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

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

Transient responses of minute ventilation (VE), oxygen consumption (VO2), carbon dioxide output (VCO2), cardiac output (Q) and heart rate (HR) to step, impulse, sinusoidal and ramp changes in exercise load were studied in healthy human subjects at the moderate load range. Exercise was performed in the upright position using a bicycle ergometer. The transient responses to step and impulse forcings fitted essentially to a second-order model consisting of a fast and a slow component, while the responses to sinusoidal and ramp forcings fitted to a first-order model. No significant asymmetry was observed between the on- and off-responses to step forcing. On the contrary, the mean response time (MRT = pure time delay + time constant) of variables to ascending ramp forcing was prolonged, while the MRT to descending ramp was shortened with decreasing ramp slope. The on- and off asymmetry of the MRT was observed in VE, VO2 and VCO2 and, to a lesser extent, also in HR and Q. A non-linear blood flow model, which simulates changes in the wash-in and wash-out time of metabolic substances into and from the chemoreceptor, has been proposed as a likely explanation for the asymmetrical responses. It was concluded that the regulatory system of respiration and circulation might be essentially non-linear in its operation, despite the fact that the cardiorespiratory responses during exercise seemed to fit linear models.
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PMID:Kinetics of respiratory and circulatory responses to step, impulse, sinusoidal and ramp forcings of exercise load in humans. 159 81

We have proposed a three step model for the specification of left-right in mammalian embryos. The fundamental assumption is that handedness is imparted by an asymmetrical molecule. Conversion of molecular asymmetry to the cellular level gives a property to one side of the embryo to bias an otherwise random generation of an asymmetrical gradient which can be interpreted by developing organs. Rat embryos, treated at discrete stages, show a window of sensitivity for disruption of handedness, which may reflect the time of conversion/biasing. Heat shock and several chemicals cause left-right inversion in up to 50% of embryos exposed during neural groove formation. Earlier stages are less sensitive; no treatment begun after foregut pocket formation influences asymmetry. Evidence for cellular interactions in left-right specification comes from the apparent rescue of iv/iv mutant embryos in chimeras. We are looking for molecular left-right disparity before morphological asymmetry but detect no differences in two-dimensional protein profiles. Using an indirect measure, we find a right-left gradient of tissue oxygen in embryos at the 20-30 somite stage. This may reflect asymmetrical vasculature, as we have suggested to explain drug-induced asymmetrical limb malformations.
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PMID:Development of handed body asymmetry in mammals. 166 58

Many human infants are born inappropriately small as a result of stress suffered during intrauterine life. Acute reductions in oxygen delivery to fetal tissues have therefore been studied in animals so that insight can be obtained into the adaptive mechanisms that underlie human developmental abnormalities. It is now known that during moderate hypoxic stress fetal arterial blood pressure is variably increased while heart rate and cardiac output are depressed; blood volume is reduced but cardiac output is redistributed to spare the myocardium, brain and adrenal glands at the expense of most other organs. Also a greater fraction of oxygen-rich venous blood from the placenta is returned to the heart for distribution. Spared organs are those that grow disproportionately well in human asymmetrical intrauterine growth retardation (IUGR). These cardiovascular responses are not fully understood although elevated fetal plasma levels of catecholamines and a host of fetal hormones are undoubtedly important. Chemical sympathectomy does not abolish the blood flow redistribution phenomenon, which implies that autoregulatory effects may be responsible for some of the redistribution of blood flow. Fetal hypoxaemia and metabolic abnormalities are sequelae often found with human IUGR, suggesting placental exchange defects. IUGR placentas appear to have defective transport mechanisms for many nutrients. Animal studies suggest that the placenta will give priority to its own needs over those of the fetus, when necessary, to support its own growth and function.
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PMID:Fetal response to intrauterine stress. 185 10

Interleukin 1 beta (IL-1 beta) is a polypeptide with pro-inflammatory and immunopotentiating effects in vivo and in vitro. With relevance to rheumatoid arthritis (RA) IL-1 augments release of prostanoids, proteinases and oxygen metabolites and is a potent inducer of bone and cartilage resorption. Although high levels of IL-1 have been found in rheumatoid synovial fluids, intra-individual variation in IL-1 production has made it difficult to correlate these levels with disease activity. To overcome this problem we have studied patients with symmetrical and asymmetrical knee joint inflammation. Local disease activity was documented using Ritchie score and joint circumference; IL-1 beta levels were quantitated in synovial fluid by ELISA. In patients with symmetrical joint involvement almost identical levels of IL-1 beta were detected in the right and left knee joints. In contrast, in patients exhibiting asymmetrical knee joint involvement, IL-1 beta levels in the inflamed joints were significantly higher than in the contralateral joints. The study provides further evidence for the role of IL-1 in the pathogenesis of rheumatoid inflammation.
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PMID:Interleukin 1 beta in synovial fluid is related to local disease activity in rheumatoid arthritis. 207 74

Six new methylenephosphonate analogues of P1P4-bis-(5',5'''-adenosyl) tetraphosphate, Ap4A, having P2-P3 carbon bridges CF2, CCl2 and CH2CH2 or P1-P2 and P3-P4 carbon bridges CF2, CCl2 and CH2CH2 in the tetraphosphate chain, were examined as substrates or inhibitors for two specific Ap4A-degrading enzymes: (asymmetrical) Ap4A hydrolase (EC 3.6.1.17) from yellow-lupin seeds and (symmetrical) Ap4A hydrolase (EC 3.6.1.41) from Escherichia coli. All analogues in which the central oxygen atom was replaced by a stable carbon bridge were hydrolysed by the asymmetrical hydrolase (CF2 greater than CCl2 greater than O greater than CHBr greater than CH2 greater than CH2CH2). As expected, these analogues were not hydrolysed by the symmetrical hydrolase, which was also unable to act on analogues having P1-P2 and P3-P4 carbon bridges.
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PMID:Studies on some specific Ap4A-degrading enzymes with the use of various methylene analogues of P1P4-bis-(5',5'''-adenosyl) tetraphosphate. 255 85

We show that the technique of exciting a differential pressure transducer at one port to measure its differential gain yields incorrect results in the case of asymmetrical differential pressure transducers but is acceptable in the case of symmetrical transducers. We have measured the common-mode gain of a symmetrical and an asymmetrical differential pressure transducer from 1 Hz to 100 Hz, both directly and by computation from differential gain measurements. No compensation for common-mode error is necessary when a symmetrical transducer is used in mechanically ventilated neonates. We have also measured the frequency response of neonatal Fleisch and screen pneumotachographs connected to Validyne MP45 differential pressure transducers in air, 60% oxygen and 100% oxygen, and concluded that the effect of oxygen concentration is small below 40 Hz. However, the normalised frequency response of the flow transducer differs markedly from unity at frequencies inside the flow bandwidth generated by neonatal pressure cycled ventilators and dynamic correction is therefore necessary.
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PMID:Measurement of the frequency response and common-mode gain of neonatal respiratory pressure and flow measurement systems. Part 2: Results. 262 65

Novel analogues of P1,P4-bis(5'-adenosyl) tetraphosphate, Ap4A (1), have been prepared with sulphur substituents at P1 and P4 and either oxygen or methylene bridges at the P2,P3-position. Separation of three isomers of the ApspCH2ppsA species has been achieved by a combination of mplc and hplc and the Rp,Rp, Rp,Sp, and Sp,Sp diastereoisomers identified on the basis of selective enzymatic hydrolysis using snake venom phosphodiesterase. Each of these three isomers is a strong competitive inhibitor of the specific Ap4Aase from Artemia and is highly resistant to the asymmetric cleavage normally catalysed by this enzyme.
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PMID:Synthesis and resistance to enzymic hydrolysis of stereochemically-defined phosphonate and thiophosphate analogues of P1,P4-bis(5'-adenosyl) tetraphosphate. 282 89

Differential oxygen binding measurements obtained over the pH range 6.95 to 9.10 at 25 degrees C have allowed a detailed description of the alkaline Bohr effect of human hemoglobin Ao. Phenomenological analysis of the data in terms of the Adair equation shows that: (1) the oxygen binding curves are asymmetrical with the population of the triply oxygenated species being negligible throughout the pH range studied: (2) the shape of the oxygen binding curve is affected by pH, especially at low saturation; and (3) the maximum O2-proton linkage is -0.52 mole of proton per mole of oxygen at pH 7.4. A possible molecular mechanism of the Bohr effect is proposed within the framework of an allosteric model which accounts for the low population of triply oxygenated hemoglobin species. At least three Bohr groups are necessary for a quantitative description of the alkaline Bohr effect. Two of these groups titrate in the range of the His146 beta and Vall alpha residues, which have long been identified as the main alkaline Bohr groups, and altogether contribute 84% of the alkaline Bohr effect at physiological pH. A third ionizable group, linked to oxygenation presumably at the beta chains, is implicated and is titrated in a pH range characteristic of a surface histidyl residue.
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PMID:Alkaline Bohr effect of human hemoglobin Ao. 284 May 10


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