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)

In the previous paper [ramos, S., and Kaback, H.R. (1977), Biochemistry 16 (preceding paper in this issue)], it was demonstrated that Escherichia coli membrane vesicles generate a large electrochemical proton gradient (delta-muH+) under appropriate conditions, and some of the properties of delta-muH+ and its component forces [i.e., the membrane potential (delta psi) and the chemical gradient of protons (deltapH)] were described. In this paper, the relationship between delta-muH+, delta psi, and deltapH and the active transport of specific solutes is examined. Addition of lactose or glucose 6-phosphate to membrane vesicles containing the appropriate transport systems results in partial collapse of deltapH, providing direct evidence for the suggestion that respiratory energy can drive active transport via the pH gradient across the membrane. Titration studies with valinomycin and nigericin lead to the conclusion that, at pH 5.5, there are two general classes of transport systems: those that are driven primarily by delta-muH+ (lactose, proline, serine, glycine, tyrosine, glutamate, leucine, lysine, cysteine, and succinate) and those that are driven primarily by deltapH (glucose 6-phosphate, D-lactate, glucuronate, and gluconate). Importantly, however, it is also demonstrated that at pH 7.5, all of these transport systems are driven by delta psi which comprises the only component of delta-muH+ at this external pH. In addition, the effect of external pH on the steady-state levels of accumulation of different solutes is examined, and it is shown that none of the pH profiles correspond to those observed for delta-muH+, delta psi, or deltapH. Moreover, at external pH values above 6.0-6.5, delta-muH+ is insufficient to account for the concentration gradients established for each substrate unless the stoichiometry between protons and accumulated solutes is greater than unity. The results confirm many facets of the chemiosmotic hypothesis, but they also extend the concept in certain important respects and allow explanations for some earlier observations which seemed to preclude the involvement of chemiosmotic phenomena in active transport.
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PMID:The relationship between the electrochemical proton gradient and active transport in Escherichia coli membrane vesicles. 1 65

The ras oncogene products (ras p21s) are 21-KDa proteins with activities of GTP binding and hydrolysis. A number of proteins homologous to ras p21 have been discovered and collectively named small molecular weight GTP-binding proteins. These proteins undergo post-translational modification with isoprenoid residues attached to cysteine in their carboxyl terminal. With this modification, they attach to cellular membranes. The biochemical activities of these proteins, i.e., GTP hydrolysis and binding, are regulated by various regulatory factors such as GDP-GTP exchange proteins and GTPase-activating proteins, but little is known about the cellular functions and physiological pathways through which they regulate these functions. Botulinum C3 ADP-ribosyltransferase, a 23-KDa exoenzyme secreted from certain strains of types C and D Clostridium botulinum, specifically ADP-ribosylates the rho family of these GTP-binding proteins. This ADP-ribosylation occurs at a specific asparagine residue in their putative effector domain, and presumably interferes with their interaction with a putative effector molecule downstream in signal transduction. C3 exoenzyme, when incubated with or microinjected into cultured cells, ADP-ribosylates a rho gene product in the cells, and causes profound cell rounding with loss of adhesion plaques and collapse of stress fiber. Microinjection of an activated mutant of rho A protein, on the contrary, induced extensive adhesion and actin assembly in cultured cells. These results suggest that the rho family of proteins are involved in morphogenesis and motility of cells via assembly and disassembly of cytoskeletal systems, and botulinum ADP-ribosyltransferase is a useful tool for clarifying the molecular mechanism of these processes.
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PMID:[ras oncogene-related small molecular weight GTP-binding protein, rho gene product and botulinum C3 ADP-ribosyltransferase]. 160 29

The chemical and kinetic mechanisms of purified aspartate-beta-semialdehyde dehydrogenase from Escherichia coli have been determined. The kinetic mechanism of the enzyme, determined from initial velocity, product and dead end inhibition studies, is a random preferred order sequential mechanism. For the reaction examined in the phosphorylating direction L-aspartate-beta-semialdehyde binds preferentially to the E-NADP-Pi complex, and there is random release of the products L-beta-aspartyl phosphate and NADPH. Substrate inhibition is displayed by both Pi and NADP. Inhibition patterns versus the other substrates suggest that Pi inhibits by binding to the phosphate subsite in the NADP binding site, and the substrate inhibition by NADP results from the formation of a dead end E-beta-aspartyl phosphate-NADP complex. The chemical mechanism of the enzyme has been examined by pH profile and chemical modification studies. The proposed mechanism involves the attack of an active site cysteine sulfhydryl on the carbonyl carbon of aspartate-beta-semialdehyde, with general acid assistance by an enzyme lysine amino group. The resulting thiohemiacetal is oxidized by NADP to a thioester, with subsequent attack by the dianion of enzyme bound phosphate. The collapse of the resulting tetrahedral intermediate leads to the acyl-phosphate product and liberation of the active site cysteine.
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PMID:Chemical and kinetic mechanisms of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli. 167 60

1. Values of the kinetic specificity constant, kcat./Km, for the hydrolysis of N-acetyl-L-phenylalanylglycine 4-nitroanilide (I) and of its D-enantiomer (II) catalysed by ficin (EC 3.4.22.3) and by actinidin (EC 3.4.22.14) at pH 6.0, I 0.1 mol/l, 8.3% (v/v) NN-dimethylformamide and 25 degrees C were determined by using initial-rate data with [S] much less than Km and weighted nonlinear regression analysis as: for ficin, (kcat./Km)L = 271 +/- 6 M-1.s-1, (kcat./Km)D = 2.9 +/- 0.1 M-1.s-1, and for actinidin (kcat./Km)L = 13.3 +/- 0.7 M-1.s-1, (kcat/Km)D = 0.34 +/- 0.01 M-1.s-1.2. These data and analogous values for the corresponding reactions catalysed by papain (EC 3.4.22.2), (kcat./Km)L = 2064 +/- 31 M-1.s-1, (kcat./Km)D = 5.5 +/- 0.1 M-1.s-1, demonstrate marked variation in stereochemical selectivity for substrates (I) and (II) among the three cysteine proteinases with the following values for the index of stereochemical selectivity Iss = (kcat./Km)L/(kcat./Km)D: for papain, 375; for ficin 93; for actinidin 39. 3. Model building suggests ways in which, for the papain-catalysed reactions, binding interactions involving the extended acyl groups of the substrates may need to change as the reaction proceeds from adsorptive complex (ES) to tetrahedral intermediate (THI) before its rate-determining, general acid-catalysed collapse to acylenzyme intermediate. In particular, satisfactory alignment in the catalytic site at the THI stage of the acylation process appears to demand rotation of the substrate moiety about its long axis. 4. The different consequences of this rotation for the L- and D-enantiomers suggest that for closely related systems the greater the extent of this rotational adjustment the greater would be the value of Iss.5. For the actinidin-substrate combinations, model building suggests that even at the ES complex stage of catalysis it is not possible to approach optimized P2-S2 contacts and the three hydrogen-bonding interactions deduced for papain-ligand complexes in the absence of significant movement of protein conformation. Possible binding modes in which some of the interactions deduced for papain are relaxed are discussed. Consideration of postulated binding modes in the various transition states is shown to account for the order of reactivity reflected in values kcat./Km for the four reactions involving papain (Pap) and actinidin (Act) with the L- and D-enantiomeric substrates: Pap-L much greater than Act-L greater than Pap-D much greater than Act-D.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Variation in the P2-S2 stereochemical selectivity towards the enantiomeric N-acetylphenylalanylglycine 4-nitroanilides among the cysteine proteinases papain, ficin and actinidin. 173 3

Rhabdomeres of tipulid flies lose membrane during turnover from a 'shedding zone' composed of microvillar tips. These distal domains lack intramicrovillar cytoskeletons and appear to be empty sacs of membrane. Recent concerns about the role of ninaC mechano-enzymes in the architecture of dipteran rhabdomeral microvilli and the dynamic role that they may play in the creation of shedding zones demand an examination of the distribution of actin in tipulid rhabdomeres. We compared rhabdomeres from tipulid retinae incubated before fixation for immunocytochemistry in a buffer without additives and a stabilising buffer that contained a cocktail of cysteine protease inhibitors; both were challenged by an anti-actin antibody for immunogold labelling after embedding in LR White Resin. Shedding zones thus processed collapse to structureless detritus. Stabilised and unstabilized shedding zones were immunonegative to anti-actin. To ensure that the negative results were not consequent upon conformational changes generated by the processing protocol, we examined microvilli of degenerating rhabdomeres of the Drosophila light-dependent retinal degeneration mutant rdgBKS222 (which separate and collapse without creating a shedding zone) and found the detritus they generate to be immunopositive to anti-actin. Stabilised and unstabilized regions of basal regions of tipulid rhabdomeres were equally immunopositive. We infer that (a) actin is absent from shedding zones; (b) actin is not degraded by microvillar cysteine proteases. The implications of these conclusions are discussed in relation to some functional models of arthropod photoreceptor microvilli.
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PMID:The distribution of actin immunoreactivity in rhabdomeres of tipulid flies in relation to extracellular membrane shedding. 178 93

Pulmonary surfactant prevents collapse of lung alveoli by lowering surface tension at the air/liquid interface. The hydrophobic surfactant associated proteins SP-B and SP-C have been shown to be important in surfactant function and metabolism. A cDNA clone for rat SP-B was isolated and sequenced. Northern analysis showed mRNA for SP-B was present in whole lung and was greatly enriched in alveolar type II cells, but was not present in brain, kidney, spleen or liver. A full length transcript of the rat SP-B cDNA clone consists of 1536 bases and encodes an open reading frame of 376 amino acids. The predicted molecular mass of the primary translation product is 42 kDa and the predicted molecular mass of the mature protein is 8 kDa. Extensive homology exists between the rat sequence for SP-B and those reported for human and canine SP-B. The position of 25 cysteine residues has been extremely well preserved across all three species. An N-linked glycosylation site in the COOH region has been conserved across all three species. A search of the NIH database revealed homology between rat SP-B and the active site for the mouse contrapsin serum proteinase inhibitor.
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PMID:cDNA and deduced amino acid sequence for the rat hydrophobic pulmonary surfactant-associated protein, SP-B. 292 Jan 85

The surgical repair of subglottic stenosis (SGS) is often unsuccessful because of recurrence of the scar contracture. Over the past few years, two lathyrogenic agents (compounds that inhibit collagen cross-linking) have been shown effective in prevention of stenosis in animal models that have deep caustic esophageal burns. Since the principles of induced lathyrism have not been applied to the treatment of laryngotracheal stenosis, a pilot study using a canine model was conducted to test the efficacy of penicillamine and N-acetyl-L-cysteine in reduction of the rate of reformation of SGS. In all six animals used, a complete, 10 to 15 mm thick, mature SGS was induced experimentally, then opened with a CO2 laser. The dogs that were treated with lathyrogenic agents exhibited a lower rate of re-stenosis (one maintained patency throughout the 5 weeks of treatment) when compared to the two control dogs. Histologic sections of the subglottis in each dog revealed severe cricoid collapse, necrosis, and scarring, and thus demonstrated similarities to SGS in human beings. The two lathyrogenic agents used in this study are already approved for human use and may represent a valuable form of adjunctive therapy in the surgical management of SGS.
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PMID:Lathyrogenic agents as therapy for subglottic stenosis--a pilot study. 312 Jan 20

Using a mucolytic agent, N-acetyl-L-cysteine (NAC), the structure of rat gastric mucous glycoprotein (GP) and its participation in prostaglandin cytoprotection were studied. Treatment of the undegraded native mucous GP with 20% NAC resulted in a marked reduction in molecular weight as obtained in the case of treatment with 0.5 M beta-mercaptoethanol. The amount of GP remaining in the gastric tissue, including the mucous layer after 3 h-incubation was defined as an indication of the mucous adhesiveness to the gastric mucosal surface. The adhesiveness was markedly decreased by the in vitro or in vivo treatment with NAC. The cytoprotective effect of prostaglandin E2 was significantly reduced by pretreatment with NAC. Elution profiles of mucous GP on Sepharose CL-2B showed a good correlation between decrease in the amount of the undegraded native mucous GP and the severity of gastric damage. In addition, the collapse of the native mucous GP into its subunits resulted in a decrease in the adhesiveness. These observations suggest that the maintenance of the native mucous GP is an essential factor for prostaglandin cytoprotection.
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PMID:Changes in the structure of rat mucous glycoprotein and prostaglandin cytoprotection. 346 64

The subcellular mechanism of alkenyl halide S-conjugate-induced nephrotoxicity was studied in mitochondria isolated from rat kidney cortex in vitro using the cysteine conjugate of hexachloro-1,3-butadiene, i.e., S-pentachlorobutadienyl-L-cysteine (PCBC) as a model substrate. Respiring mitochondria exposed to various concentrations of PCBC exhibited a dose-dependent loss of ability to retain calcium. This phenomenon was associated with a sudden collapse of the mitochondrial membrane potential. PCBC caused a slow nonenzymatic depletion of mitochondrial glutathione. This was not due to oxidation or formation of mixed disulfides, and was efficiently counteracted by preincubation with aminooxyacetic acid, an inhibitor of cysteine-conjugate beta-lyase activity. PCBC inhibited state 3 respiration in the presence of succinate as substrate, which indicates that the activity of succinate dehydrogenase was affected. Thus, the present data confirm that impairment of mitochondrial function is a feature of nephrotoxicity mediated by alkenyl halide S-conjugates. We suggest a pathway involving interaction of beta-lyase-dependent reactive metabolite with the mitochondrial inner membrane, loss of membrane potential, disturbance of Ca2+ homeostasis, and subsequent respiratory insufficiency as a mechanism for renal tubular cytotoxicity.
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PMID:Toxicity of S-pentachlorobutadienyl-L-cysteine studied with isolated rat renal cortical mitochondria. 367 80

Studies on the activation and excystation of I. felis and I. rivolta sporozoites revealed that, although some differences were apparent between the two, both were capable of activation under a wide range of conditions. Activation of both species took place in trypsin and bile between 21 and 43 C (the range tested) occurring rapidly at 39 C. Although the presence of bile appeared to be essential for this process that of trypsin did not. Neither the concentration of bile (above 5%), the type of bile, nor the hydrogen ion concentration had a marked effect on the level of activation. Pretreatment of oocysts in aqueous cysteine hydrochloride under CO2 or with sodium hypochlorite before exposure to trypsin and bile was not an essential prerequisite for the activation of I. felis and I. rivolta. However, higher levels of activation were attained when pretreatment was used. But for I. rivolta, the level of activation appeared to be less dependent on pretreatment for oocysts stored in sulfuric acid than for those stored in potassium dichromate. The process of activation and excystation of both species was essentially similar to that described for other species of disporocystic coccidia with heteroxenous life cycles. Sporozoites escaped following the collapse of the sporocyst wall and completed excystation through indentations and fractures at one or both ends of the oocyst.
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PMID:Activation and excystation of Isospora felis and Isospora rivolta sporozoites. 707 58


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