Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Presented is the case of a 62-year-old man with refractory shock secondary to copper sulfate ingestion. The patient's history was complicated by the presence of peptic ulcer disease, myocardial disease, and a known abdominal aortic aneurysm. Despite the presence of such characteristic signs and symptoms as hemorrhagic gastroenteritis, hemolytic anemia, and refractory hypotension, the diagnosis of copper sulfate ingestion was delayed for several days after ingestion, when the family first volunteered that the patient had vomited blue-green material the day before his admission to the hospital. This delay contributed significantly to the patient's ultimate demise.
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PMID:Refractory shock secondary to copper sulfate ingestion. 374 May 85

A spontaneously aneurysm-prone mouse has a mutation on the X chromosome, which results in an abnormality of copper metabolism. A deficiency of the copper metalloenzyme, lysyl oxidase, results in a deficiency of lysyl-derived cross-linkages in collagen and elastin. Homology of the X chromosome suggests that this model may be relevant to the human abdominal aortic aneurysm (AAA). The present studies on skin from eight AAA patients suggest that copper deficiency occurs in humans, by comparison to skin of paired control subjects with atherosclerotic occlusive disease of the aorta. The lysyl-derived cross-linkage pyridinoline (or some compound with similar ion exchange elution characteristics) is also deficient in patients with AAA; while there is an excess of one of the cross-linkage precursors, hydroxylysine. In addition, the fluorescent properties of hydrolysates of skin from the patients with AAA differ from those of the controls, suggesting that simple biochemical markers might be defined on the basis of these differences in the future. These experiments support the hypothesis that the mouse model is relevant to the disease as it occurs in humans.
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PMID:Deficiencies of copper and a compound with ion-exchange characteristics of pyridinoline in skin from patients with abdominal aortic aneurysms. 687 35

Changes in copper concentration in the arterial wall are important because of cross-linkage formation in collagen and elastin. The breakdown of the elastic layer is characteristic for aneurysm and is affected by the abnormalities in copper metabolism. This study was undertaken to evaluate Ca, Mg, Zn and Cu concentrations and their relationships in the arterial wall, serum and calcified plaque in atherosclerosis obliterans (AO) and abdominal aortic aneurysm (AA). Samples of the aorta wall were obtained at the endarterectomy in AO and the vascular reconstruction in AA. Elements were determined by means of atomic absorption spectrometry. Serum concentrations of Zn and Cu were higher and that of Ca lower in AO as compared to AA and the controls. Arterial concentrations of Zn, Cu and Mg were higher in AO as compared to AA. The ratios of element concentrations in serum (Ca/Mg, Ca/Zn and Mg/Cu) were higher in serum in AA than in AO. Positive correlations were calculated for Ca and Mg (r > or = 0.74), Ca and Zn (r > or = 0.73), Mg and Zn (r > or = 0.90) in the arterial wall in AO and AA. Low but significant correlation was calculated for Cu concentrations between serum and the arterial wall in AA (r = 0.43). Concentrations of Ca, Mg, Zn and Cu were higher in plaque than in the surrounding tissue. The results indicate differences in arterial and serum concentrations of Ca, Mg, Zn and Cu between AO and AA and the accumulation of these elements in the plaque rather than in the surrounding vascular tissue.
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PMID:Relationship of calcium, magnesium, zinc and copper concentrations in the arterial wall and serum in atherosclerosis obliterans and aneurysm. 957 76

Although the body status of zinc and copper in cardiovascular disease (CVD) has been shown to be important little is known about the effect of these trace element alterations on lipolytic enzyme activities in atherosclerosis human subjects. The aim of the present study was to evaluate the multiple relationships between lipase (GEH = glycerol ester hydrolase, EC 3.1.1.3) activity, zinc, copper and lipid concentrations in serum and the arterial wall of men with atherosclerosis obliterans (AO) and abdominal aortic aneurysm (AA). The mean concentrations of zinc and copper in serum were found to be higher in AO in comparison to AA. Low but significant correlation coefficients for zinc and lipase catalytic activity (r > or = 0.64) and lipase metabolic activity GEH/TAG (r > or = 0.67) were calculated in serum in AA. Multiple correlation coefficients (R) for three variables GEH-Zn-Cu were found to be significant for both AO and AA (R > or = 0.45 and 0.68, respectively) in serum but not in the arterial wall. Multiple relations for GEH/TAG-HDL-C (LDLC)-Zn(Cu) were found to be significant (R > or = 0.63) in serum in AA. The results indicate the influence of zinc and copper on the activity of lipase and lipid concentrations and suggest that the multiple relations may provide a better understanding of the role these elements play in atherosclerosis than relations between 2 substances.
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PMID:Serum glycerol ester hydrolase activity is related to zinc and copper concentrations in atherosclerosis obliterans and aneurysm. 963 11

In mammalian cells, mitochondria provide energy from aerobic metabolism. They play an important regulatory role in apoptosis, produce and detoxify free radicals, and serve as a cellular calcium buffer. Neurodegenerative disorders involving mitochondria can be divided into those caused by oxidative phosphorylation (OXPHOS) abnormalities either due to mitochondrial DNA (mtDNA) abnormalities, e.g., chronic external ophthalmoplegia, or due to nuclear mutations of OXPHOS proteins, e.g., complex I and II associated with Leigh syndrome. There are diseases caused by nuclear genes encoding non-OXPHOS mitochondrial proteins, such as frataxin in Friedreich ataxia (which is likely to play an important role in mitochondrial-cytosolic iron cycling), paraplegin (possibly a mitochondrial ATP-dependent zinc metalloprotease of the AAA-ATPases in hereditary spastic paraparesis), and possibly Wilson disease protein (an abnormal copper transporting ATP-dependent P-type ATPase associated with Wilson disease). Huntingon disease is an example of diseases with OXPHOS defects associated with mutations of nuclear genes encoding non-mitochondrial proteins such as huntingtin. There are also disorders with evidence of mitochondrial involvement that cannot as yet be assigned. These include Parkinson disease (where a complex I defect is described and free radicals are generated from dopamine metabolism), amyotrophic lateral sclerosis, and Alzheimer disease, where there is evidence to suggest mitochondrial involvement perhaps secondary to other abnormalities.
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PMID:Mitochondria and degenerative disorders. 1157 22

New classes of nucleophiles, pyrroles, and N-methoxyamides were developed for Pd-catalyzed AAA reactions. By varying the functional groups at the 2-position of pyrroles, either regioisomer of the piperazinone is available. Using one regioisomer, the total synthesis of (+)-agelastatin A in 10 total steps is accomplished. For this synthesis, a new copper-catalyzed aziridination and an indium-catalyzed oxidative ring opening of a N-tosylaziridine were developed. The feasibility of accessing (-)-agelastatin A from the same enantiomer of the chiral catalyst from the other regioisomeric piperazinone is indicated.
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PMID:New class of nucleophiles for palladium-catalyzed asymmetric allylic alkylation. Total synthesis of agelastatin A. 1666 72

In this article, we report a full account of our recent development of pyrroles and N-alkoxyamides as new classes of nucleophiles for palladium-catalyzed AAA reactions, along with application of these methodologies in the total synthesis of agelastatin A, a marine natural product with exceptional anticancer activity and other biological properties. Our method allows for access to either regioisomer of the pyrrolopiperazinones (6 and 19) with high efficiency and enantioselectivity. Note that isomer 19 was obtained via a cascade reaction through a double allylic alkylation pathway. From regioisomer 6, the total synthesis of (+)-agelastatin A was completed in a very short fashion (four steps from 6), during the course of which we developed a new copper catalyst for aziridination and an In(OTf)(3)/DMSO system to oxidatively open an N-tosyl aziridine. Starting with the other pyrrolopiperazinone 19, a five-step sequence has been developed to furnish a formal total synthesis of (-)-agelastatin A. A unique feature of our syntheses is the use of two rather different strategies for the total syntheses of both enantiomers of agelastatin A using the same enantiomer of a chiral palladium catalyst.
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PMID:A stereodivergent strategy to both product enantiomers from the same enantiomer of a stereoinducing catalyst: agelastatin A. 1953 7

Archaea such as Metallosphaera sedula are thermophilic lithoautotrophs that occupy unusually acidic and metal-rich environments. These traits are thought to underlie their industrial importance for bioleaching of base and precious metals. In this study, a genetic approach was taken to investigate the specific relationship between metal resistance and lithoautotrophy during biotransformation of the primary copper ore, chalcopyrite (CuFeS(2)). In this study, a genetic system was developed for M. sedula to investigate parameters that limit bioleaching of chalcopyrite. The functional role of the M. sedula copRTA operon was demonstrated by cross-species complementation of a copper-sensitive Sulfolobus solfataricus copR mutant. Inactivation of the gene encoding the M. sedula copper efflux protein, copA, using targeted recombination compromised metal resistance and eliminated chalcopyrite bioleaching. In contrast, a spontaneous M. sedula mutant (CuR1) with elevated metal resistance transformed chalcopyrite at an accelerated rate without affecting chemoheterotrophic growth. Proteomic analysis of CuR1 identified pleiotropic changes, including altered abundance of transport proteins having AAA-ATPase motifs. Addition of the insoluble carbonate mineral witherite (BaCO(3)) further stimulated chalcopyrite lithotrophy, indicating that carbon was a limiting factor. Since both mineral types were actively colonized, enhanced metal leaching may arise from the cooperative exchange of energy and carbon between surface-adhered populations. Genetic approaches provide a new means of improving the efficiency of metal bioleaching by enhancing the mechanistic understanding of thermophilic lithoautotrophy.
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PMID:Metal resistance and lithoautotrophy in the extreme thermoacidophile Metallosphaera sedula. 2306 78

Human copper transporter 1 (hCTR1) is a homotrimer of a 190-amino acid monomer having three transmembrane domains believed to form a pore for copper permeation through the plasma membrane. The hCTR1-mediated copper transport mechanism is not well understood, nor has any measurement been made of the rate at which copper ions are transported by hCTR1. In this study, we estimated the rate of copper transport by the hCTR1 trimer in cultured cells using (64)Cu uptake assays and quantification of plasma membrane hCTR1. For endogenous hCTR1, we estimated a turnover number of about 10 ions/trimer/s. When overexpressed in HEK293 cells, a second transmembrane domain mutant of hCTR1 (H139R) had a 3-fold higher Km value and a 4-fold higher turnover number than WT. Truncations of the intracellular C-terminal tail and an AAA substitution of the putative metal-binding HCH C-terminal tripeptide (thought to be required for transport) also exhibited elevated transport rates and Km values when compared with WT hCTR1. Unlike WT hCTR1, H139R and the C-terminal mutants did not undergo regulatory endocytosis in elevated copper. hCTR1 mutants combining methionine substitutions that block transport (M150L,M154L) on the extracellular side of the pore and the high transport H139R or AAA intracellular side mutations exhibited the blocked transport of M150L,M154L, confirming that Cu(+) first interacts with the methionines during permeation. Our results show that hCTR1 elements on the intracellular side of the hCTR1 pore, including the carboxyl tail, are not essential for permeation, but serve to regulate the rate of copper entry.
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PMID:Rate and regulation of copper transport by human copper transporter 1 (hCTR1). 2365 18

FeaR is an AraC family regulator that activates transcription of the tynA and feaB genes in Escherichia coli. TynA is a periplasmic topaquinone- and copper-containing amine oxidase, and FeaB is a cytosolic NAD-linked aldehyde dehydrogenase. Phenylethylamine, tyramine, and dopamine are oxidized by TynA to the corresponding aldehydes, releasing one equivalent of H2O2 and NH3. The aldehydes can be oxidized to carboxylic acids by FeaB, and (in the case of phenylacetate) can be further degraded to enter central metabolism. Thus, phenylethylamine can be used as a carbon and nitrogen source, while tyramine and dopamine can be used only as sources of nitrogen. Using genetic, biochemical and computational approaches, we show that the FeaR binding site is a TGNCA-N8-AAA motif that occurs in 2 copies in the tynA and feaB promoters. We show that the coactivator for FeaR is the product rather than the substrate of the TynA reaction. The feaR gene is upregulated by carbon or nitrogen limitation, which we propose reflects regulation of feaR by the cyclic AMP receptor protein (CRP) and the nitrogen assimilation control protein (NAC), respectively. In carbon-limited cells grown in the presence of a TynA substrate, tynA and feaB are induced, whereas in nitrogen-limited cells, only the tynA promoter is induced. We propose that tynA and feaB expression is finely tuned to provide the FeaB activity that is required for carbon source utilization and the TynA activity required for nitrogen and carbon source utilization.
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PMID:Finely tuned regulation of the aromatic amine degradation pathway in Escherichia coli. 2401 33


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