of cultured skin fibroblasts, this abnormality being accompanied by reduced conversion of the newly synthesized collagen into the soluble form. Copper concentrations were markedly elevated in the cultured skin fibroblasts, but decreased in the serum and hair. Serum cerulophasmin levels were also low. The reduced lysyl oxidase activity is suggested to be responsible for ther clinical manifestations, but the deficiency in this copper-dependent enzyme may be secondary to the abnormalities in the metabolism of the cation. Nevertheless, a mutation directly affecting both lysyl oxidase and an intracellular copper transport protein cannot be excluded. The disease is tentatively classified as one subtype of the Ehlers-Danlos syndrome.
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PMID:Abnormal copper metabolism and deficient lysyl oxidase activity in a heritable connective tissue disorder. 612 Sep 54

A mild form of emphysema was produced in pigs raised on a copper-deficient, zinc-supplemented diet. The copper-requiring enzyme, lysyl oxidase, catalyzes the cross-linking of tropoelastin into mature elastin. Zinc further inhibits the activity of lysyl oxidase. Lungs from animals raised on copper-deficient, zinc-supplemented diets of demonstrate perforations in alveolar walls and diminished amounts of elastin bronchi and pulmonary arteries. Mean linear intercepts are greater and alveolar internal surface areas are less than those in control animals, fulfilling the generally accepted definition of emphysema. Physiologic confirmation is provided by a leftward shift of the saline volume-pressure curves when compared with those in control animals. Ultrastructurally, the alveolar walls are effaced and pores of Kohn are enlarged. There are areas in which elastin is absent leaving remnant microfibrils, and there are other changes consistent with active elastin synthesis. Biochemical data demonstrate no difference in elastin content as micrograms/ml of fat-free dry weight but do demonstrate increased collagen content in experimental animal lungs compared with that in control lungs. Ultrastructural similarities to enzyme-induced models of emphysema suggest the presence of elastin degradation in our model. We speculate that although the copper-deficient, zinc-supplemented state may stimulate protein synthesis in general, elastin is being degraded by endogenous means, but collagen is not.
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PMID:A copper-deficient, zinc-supplemented diet produces emphysema in pigs. 612 18

D-penicillamine, added to a low copper diet fed through pregnancy or given by gavage to pregnant rts which were on a copper-deficient or a normal diet produced fetal resorptions and malformations. Doses of 300 to 400 mg per day for 6 days (days 9-14 or gestation) with a diet normal for copper prevented maternal weight gain and at 350 or 400 mg/day caused fetal death on day 16 or 17. Forty percent of offspring had tracheobronchomegaly and 42% had cystic lungs. Associated abnormalities included pleural hemorrhages, dilated esophagi, and anaerated lungs. The lungs had large, poorly formed, thick-walled acini without partitioning and a thick rim of connective tissue around vessels and bronchi. At the higher doses, all members of one of 12 litters had angulation of the spine and half the members of another litter had cleft palates. A postulated mechanism for these alterations in pulmonary connective tissue productive of malformations which model human tracheobronchomegaly and cystic lungs, is interference with lysyl oxidase, a copper-requiring enzyme, which cross-links elastin.
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PMID:Neonatal deaths and pulmonary dysplasia due to D-penicillamine in the rat. 612 15

beta-Aminopropionitrile (BAPN) is a potent irreversible inhibitor of lysyl oxidase, the enzyme which initiates cross-linkage formation in elastin and collagen. The initial interaction of BAPN with aortic lysyl oxidase is competitive with elastin or alkyl amine substrates. Irreversible inhibition develops in a time- and temperature-dependent fashion upon incubation of enzyme with BAPN in the absence of substrate with a limiting inactivation rate constant of 0.16 min-1 and a KI of 6 microM at 37 degrees C. The labeled carbons of [1,2-14C]BAPN and [3-14C]BAPN covalently bind to the enzyme to equivalent extents and in parallel with the development of inactivation, negating the possibility that the nitrile moiety is eliminated from BAPN by enzymatic action. The copper content of the enzyme is not significantly altered upon interaction with BAPN. The extent of labeling by [14C]BAPN is reduced by prior treatment of the enzyme with carbonyl-modifying reagents, suggesting the possibility of enzyme-inhibitor Schiff base formation. However, BAPN is not processed to a free aldehyde product upon incubation with lysyl oxidase. A mechanism of inhibition is postulated which involves the formation of a covalent bond between an enzyme nucleophile and a ketenimine formed from BAPN by enzyme-assisted beta-proton abstraction.
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PMID:Reaction of aortic lysyl oxidase with beta-aminopropionitrile. 613 92

Because high levels of dietary zinc are known to reduce copper body stores, the objective was to determine if a high zinc maternal diet could induce a copper deficiency in the newborn pig fed a dried skim milk--glucose--starch diet unsupplemented with copper. The offspring of gilts, which were fed 5000 ppm of zinc, were allowed to nurse until 3 to 5 days of age when they were weaned and placed in individual stainless-steel pens. The dietary treatments were 0, 5 and 10 ppm added copper from copper sulfate. After 14 days, pigs receiving the 0-ppm copper diet weighed significantly less (P less than 0.05) and had reduced hemoglobin, hematocrit and serum copper concentrations and no detectable ceruloplasmin activity. After 5 weeks, the pigs were killed, and tissues were collected. The unsupplemented group had 16.4% of the aortic lysyl oxidase activity of the 5-ppm group. Cytochrome c oxidase activity in the heart and liver, and copper stores in the heart, liver, pancreas and kidney were depressed (P less than 0.05) in unsupplemented pigs compared to those receiving 5 ppm copper. These data demonstrate that it is possible to produce quickly a markedly copper-deficient pig, by using the offspring of sows fed 5000 ppm zinc, and support previous conclusions that the dietary copper requirement of the baby pig is about 5 ppm.
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PMID:A copper deficiency in neonatal pigs induced by a high zinc maternal diet. 613 53

Small amounts of (+)-catechin (5 mg/kg body wt) administered intramuscularly to 8-day-old chicks raised the lysyl oxidase activity in aorta about 20%. (+)-Catechin had no effect on chicks that were copper-deficient. In the deficient chicks, (+)-catechin treatment prompted a substantially stronger increase in lysyl oxidase activity in response to CuSO4. The observed increments in lysyl oxidase activity in vivo were sensitive to inhibition by beta-aminopropionitrile (BAPN), suggesting that (+)-catechin was affecting the enzyme. (+)-Catechin in the assay medium partially inhibited lysyl oxidase activity. With excess copper ions present, (+)-catechin catalyzed a very strong release of volatile tritium from the substrate proteins. The release of tritium, indicative of lysyl oxidase activity, was not blocked by BAPN, suggesting that the activity in vitro was not enzyme catalyzed.
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PMID:Evaluation of (+)-catechin action on lysyl oxidase activity in aortic tissue. 613 26


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