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)

Recognition of metal cations by biological systems can be compared with the geochemical criteria for isomorphous replacement. Biological systems are more highly selective and much more rapid. Methods of maintaining an optimum concentration, including storage and transfer for the essential trace elements, copper and iron, used in some organisms are in part reproducible by coordination chemists while other features have not been reporduced in models. Poisoning can result from a foreign metal taking part in a reaction irreversibly so that the recognition site or molecule is not released. For major nutrients, sodium, potassium, magnesium and calcium, there are similarities to the trace metals in selective uptake but differences qualitatively and quantitatively in biological activity. Compounds selective for potassium replace all the solvation sphere with a symmetrical arrangement of oxygen atoms; those selective for sodium give an asymmetrical environment with retention of a solvent molecule. Experiments with naturally occurring antibiotics and synthetic model compounds have shown that flexibility is an important feature of selectivity and that for transfer or carrier properties there is an optimum (as opposed to a maximum) metal-ligand stability constant. Thallium is taken up instead of potassium and will activate some enzymes; it is suggested that the poisonous characteristics arise because the thallium ion may bind more strongly than potassium to part of a site and then fail to bind additional atoms as required for the biological activity. Criteria for the design of selective complexing agents are given with indications of those which might transfer more than one metal at once.
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PMID:Recognition of metal cations by biological systems. 0 15

Cardiac slowing during elevated intracranial pressure (ICP) could be due to direct activation of central nervous system (CNS) centers or it may be secondary to baroreceptor reflexes activated by the associated pressor response. In five pentobarbital-anesthetized dogs when ICP was raised to 50 mmHg the heart rate decreased 34.4 beats/min (+/-4.8 SE). This cardiac slowing occurred when ICP was elevated after sinoaortic denervation (-24 +/- 4.43 beats/min) and also during elevated ICP when changes in arterial pressure were prevented (-32.3 +/- 4.25 beats/min). These results indicate that the cardiac slowing is largely of CNS origin. In dogs given morphine with pentobarbital to achieve slower heart rates, raising ICP to 50 mmHg by left-sided intracranial balloon inflation led to cardiac dysrhythmias in 9 of 12 dogs. By contrast, raising ICP to 50 mmHg by right-sided intracranial balloon inflation only produced progressive sinus bradycardia. These responses were related to a combined enhancement of vagal and sympathetic activity. Differences observed between right- and left-sides balloon inflation may be partly related to asymmetrical engagement of the cardiac autonomic nerves. The results suggest that left-sided intracranial lesions are more likely to produce cardiac dysrhythmias.
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PMID:Heart rate and rhythm and intracranial pressure. 0 43

The simple architecture of the amphibian lung makes it possible to study the movement of substances across a barrier with permeability and bioelectric properties that are dominated by the alveolar epithelium. When mounted as a planar sheet between identical Ringer solutions the excised lung of the bullfrog exhibited a transmural electrical potential difference of nearly 20 mV (pleural surface positive) and a resistance of about 700 omega cm2. Unidirectional fluxes of 36Cl, Br-, I-, and SCN- across the short-circuited lung were asymmetrical. The net 36Cl- flow from pleura to lumen matched the short-circuit current after 1.5 h of voltage clamping, followed the kinetics of a saturable process, and was reduced by inhibitors of oxidative metabolism. These results suggest that halide and certain pseudohalide anions are secreted by the frog alveolar epithelium. Fluxes of Na+, K+, Ca+, HCO3-, TcO4-, SO42-, p-aminohippurate, gluconate, dinitrophenolate and water were compatible with passive diffusion of the probe molecules across the barrier. Measurements of lung oxygen consumption, ion fluxes and bioelectric properties have helped to pinpoint possible sites and modes of action of airborne agents, such as heavy metals, sulphates and nitrates, that may damage the mammalian pulmonary barrier.
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PMID:Ion transport across amphibian lung. 0 40

Transport properties of brush border microvilli and basal-lateral plasma membranes isolated from rat kidney cortex were studied by a millipore filtration technique. Brush border microvilli but not basal-lateral plasma membranes contain sodium dependent stereospecific transport system for D-glucose, L-phenylalanine and inorganic phosphate as indicated by saturability, countertransport and inhibition by structurally related compounds. Reduction of equilbrium uptake by increasing medium osmolarity suggests transport into an osmotically reactive space rather than binding to the membranes. Electrogenecity of the sodium-sugar and sodium-amino-acid cotransport system was established by their dependence on artificially imposed diffusion potentials. Also a NA+/H+ antiport system can be demonstrated in microvilli vesicles by demonstrating counterflow of both ions under short circuit conditions. Basal-lateral plasma membranes contain sodium independent stereospecific transport systems for sugars and amino acids. These results demonstrate a marked functional polarity of the cell membranes in respect to sodium dependent and sodium independent transport systems. This polarity in conjunction with the asymmetrical distribution of sodium between the intra- and extracellular space seems to enable the proximal tubule epithelial cells to perform active transepithelial transport.
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PMID:Polarity of proximal tubular epithelial cells in relation to transepithelial transport. 1 64

Tissues regulated by thyroid hormones contain chromatin-localized "receptors" that may be involved in the actions of these hormones. In this report, we describe some properties of these receptors after their solubilization from rat liver nuclei and their separation from nucleic acids and basic proteins. The nuclear extract and partially purified preparations contain a dominant class of binding sites which have a high affinity for triiodothyronine (3,5,3'-triiodo-L-thyronine, Kd approximately 1 nM) and for the biologically potent isopropyl diiodothyronine (3,5-diiodo-3'-isopropyl-L-thyronine, Kd congruent to 1 nM) and also bind thyroxine (3,5,3',5'-tetraiodo-L-thyronine, Kd approximately 5 nM) and reverse triiodothyronine (3,3',5'-triiodo-L-thyronine, Kd approximately nM). This binding activity elutes on Sephadex G-100 in an included peak which has a Stokes radius of 35 A and sediments on glycerol gradients at 3.5 S. From these data a molecular weight ratio of 50,500 and a frictional ratio of 1.4 were calculated, suggesting that the receptor is somewhat asymmetrical. There was a sharp decline in triiodothyronine binding by this component above pH 8.7 (optimum around pH 7.6) where there is marked dissociation of the 4' phenolic hydroxyl of triiodothyronine (pKalpha approximately 8.5). A similar decrease in thyroxine (pKalpha approximately 6.7) binding with pH increases in this range was not observed. Thus, ionization of the phenolic hydroxyl may influence binding. The solubilized preparations can also contain a minor specific-binding component that can be identified by binding analyses, and by G-100 or quaternary aminoethyl Sephadex chromatography. this component has a much lower affinity for triiodothyronine and isopropyl diiodothyronine than for thyroxine as compared to the major component. It probably has a pH optima around 6.0 and demonstrates and apparent tendency to aggregate. The minor component was not always identified by direct Scatchard analysis and may be generated in part from the major component as it was more commonly observed after storage or purification of the nuclear extract. Thus, at least two thyroid hormone-binding components can be present in extracts of purified rat liver nuclei; the minor component may be an altered form or subunit of the major component. The relative binding activities of triiodothyronine, isopropyl diiodothyronine, and thyroxine by the major component, similar to those in intact nuclei, parallel the biological potencies of these compounds, and suggest that the dominant binding is by biologically relevant receptors. Since ionization of the phenolic hydroxyl may influence binding, the lower activity of thyroxine relative to triiodothyronine may in part be due to the fact that at physiological pH, the phenolic hydroxyl of thyroxine is more dissociated than is that of triiodothyronine. The finding that this receptor is somewhat asymmetrical provides an indication of the shape of an intrinsic chromatin protein implicated in specific gene regulation...
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PMID:Solubilized nuclear "receptors" for thyroid hormones. Physical characteristics and binding properties, evidence for multiple forms. 1 62

1. Difference spectra of tryosyl residues obtained on denaturation of tropomycosin with urea or guanidinium chloride indicate that strong hydrophobic environments exist in the native coiled-coil state. 2. Solvent perturbation difference spectra indicate that tyrosyl residues are partially accessible to the solvent. The accessiblity decreases with increasing size of the solvent molecules. 3. Spectral pH titration of tyrosyl residues cannot provide information on the tyrosyl accessibility because conformational change accompanies the increase in pH. 4. Circular dichroism of tyrosyl and phenylalanyl residues is consistent with the effect of imposed conformational rigidity on the partially asymmetrical vibrational fine structure of the 1Lb absorption band of phenyl and benzyl chromophores; the effect is reduced by 70% on unfolding of tropomyosin.
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PMID:Circular dichroic and perturbation spectra of aromatic chromophores in rabbit tropomyosin. Topography of tyrosine residues. 1

Polynucleotide kinase (ATP:5'-dephosphopolynucleotide 5'-phosphotransferase, EC 2.7.1.78) has been purified approx. 1500-fold from calf thymus. This enzyme phosphorylates 5'-hydroxyl termini in DNA using ATP as phosphate donor. RNA is phosphorylated at a much lower rate than DNA. The reaction requires the presence of a divalent cation, preferably Mg2+ or Mn2+ and is sensitive to sulfhydryl antagonists. The optimum pH for enzyme activity is 5.5. Enzyme activity is inhibited by low concentrations of inorganic sulfate and by some sulfate polymers. The kinase-catalyzed incorporation of the terminal phosphate of ATP into polynucleotides is inhibited by other nucleoside and deoxynucleoside triphosphates. The enzyme molecule has a molecular weight of about 70 000 and a Stokes radius of 4.3 nm. It has a frictional ratio of 1.44 indicating an asymmetrical structure. Calf thymus tissue should provide a useful alternative source for preparation of mammalian polynucleotide kinase.
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PMID:Purification and properties of polynucleotide kinase of calf thymus. 2 43

1. A non-pepsin proteinase, proteinase 2, was successfully isolated free from pepsinogen (by repetitive chromatography on DEAE- and CM-celluloses) from the gastric mucosa of a patient with a duodenal ulcer and the uninvaded mucosa of a patient with a gastric adenocarcinoma. 2. Proteinases 1a and 1b, found in gastric adenocarcinoma, were not found in the gastic mucosa of these patients. 3. Proteinase 2 was shown to have an asymmetrical broad pH-activity curve with a maximum over the pH range 3.0-3.7. 4. Proteolytic activity of proteinase 2 was inhibited by pepstatin; the concentration of pepstatin giving 50% inhibition is of the order of 3nm. 5. Inhibition of proteolytic activity by carbenoxolone and related triterpenoids indicated that at pH 4.0 proteinase 2 possesses structural characteristics relating it to the pepsins and at pH 7.4 to the pepsinogens. 6. The sites of cleavage of the B-chain of oxidized insulin for proteinase 2 at pH 1.7 and pH 3.5 were shown to be similar to those previously established for human pepsin 3 and for the cathepsin E of rabbit bone marrow. 7. The non-pepsin proteinase 2 (cathepsin) of human gastric mucosa has properties more similar to cathepsin E than to the cathepsins D.
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PMID:The isolation and properties of a non-pepsin proteinase from human gastric mucosa. 2 49

Calcium ions can trigger an emission of light from Veretillum cynomorium lumisomes (bioluminescent vesicles) under conditions where they are not lysed. This process does not require a metabolically-linked source of energy, but is dependent upon the nature of the ions present inside and outside the vesicles. The Ca2+-triggered bioluminescence is stimulated by an asymmetrical distribution of cations or anions. Either high internal sodium or high external chloride is required for the maximal effect. When sodium is present outside the structure and potassium inside, the slow inward diffusion of calcium is decreased. Unbalanced diffusion of internal cations also stimulates the bioluminescence, suggesting control of the calcium influx by an electrochemical gradient. It is assumed that rapid outward diffusion of sodium or inward diffusion of chloride generates an electrical potential difference (inside negative) which drives the Ca2+-influx. With purified lumisomes it has been shown that Ca2+-triggered bioluminescence and calcium uptake (presumably net uptake) were correlated. In two instances uptake of the lipophilic cation dibenzyldimethylammonium has given direct evidence for the existence of a potential difference. With NaCl-loaded vesicles, it has not been possible to demonstrate an uptake of lipophilic cations but experiments with 22Na and 42D indicated a higher rate of sodium efflux, in accord with the proposed hypothesis.
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PMID:Control of the Ca2+-triggered bioluminescence of Veretillum cynomorium lumisomes. 3 Apr 80

Considerable evidence has accumulated indicating that one neurotransmitter in the excitatory cortico-striatal tract is glutamate. Lesions of the tract result in reductions in the striatum of glutamate levels as well as high affinity uptake of glutamate into synaptosomes. Furthermore, such lesions eliminate the neurotoxicity of the glutamate analog kainic acid when injected into the striatum. The fine structure of the cortico-striatal pathway was studied to provide evidence regarding the morphology of glutamate nerve endings. Seven days after injection of 3H-proline (20-25 mu Ci) into the rat frontal cortex, axonally transported label appeared in the striatum with uniform distribution in a single type of nerve ending. The labeled boutons had common round vesicles and made asymmetrical contacts, mostly with dendritic spines. This morphology is typical of excitatory synapses, and similar to that previously shown for cholinergic boutons in the striatum. In four animals similarly injected with 3H-proline, kainic acid was administered directly into the striatum to induce degeneration of postsynaptic elements eight to ten hours before sacrifice. In areas affected by these injections, grains appear in patches, possibly resulting from glial swelling. Labeled boutons were seen almost four times as often in synaptic contact with degenerating dendritic elements as with normal ones. The data provide morphological evidence as to the nature of the probable glutamatergic boutons in the striatum, and show the close relationship of such boutons with the neurotoxic effects of kainic acid. This would be anticipated in view of the dependency of kainic acid neurotoxicity on the integrity of the cortico-striatal pathway.
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PMID:Fine structural analysis of the cortico-striatal pathway. 3 35


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