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)

The synthesis and characterization of an N-methyl-N-nitrosourea (MNU) analogue that is covalently linked to a methidium nucleus is described. At 37 degrees C in pH 8.0 buffer 9 hydrolyzes via pseudo-first-order kinetics, with a calculated t1/2 = 77 min. By use of polyacrylamide sequencing gels the formation of piperidine-labile N7-methylguanine adducts from the reaction of 9 and MNU with 5'-32P-end-labeled DNA restriction fragments is reported. DNA methylation by 9 in 10 mM Tris buffer is enhanced with increasing ionic strength (50-200 mM NaCl), which contrasts to the inhibition of MNU-induced cleavage with increasing salt. In addition, 9 methylates all G sites equally, while MNU shows a clear preference for d(G)n (n greater than or equal to 3) runs and an asymmetrical methylation pattern within these G-rich regions. The results are discussed in terms of the delivery of the MNU moiety to the DNA target by a non-sequence-specific intercalation process and the subsequent hydrolytic generation of a nondiffusible alkylating intermediate.
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PMID:Synthesis of an N-methyl-N-nitrosourea linked to a methidium chloride analogue and its reactions with 32P-end-labeled DNA. 321 65

Nuclear thyroid hormone receptors of patients with the syndrome of resistance to thyroid hormone were investigated in cell lines from seven patients in four affected families and compared to results from six normals. Fibroblasts cultured from skin biopsies were used. When binding affinity and capacity for L-triiodothyronine (T3) were examined by incubating whole cells or isolated nuclei, no significant differences were found. The amount of receptor released during the incubation of nuclei (9.3% to 19.0% of total nuclear receptors) was also within the normal range in these patients. When T3 binding assays were performed on 0.3 mol/L KCl extracted receptor, a significant decrease in binding capacity (MBC) without a difference in binding affinity (Ka) was observed in four patients and a lower Ka with normal MBC was found in two patients. Recovery of receptors in saline extracts, from patients' fibroblasts showing a low MBC, was low in comparison to normals. Lability of salt extracted receptors at 38 degrees C was normal and salt extractability of T3 occupied receptors, examined by incubation of [125I]-T3 labeled nuclei with various concentrations of KCl, was only slightly decreased. This lower salt extractability of receptors was insufficient to account for the low MBC obtained by Scatchard analysis of T3 binding to nuclear extracts. Gel filtration and density gradient sedimentation of salt-extracted receptors showed Stokes radius of 34 A, and sedimentation coefficient of 3.4 S in all patients and normals. From these values, molecular weight of 49,000 and total frictional ratio (f/fo) of 1.4 were calculated for nuclear receptors from patients and normals, suggesting a somewhat asymmetrical shape of receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of nuclear thyroid hormone receptors of cultured skin fibroblasts from patients with resistance to thyroid hormone. 356 Dec 54

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

1. Mechanisms of ion transport across the choroidal epithelium were investigated using an in vitro preparation of the frog choroid plexus.2. Sodium was actively transported across the plexus from the vascular to the ventricular surface by an ouabain sensitive electrically silent pump. As in other epithelial membranes the rate of sodium transport was stimulated by the presence of bicarbonate ions in the Ringer solutions. Chloride and bicarbonate ions accompany the net flux of sodium across this tissue.3. Some experiments suggest that potassium is actively transported from the ventricular to the serosal surface, and that the rate of transport is a function of the extracellular potassium concentration.4. No evidence was obtained to suggest that calcium is actively transported across this tissue in either direction.5. Diamox, ethoxyzolamide, pitocin, pitressin, hydrocortisone, amiloride, spironolactone and anoxia all failed to influence sodium transport.6. The sequence of passive ion permeation across the plexus was P(Rb) approximately P(K) > P(Cs) approximately P(Na) approximately P(Cl) approximately P(HCO3) > P(Li) as deduced from diffusion potential measurements. At least for Na, K and Cl there was a good correlation between the permeability coefficients derived from unidirectional flux measurements and from electrical parameters. This indicates that exchange diffusion is unimportant as a mechanism for passive ion transport.7. The instantaneous current-voltage curves were linear in both symmetrical and asymmetrical salt solutions and the choroid plexus conductance was found to be directly proportional to the external salt concentration. These and other lines of evidence suggest that the major route of passive ion permeation across this epithelium is via the tight junction route and not through the cell interior.8. These results are discussed in relation to the in vivo studies of c.s.f. secretion and the mechanisms of active and passive ion transport across other epithelial membranes such as the gall-bladder, intestine and renal proximal tubule.
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PMID:Mechanisms of ion transport across the choroid plexus. 453 45

This paper describes dissipative Cl(-) transport in "porous" lipid bilayer membranes, i.e., cholesterol-containing membranes exposed to 1-3 x 10(-7) M amphotericin B. P(DCl) (cm.s(-1)), the diffusional permeability coefficient for Cl(-), estimated from unidirectional (36)Cl(-) fluxes at zero volume flow, varied linearly with the membrane conductance (Gm, ohm(-1).cm(-2)) when the contributions of unstirred layers to the resistance to tracer diffusion were relatively small with respect to the membranes; in 0.05 M NaCl, P(DCl) was 1.36 x 10(-4) cm.s(-1) when Gm was 0.02 ohm(-1).cm(-2). Net chloride fluxes were measured either in the presence of imposed concentration gradients or electrical potential differences. Under both sets of conditions: the values of P(DCl) computed from zero volume flow experiments described net chloride fluxes; the net chloride fluxes accounted for approximately 90-95% of the membrane current density; and, the chloride flux ratio conformed to the Ussing independence relationship. Thus, it is likely that Cl(-) traversed aqueous pores in these anion-permselective membranes via a simple diffusion process. The zero current membrane potentials measured when the aqueous phases contained asymmetrical NaCl solutions could be expressed in terms of the Goldman-Hodgkin-Katz constant field equation, assuming that the P(DNa)/P(DCl) ratio was 0.05. In symmetrical salt solutions, the current-voltage properties of these membranes were linear; in asymmetrical NaCl solutions, the membranes exhibited electrical rectification consistent with constant-field theory. It seems likely that the space charge density in these porous membranes is sufficiently low that the potential gradient within the membranes is approximately linear; and, that the pores are not electrically neutral, presumably because the Debye length within the membrane phase approximates the membrane thickness.
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PMID:Chloride transport in porous lipid bilayer membranes. 470 8

A model is developed for hemoglobin which depends on six Bohr groups per tetramer of hemoglobin. These six groups are assumed to be located in six regions between the four subunits of hemoglobin. When the Bohr groups are assumed to be perturbed in an asymmetrical manner on binding oxygen, these groups then generate the cooperative interactions of hemoglobin. This approach makes it possible to explain oxygen binding, the Bohr effect, specific salt effects, and aggregation effects in a unified manner.
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PMID:Model for the action of hemoglobin. 527 67

The electrophysiological properties of the dorsal and ventral canine lingual epithelium are studied in vitro. The dorsal epithelium contains a special ion transport system activated by mucosal solutions hyperosmotic in NaCl or LiCl. Hyperosmotic KCl is significantly less effective as an activator of this system. The lingual frenulum does not contain the transport system. In the dorsal surface it is characterized by a rapid increase in inward current and can be quantitated as a second component in the time course of either the open-circuit potential or short-circuit current when the mucosal solution is hyperosmotic in NaCl or LiCl. The increased inward current (hyperosmotic response) can be eliminated by amiloride (10(-4) M). The specific location of this transport system in the dorsal surface and the fact that it operates over the concentration range characteristic of mammalian salt taste suggests a possible link to gustatory transduction. This possibility is tested by recording neural responses in the rat to NaCl and KCl over a concentration range including the hyperosmotic. We demonstrate that amiloride specifically blocks the response to NaCl over the hyperosmotic range while affecting the KCl response significantly less. The results suggest that gustatory transduction for NaCl is mediated by Na entry into the taste cells via the same amiloride-sensitive pathway responsible for the hyperosmotic response in vitro. Further studies of the in vitro system give evidence for paracellular as well as transcellular current paths. The transmural current-voltage relations are linear under both symmetrical and asymmetrical conditions. After ouabain treatment under symmetrical conditions, the short-circuit current decays to zero. The increase in resistance, though significant, is small, which suggests a sizeable shunt pathway for current. Flux measurements show that sodium is absorbed under symmetrical conditions. Mucosal solutions hyperosmotic in various sugars also induce an amiloride-sensitive inward current. In summary, this work provides evidence that the sodium taste receptor is most probably a sodium transport system, specifically adapted to the dorsal surface of the tongue. The transport paradigm of gustation also suggests a simple model for electric taste and possible mechanisms for sweet taste.
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PMID:The active ion transport properties of canine lingual epithelia in vitro. Implications for gustatory transduction. 633 Feb 75

Bilirubin is a linear tetrapyrrole whose conformation is affected by internal hydrogen bonds formed between the carboxyl side chains and dipyrromethenone rings. Structural variations include: constitutional isomerism of the vinyl or carboxyethyl side chains, geometric isomerism of the methene bridges, tautomerism of the lactam groups, conformational rotations about the central methylene bridge and ionization of one or both carboxyl groups. Aggregation of the dianion into dimers and multimers may occur. The pKa' values of the two carboxyl groups are affected greatly by the environment and may differ widely in micellar solutions like bile. Solubility of bilirubin in water is less than 1 nM at pH = 7 and about 0.1 microM at pH = 8. Nonetheless, it dissolves poorly in most lipid solvents, except for asymmetrical chloroalkanes. Hydrogen bond-breaking solvents, especially dimethyl sulfoxide, are most effective in solubilizing bilirubin. In bile salt solutions, solubility of bilirubin is well above the concentrations of unconjugated bilirubin found in normal human gallbladder bile, and is impaired by lecithin but unaffected by cholesterol. At physiological pH in bile salt solutions, bilirubin is predominantly in its monoanion form that binds readily to the micelles. In such solutions, addition of physiological concentrations of calcium precipitates calcium bilirubinate, leaving residual bilirubin concentrations of up to 15 microM in 50 mM taurocholate or close to the maximum bilirubin concentrations in normal bile. Studies in which disodium bilirubinate is dissolved in bile salt solutions and pH is adjusted to the physiological range reveal that metastable supersaturation with bilirubin may occur and that a mesophase may also form in the presence of lecithin, akin to that seen with cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bilirubin chemistry, ionization and solubilization by bile salts. 647 84

Dinucleosomes purified from micrococcal nuclease digests of steer kidney nuclei were stripped of H1 histone by exposure to 0.50 M NaCl. They were then formed in a complex with individual subfractions of calf thymus H1 histone by dialysis of histone-dinucleosome mixtures from 0.50 M NaCl to concentrations of NaCl between 0 M and 0.08 M; between 0.30 M and 0.10 M the complexes precipitated, and so were not included in the study. The presence of H1 in the complexes was shown to cause an asymmetrical, ordered condensation as revealed by distortions of the circular dichroic spectrum of the DNA. The distortions were negligible at 0.04 M NaCl and below, and increased as a function of ionic strength between 0.05 M and 0.08 M. The degree of distortion of the spectrum, and therefore the nature of dinucleosome condensation, differed greatly from one H1 subfraction to the next. One of the three subfractions tested had almost no effect on the circular dichroism in comparing its dinucleosome complex to H1-depleted dinucleosomes. The other subfractions to different degrees produced large distortions that resulted in spectra that were of the psi type at the higher salt concentration.
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PMID:Condensation of dinucleosomes by individual subfractions of H1 histone. 727 70

Melittin, the main basic and hydrophobic peptide of bee venom, displays marked detergent-like properties. At high peptide concentration, and depending on salt and pH, it forms a tetramer. This is prevented by using urea. A purification procedure in presence of 4.0 M urea was developed to prepare melittin in its monomeric form, free of other venom constituents such as N alpha-formyl melittin, degradation products of peptides and phospholipase A2. NH2-residues on the melittin molecule were modified by reaction with acetic anhydride to alter the asymmetrical charge distribution supposed to confer detergent-like properties to the molecule. This gave rise to di- and mono acetyl derivatives which could be used, once isolated, to study further the melittin structure-activity relationship.
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PMID:Purification and chemical characterization of melittin and acetylated derivatives. 743 62


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