Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Concentrations of dopamine, serotonin, and some of their metabolites were analyzed by means of HPLC in brain samples obtained from rats operantly conditioned to turn in circles to obtain water reinforcement. In experiment 1 using Wistar rats, no differences in the levels of transmitters or metabolites were detected between brain samples (frontal cortex, ventral striatum, dorsal striatum, septum, amygdala, substantia nigra) from the hemispheres located ipsi- and contralateral to the direction of turning. A higher dopamine metabolism (indicated by higher metabolite/transmitter ratios) in ventral striatum, dorsal striatum, and amygdala was found after 15 min than after 5 min of turning in both hemispheres. A higher dopamine metabolism was found in water-deprived rats compared to nondeprived rats independently of whether or not deprived rats were trained to turn for water reinforcement. In two additional experiments, no differences in dopamine metabolism were found between the ipsi- and contralateral striatum of Wistar rats after 25 min and Sprague-Dawley rats after 10 min of operantly conditioned turning. The present results confirm that dopamine metabolism can change with different behavioral or physiological states; they do not support the hypothesis that conditioned turning is correlated with asymmetrical changes in the metabolism of dopamine or serotonin in the brain.
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PMID:Dopamine and serotonin metabolism in brain sites ipsi- and contralateral to direction of conditioned turning in rats. 355 61

The crystal structure of a daunomycin-d(CGTACG) complex has been solved by X-ray diffraction analysis and refined to a final R factor of 0.175 at 1.2-A resolution. The crystals are in a tetragonal crystal system with space group P4(1)2(1)2 and cell dimensions of a = b = 27.86 A and c = 52.72 A. The self-complementary DNA forms a six base pair right-handed double helix with two daunomycin molecules intercalated in the d(CpG) sequences at either end of the helix. Daunomycin in the complex has a conformation different from that of daunomycin alone. The daunomycin aglycon chromophore is oriented at right angles to the long dimension of the DNA base pairs, and the cyclohexene ring A rests in the minor groove of the double helix. Substituents on this ring have hydrogen-bonding interactions to the base pairs above and below the intercalation site. O9 hydroxyl group of the daunomycin forms two hydrogen bonds with N3 and N2 of an adjacent guanine base. Two bridging water molecules between the drug and DNA stabilize the complex in the minor groove. In the major groove, a hydrated sodium ion is coordinated to N7 of the terminal guanine and the O4 and O5 of daunomycin with a distorted octahedral geometry. The amino sugar lies in the minor groove without bonding to the DNA. The DNA double helix is distorted with an asymmetrical rearrangement of the backbone conformation surrounding the intercalator drug. The sugar puckers are C1,C2'-endo, G2,C1'-endo, C11,C1'-endo, and G12,C3'-exo. Only the C1 residue has a normal anti-glycosyl torsion angle (chi = -154 degrees), while the other three residues are all in the high anti range (average chi = -86 degrees). This structure allows us to identify three principal functional components of anthracycline antibiotics: the intercalator (rings B-D), the anchoring functions associated with ring A, and the amino sugar. The structure-function relationships of daunomycin binding to DNA as well as other related anticancer drugs are discussed.
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PMID:Interactions between an anthracycline antibiotic and DNA: molecular structure of daunomycin complexed to d(CpGpTpApCpG) at 1.2-A resolution. 356 61

The theory of structural parallelism put forward by A. A. Zavarzin (Senior) has been supported by the analysis of cytological specificity of effector organs involved in water-salt homeostasis, and of the excretory system of vertebrates and invertebrates. The similarity in morphofunctional organization of different excretory organs (i.e. the presence of ultrafiltration apparatus and cells which make it possible to absorb all vitally important substances) is likely to result from the fact that the excretory organ should excrete not only the final products of metabolism, but also any exogenic substances in addition to those which although important, are excessive for the organism. The brush border of asymmetrical epithelial cells of excretory organs is presumably a morphological expression of the structure which accounts for the inward transport of all physiologically important substances. Specificity of the membrane mechanism of water and sodium transport accounts for the identical principles in the structure of cells and areas of cell contacts of epithelia in different organs involved in the formation of hypotonic (saliva glands, renal tubules) or hypertonic fluids (salt glands, marine teleost gills).
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PMID:[The physiological determinants of the parallelism (unity) of histological structures]. 371 74

The interaction of the nonionic detergent Triton X-100 with phospholipid bilayers of liposomes made of egg yolk phosphatidylcholine was studied through the behavior of several physical properties. The dielectric permittivity spectra between 30 kHz and 13 MHz, the viscosity, the density, and the d.c. conductivity (1 kHz) of aqueous liposomes suspensions at various mole ratios were measured at 22 degrees C. For detergent-to-phospholipid ratios lower than 3, a dielectric relaxation process of characteristic frequency of about 50 kHz was recorded. This process does not appear for the liposomes in water, and becomes smaller and smaller for detergent-to-phospholipid ratios higher than 3. The viscosity of these suspensions showed a biphasic behavior, being remarkably increased by the detergent for concentration ratios lower than 3. The measured d.c. conductivity of these samples showed no relation with this process, being slightly increased when the detergent content is increased. As a conclusion of these results a well defined concentration range appears where the phospholipid organization changes forming highly asymmetrical structures.
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PMID:Effect of Triton X-100 on the physical properties of liposomes. 379 May 61

The two molecules of the asymmetric unit of the pH 3.5 conformer of alpha-chymotrypsin have been refined at 1.67-A resolution using restrained least squares methods with Hendrickson's program (PROLSQ). The final R factor is 0.179 (including 247 water molecules). The folding of the main chain of the independent molecules is the same within experimental error but the same does not generally apply to the side chain stereochemistry. From this we conclude that the folding of a protein structure is basically independent of most of the detailed stereochemistry of its side chains. The side chains of the interface region between the independent molecules display pronounced asymmetry. This asymmetry suggests that dynamic and asymmetrical structural changes take place at the time of oligomerization leading to more energetically favorable interactions for the dimer. Comparison of the structures of the independent molecules of alpha-chymotrypsin with the structure of monomeric gamma-chymotrypsin revealed that although the folding of the three molecules is essentially the same, numerous and significant differences pervade the side chain stereochemistry attributable to general flexibility. The specificity site of alpha-chymotrypsin is occupied by ordered water molecules in a similar way to gamma-chymotrypsin and other proteins. Some of these water molecules are displaced when substrate binds to the enzyme, while the others appear to help identify and position the aromatic side chain in catalysis.
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PMID:The refinement and the structure of the dimer of alpha-chymotrypsin at 1.67-A resolution. 398 Apr 76

42K+ tracer flux and steady-state conductance measurements were carried out with bilayer lipid membranes containing grisorixin, a carboxylic polyether antibiotic. When the membranes are placed between two bulk aqueous solutions of identical composition, the exchange or self-diffusion transmembrane flux of potassium is measured by a method which allows the characterization of the bilayer K+ permeability at the equilibrium state. The K+ self-diffusion flux increases with the pH in the range pH 6 to pH 9 and reaches a constant value for values above 9. This can be directly related to the increase of the surface concentration of the 1:1 complex formed by K+ and the deprotonated polyether at both bilayer membrane interfaces. The transport model initially proposed by Pressman and co-workers (Proc. Natl. Acad. Sci. USA 58:1949-1956, 1967) is again taken into consideration in the quantitative analysis of the flux data. The transmembrane transport of K+ results from the translocation of its neutral complex with grisorixin and the association-dissociation of the antibiotic with either potassium or protons taking place at both interfacial space layers while the turnover of the mobile carrier is accomplished under asymmetrical conditions by a translocation process of the acidic grisorixin. Using the data of some previous studies for mixed ionophore-lipid monolayers at the air/water interface and the present results for the self-diffusion flux measurements, it was possible to propose an evaluation of the more important parameters characterizing the transport; namely, the total surface concentration of grisorixin, the interfacial pK and the translocation rate constant of its potassium neutral complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transport of potassium ions across planar lipid membranes by the antibiotic, grisorixin: I. The equilibrium state and self-diffusion K+ fluxes. 409 53

This paper reports a theoretical analysis of osmotic transients and an experimental evaluation both of rapid time resolution of lumen to bath osmosis and of bidirectional steady-state osmosis in isolated rabbit cortical collecting tubules exposed to antidiuretic hormone (ADH). For the case of a membrane in series with unstirred layers, there may be considerable differences between initial and steady-state osmotic flows (i.e., the osmotic transient phenomenon), because the solute concentrations at the interfaces between membrane and unstirred layers may vary with time. A numerical solution of the equation of continuity provided a means for computing these time-dependent values, and, accordingly, the variation of osmotic flow with time for a given set of parameters including: P(f) (cm s(-1)), the osmotic water permeability coefficient, the bulk phase solute concentrations, the unstirred layer thickness on either side of the membrane, and the fractional areas available for volume flow in the unstirred layers. The analyses provide a quantitative frame of reference for evaluating osmotic transients observed in epithelia in series with asymmetrical unstirred layers and indicate that, for such epithelia, P(f) determinations from steady-state osmotic flows may result in gross underestimates of osmotic water permeability. In earlier studies, we suggested that the discrepancy between the ADH-dependent values of P(f) and P(DDw) (cm s(-1), diffusional water permeability coefficient) was the consequence of cellular constraints to diffusion. In the present experiments, no transients were detectable 20-30 s after initiating ADH-dependent lumen to bath osmosis; and steady-state ADH-dependent osmotic flows from bath to lumen and lumen to bath were linear and symmetrical. An evaluation of these data in terms of the analytical model indicates: First, cellular constraints to diffusion in cortical collecting tubules could be rationalized in terms of a 25-fold reduction in the area of the cell layer available for water transport, possibly due in part to transcellular shunting of osmotic flow; and second, such cellular constraints resulted in relatively small, approximately 15%, underestimates of P(f).
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PMID:Osmosis in cortical collecting tubules. A theoretical and experimental analysis of the osmotic transient phenomenon. 484 67

1. The relation between osmotic gradient and rate of osmotic water flow has been measured in rabbit gall-bladder by a gravimetric procedure and by a rapid method based on streaming potentials. Streaming potentials were directly proportional to gravimetrically measured water fluxes.2. As in many other tissues, water flow was found to vary with gradient in a markedly non-linear fashion. There was no consistent relation between the water permeability and either the direction or the rate of water flow.3. Water flow in response to a given gradient decreased at higher osmolarities. The resistance to water flow increased linearly with osmolarity over the range 186-825 m-osM.4. The resistance to water flow was the same when the gall-bladder separated any two bathing solutions with the same average osmolarity, regardless of the magnitude of the gradient. In other words, the rate of water flow is given by the expression (O(m) - O(s))/[R(o)' + (1/2)k' (O(m) + O(s))], where R(o)' and k' are constants and O(m) and O(s) are the bathing solution osmolarities.5. Of the theories advanced to explain non-linear osmosis in other tissues, flow-induced membrane deformations, unstirred layers, asymmetrical series-membrane effects, and non-osmotic effects of solutes could not explain the results. However, experimental measurements of water permeability as a function of osmolarity permitted quantitative reconstruction of the observed water flow-osmotic gradient curves. Hence non-linear osmosis in rabbit gall-bladder is due to a decrease in water permeability with increasing osmolarity.6. The results suggest that aqueous channels in the cell membrane behave as osmometers, shrinking in concentrated solutions of impermeant molecules and thereby increasing membrane resistance to water flow. A mathematical formulation of such a membrane structure is offered.
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PMID:Non-linear osmosis. 594 54

A patient developed lead neuropathy with an asymmetrical distal weakness of the four limbs and sensory signs. Tap water contained high amounts of lead and biopsy confirmed the intoxication. The electromyogram was altered from the onset of the disorder and was still abnormal one year after treatment with EDTA, which however brought frank improvement. Biopsies were taken from nerves of the upper and lower limbs. Examination of teased nerve fibers showed the predominance of fibers of small diameter and segmental demyelinization with signs of remyelination in the lower limbs. Semi-thin sections demonstrated depopulation of large myelinated fibers, regeneration clusters and Schwann cells with globular nuclei. Electron microscopy showed myelin sheath alterations and neuritic lesions, some hyperactive Schwann cells. Main alterations were seen in basal membranes of Schwann cells of unmyelinated fibers and endoneuronal capillaries. Such alterations to our knowledge have never been reported in human peripheral lead neuropathy, but have been described after experimental intoxication. These findings together with recent experimental studies allow a discussion about the site of entry of lead into the nerve and about its site of action on the various constituents of the peripheral nerve.
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PMID:[Peripheral nerves in a case of lead neuropathy]. 608 36

Maltoporin, a protein spanning Escherichia coli outer membranes, modifies electrical conductance of membranes due to its channel-forming properties. This observation was made by conductance measurements across planar bilayers which were derived from unextracted, isolated outer membrane vesicles using a porin-deficient E. coli strain. Alternatively, proteoliposomes reconstituted with detergent-solubilized homogeneous maltoporin and phospholipids were used. With either membrane preparation, channel conductance was observed, although no discrete conductance levels were detected. The presence of lipopolysaccharide, a bacterial glycolipid, was not required, nor did it affect channel activity. In the presence of the water-soluble periplasmic maltose-binding protein, conductance fluctuations occurred in discrete steps, demonstrating opening and closing events of channels. Multiple step sizes (1/3, 2/3 and 1 ns in 1 M KCl) in single channel traces suggest cooperative opening and closing of up to three channels. The action of maltose-binding protein is highly asymmetrical, and its affinity to maltoporin is very high (KD = 1.5 X 10(-7) M). Association of maltose-binding protein to maltoporin shifts, for a given polarity, the equilibrium between open and closed states in favour of closed states. This result matches earlier in vivo studies, and supports the physiological significance of the observations made.
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PMID:The periplasmic maltose-binding protein modifies the channel-forming characteristics of maltoporin. 631 10


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