Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel method for the synthesis of methyl dialkylmalonuric esters was developed using the base-catalyzed ring opening of an isopropylidene malonic ester with urea as the key step. The rates of cyclization of these malonuric esters to the corresponding barbituric acids then were studied at buffer concentrations ranging from 0.01 to 1.00 M. The reaction was shown to be general base catalyzed, and the reaction rate was found to be subject to a deuterium isotope effect, kH2O/kD2O=1.3. The thermodynamic activation parameters also were determined. A three-step mechanism for the conversion of malonuric esters to barbituric acids was proposed; it involved a rapid cyclization step, followed by proton removal by a general base catalyst and a rate-determining collapse of the resulting tetrahedral intermediate aided by a general acid.
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PMID:Synthesis and cyclization of dialkylmalonuric esters. 737 43

To assess the role of hemofiltration (HF) among different treatment modalities, we reviewed our clinical material from 37 patients that consecutively underwent the treatment from 1981 on. A number of 12 patients on HF for at least 1 year deliberately switched to hemodialysis (HD) or hemodiafiltration (HDF) were studied retrospectively. Biochemical and nutritional parameters, cardiovascular aspects and morbidity data were collected during one year before and after the treatment change. A sodium balance study was performed in 9 patients during HF as well. No significant differences in plasma urea, creatinine, phosphate, body weight, serum albumin, transferrin, hemoglobin and PCR were found. BUN tended to be lower during HD-HDF because of the more efficient removal of urea with these treatments. Indeed, the Kt/V index was 0.91 during HF and it was 1.15 with HD-HDF. There were no differences in hypotensive episodes and morbidity. Sodium loss was strictly related to body fluid removal during HF session with a net sodium loss (NSL) of 128 mEq per liter of fluid removal (FR) (NSL = 6.44 + 122 FR; r:0.83; p < 0.01). Adapting sodium concentration of substitution fluid to patients weight gain, cardiovascular stability improved in those subjects more prone to collapse. With equivalence in PCR during the 2 periods, although Kt/V was 20% lower during HF, it seems reasonable to assume that the lower urea clearance might be compensated by the more efficient removal of higher molecular weight substances and/or by the improved biocompatibility of HF.
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PMID:The contribution of hemofiltration among the treatment modalities of chronic uremia. 817 95

Using three different trans dominant mutants of bovine ARF1 affecting GDP exchange or GTP hydrolysis we demonstrate the central role of ARF1 in controlling vesicular traffic from the endoplasmic reticulum (ER) to the Golgi apparatus and between successive Golgi compartments. Overexpression of ARF1(Q71L), a mutant likely to be restricted to the GTP-bound form, resulted in the accumulation of vesicular stomatitis virus glycoprotein in pre-Golgi intermediates, inhibited transport between successive Golgi compartments, and led to a striking association of beta-COP with pre-Golgi intermediates and the Golgi stack. In contrast, ARF1(T31N), a mutant which is likely to have a preferential affinity for GDP compared to the wild-type protein, inhibited export from the ER and triggered a brefeldin A-like phenotype, resulting in the redistribution of beta-COP from Golgi membranes to the cytosol and the collapse of the Golgi into the ER. This mutant, which may efficiently sequester an ARF-specific guanine nucleotide-exchange protein (ARF-GEF), suggests that ARF and ARF-GEF are essential for export from the ER. These results are discussed in the context of the GDP and GTP-bound forms of ARF in controlling both membrane structure and vesicular traffic through the early secretory pathway.
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PMID:Dominant inhibitory mutants of ARF1 block endoplasmic reticulum to Golgi transport and trigger disassembly of the Golgi apparatus. 828 10

How important are helical propensities in determining the conformations of globular proteins? Using the two-dimensional lattice model and two monomer types, H (hydrophobic) and P (polar), we explore both nonlocal interactions, through an HH contact energy, epsilon, as developed in earlier work, and local interactions, through a helix energy, sigma. By computer enumeration, the partition functions for short chains are obtained without approximation for the full range of both types of energy. When nonlocal interactions dominate, some sequences undergo coil-globule collapse to a unique native structure. When local interactions dominate, all sequences undergo helix-coil transitions. For two different conformational properties, the closest correspondence between the lattice model and proteins in the Protein Data Bank is obtained if the model local interactions are made small compared to the HH contact interaction, suggesting that helical propensities may be only weak determinants of globular protein structures in water. For some HP sequences, varying sigma/epsilon leads to additional sharp transitions (sometimes several) and to "conformational switching" between unique conformations. This behavior resembles the transitions of globular proteins in water to helical states in alcohols. In particular, comparison with experiments shows that whereas urea as a denaturant is best modeled as weakening both local and nonlocal interactions, trifluoro-ethanol is best modeled as mainly weakening HH interactions and slightly enhancing local helical interactions.
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PMID:Local and nonlocal interactions in globular proteins and mechanisms of alcohol denaturation. 829 55

Specific three- and two-disulfide intermediates that accumulate transiently during reduction of the disulfide bonds of Ca(2+)-bound bovine alpha-lactalbumin have been trapped, isolated, and characterized. The three-disulfide intermediate was shown to lack the Cys6-120 disulfide bond, confirming the observations of others. The newly-recognized two-disulfide form has been shown to lack the Cys6-120 and Cys28-111 native disulfide bonds. The remaining native disulfide bonds in the two partially reduced derivatives of alpha-lactalbumin are stable only when the proteins are in a Ca(2+)-bound state. Otherwise, they adopt an equilibrium between molten globule and unfolded conformations, and rapid thiol-disulfide interchange occurs, at a rate as high as when the proteins are fully unfolded in 8 M urea, to generate distinct mixtures of rearranged products. Urea gradient electrophoresis, circular dichroism, fluorescence, and ANS binding have been combined to give a detailed structural picture of alpha-lactalbumin, its derivatives with native and with nonnative disulfide bonds, and the fully reduced protein. The native structure of alpha-lactalbumin appears to be split by selective disulfide bond cleavage into at least one subdomain, which retains the Ca(2+)-binding site. The alpha-lactalbumin molten globule state is shown largely to result from nonspecific hydrophobic collapse, to be devoid of cooperative or specific tertiary interactions, and not to be stabilized substantially by the native or rearranged disulfide bonds.
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PMID:Structural characterization of the disulfide folding intermediates of bovine alpha-lactalbumin. 846 9

Unfolding and refolding of plasma vitronectin appear irreversible under near physiological conditions, with rearrangements of disulfides and self-association to a multimeric form observed as prominent structural alterations which accompany denaturation. A mechanism for the folding reactions of vitronectin has been proposed (Zhuang, P., Blackburn, M. N., and Peterson, C. B.(1996) J. Biol. Chem. 270, 14323-14332) in which vitronectin acquires a partially folded intermediate structure which is highly prone to oligomerize into a multimeric form. Strongly oxidizing conditions adopted for refolding from urea were effective at preventing disulfide rearrangement which disrupts distal disulfides near the C terminus of the protein. Prohibiting disulfide rearrangement under these conditions, however, was not sufficient to achieve reversibility in folding. In contrast, variations in the ionic strength of the refolding medium affect the partitioning of species so that refolded monomers are obtained at high ionic strength, and self-association is precluded. The effects of ionic strength on the partially folded intermediate in the vitronectin folding pathway appear to favor intramolecular hydrophobic collapse to form a stable hydrophobic core for the monomer versus intermolecular hydrophobic interactions which stabilize multimeric vitronectin. Although both ionic and hydrophobic interactions presumably contribute to subunit interfaces within the multimer, the basic heparin-binding region near the C terminus of the protein does not provide binding interactions which are important for self-association of vitronectin.
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PMID:Characterization of the denaturation and renaturation of human plasma vitronectin. II. Investigation into the mechanism of formation of multimers. 866 85

Between October 1979 and January 1993, 85 Chinese neonates in Hong Kong underwent surgical repair for coarctation of the aorta. Their mean (s.e.) age and body weight at operation was 15.6(8.5) days and 3.06(0.56) kg, respectively. Simple coarctation was present in 17 babies, while 36 had additional ventricular septal defect and 31 had associated major complex intracardiac lesions. Subclavian flap aortoplasty was performed in 56 babies, resection with end-to-end anastomosis in 18 and aortoplasty with the use of a GORETEX patch in 11. The overall early mortality rate was 16.5%. To identify risk factors for early operative mortality, various clinical variables, surgical options, associated heart lesions and dimensions of the aortic arch at different sites for each patient were reviewed. Univariate analysis identified statistically significant differences between the survivors and non-survivors for the following factors: preoperative body-weight, arterial pH and base excess, serum urea and creatinine levels. Stepwise logistic regression further distinguished serum creatinine levels and the period of operation as two significant risk factors. Contrary to previous reports, the dimensions of the aortic arch and type of surgery did not affect early operative mortality. Among the 71 hospital survivors followed for 38.2(38) months, residual or recurrent coarctation of the aorta was detected in 12(17%). The different surgical operations were not related to the incidence of late complication. The size of the distal transverse arch, however, was different (P=0.05) in those who did and did not develop aortic sequela. Successful balloon angioplasty was subsequently performed in 11 patients. In an era of echocardiography with prenatal diagnosis and therapeutic catheterization, early recognition of the disease with prompt prostaglandin infusion should prevent collapse of the baby, thus avoiding renal impairment and sever metabolic acidosis. Balloon angioplasty would offer a simple effective treatment of patients who developed aortic re-coarctation.
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PMID:Surgical repair of coarctation of the aorta in neonates: factors affecting early mortality and re-coarctation. 874 72

The folding-unfolding kinetics of human alpha 1-antitrypsin (alpha 1-AT) were examined by monitoring intrinsic Trp fluorescence and extrinsic ANS fluorescence. While the unfolding of alpha 1-AT followed a single exponential phase, refolding exhibited three exponential phases. The fast phase (tau 1r < 40 sec). which was independent of urea concentration, appears to be hydrophobic collapse that may be limited by cis-trans isomerization of prolyl residue. The medium phase (tau 2s = 200 sec) yielded an intermediate (IN), which is capable of elastase binding. The slowest (tau 3r = 1000 sec) phase completes refolding to the native protein, which intersects with the unfolding kinetics at the same urea concentration (1.9 M) as the equilibrium midpoint. Concentration-dependence of the amplitude of major refolding phases indicated that IN is prone to kinetic competition between the on-pathway to native protein and aggregation.
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PMID:Folding pathway of human alpha 1-antitrypsin: characterization of an intermediate that is active but prone to aggregation. 880 43

The mechanism of folding and membrane insertion of integral membrane proteins, including helix bundle and beta-barrel proteins is not well understood. A key question is whether folding and insertion are coupled or separable processes. We have used the beta-barrel outer membrane protein A (OmpA) of Escherichia coli as a model to study the kinetics of folding and insertion into dioleoylphosphatidylcholine (DOPC) bilayers, as a function of temperature by gel electrophoresis, protease digestion, and fluorescence spectroscopy. OmpA was unfolded in 8 M urea solution (without detergent), and refolding and membrane insertion was initiated by rapid dilution of the urea concentration in the presence of phospholipid vesicles. In addition to the kinetically unresolved hydrophobic collapse in water, the time course of refolding of OmpA into DOPC bilayers exhibited three kinetic phases over a large temperature range. The first step was fast (k1 = 0.16 min-1) and not very dependent on temperature. The second step was up to two orders of magnitude slower at low temperatures (2 degrees C), but approached the rate of the first step at higher temperatures (40 degrees C). The activation energy for this process was 46 +/- 4 kJ/mol. A third slow process (k3 = 0.9 x 10(-2) min-1 at 40 degrees C) was observed at the higher temperatures. These results suggest that at least two membrane-bound intermediates exist when OmpA folds and inserts into lipid bilayers. We also show that both membrane-bound intermediates can be stabilized in fluid lipid bilayers at low temperatures. These intermediates share many properties with the adsorbed/partially inserted form of OmpA that was previously characterized in gel phase lipid bilayers [Rodionova et al. (1995) Biochemistry 34, 1921-1929]. Temperature jump experiments demonstrate, that the low-temperature intermediates can be rapidly converted to fully inserted native OmpA. On the basis of these and previous results, we present a simple folding model for beta-barrel membrane proteins, in which folding and membrane insertion are coupled processes which involve at least four kinetically distinguishable steps.
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PMID:Folding intermediates of a beta-barrel membrane protein. Kinetic evidence for a multi-step membrane insertion mechanism. 885 33

In order to evaluate the role of underlying disease in the high mortality observed in acute renal failure (ARF) and risk factors related to the development of oliguric ARF in renal allograft recipients, two groups were selected: 34 patients with native kidneys, aged 16 and 57 years, and presenting ischemic ARF caused by cardiovascular collapse, with no signs of infection at the time of diagnosis; and 34 renal allograft recipients who developed ARF immediately after transplantation, without rejection. ARF was defined either as 30% increase of basal plasmatic creatinine in patients with native kidneys or nonnormalization of plasmatic creatinine at day 5 after transplantation in renal allograft recipients; oliguria as diuresis < or = 400 mL/24 h. There were no differences in age, male frequency, oliguria presence and duration, need for dialysis, and infection episodes for renal allograft recipients and patients with native kidneys. The development of sepsis (3% and 41%) and death rate (3% and 44%) were higher in patients with native kidneys (p < 0.01). The renal allograft recipients with both oliguric (n = 18) and nonoliguric (n = 16) ARF were evaluated and no difference was observed in the recipient's age, donor's age, cold ischemia time, time elapsed until plasmatic creatinine normalization, donor's plasmatic creatinine or urea, and mean arterial pressure. No differences were observed between the groups regarding frequency of infection episodes during ARF and frequency of death. In conclusion, renal allograft recipients presented a lower death rate and were less susceptible to sepsis. Cold ischemia time, age, and hemodynamic characteristics of the donor did not affect the development of oliguria.
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PMID:Acute renal failure in renal allograft recipients and patients with native kidneys. 910 1


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