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Query: UMLS:C0027960 (mole)
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1. Giant axons from the squids Dosidicus gigas, Loligo forbesi and Loligo vulgaris were internally perfused with 550 or 275 mM KF plus sucrose and bathed in artificial sea water containing 45Ca, 28Mg or mixtures of 45Ca-28Mg or 45Ca-22Na. Resting influxes and extra influxes during voltage-clamp pulses were measured by collecting and counting the internal perfusate. 2. For Dosidicus axons in 10 mM-CaCl2 the resting influx of calcium was 0-016 +/- 0-007 p-mole/cm2 sec and a linear function of external concentration. For two experiments in 10 and 84-7 mM-CaCl2, 100 nM tetrodotoxin had no effect. Resting calcium influx in 10 mM-CaCl2 was 0-017 +/- 0-013 p-mole/cm2 sec for Loligo axons. 3. With 55 mM-MgCl2 outside the average resting magnesium influx was 0-124 +/- 0-080 p-mole/cm2 sec for Loligo axons. Discarding one aberrant point the value is 0-105 +/- 0-046 which is not significantly different from the resting calcium influx for Dosidicus fibres in 55 mM-CaCl2, given as 0-094 p-mole/cm2 sec by the regression line shown in Fig. 1. In two experiments 150 nM tetrodotoxin had no effect. 4. With 430 mM-NaCl outside 100 nM tetrodotoxin reduced the average resting influx of sodium in Dosidicus axon from 27-7 +/- 4-5 to 25-1 +/- 6-2 p-mole/cm2 sec and for Loligo fibres in 460 mM-NaCl from 50-5 +/- 4 to 20 +/- 8 p-mole/cm2 sec. 5. Using depolarizing pulses of various durations, the extra calcium influx occurred in two phases. The early phase was eliminated by external application of tetrodotoxin. The results of analysis are consistent with, but do not rigorously demonstrate, the conclusion that the tetrodotoxin sensitive calcium entry is flowing through the normal sodium channels (cf. Baker, Hodgkin & Ridgway, 1971). 6. Measurements of extra influxes using 22Na and 45Ca simultaneously indicate that the time courses of tetrodotoxin sensitive calcium and sodium entry are similar but not necessarily identical. It is very doubtful that any significant calcium entry occurs before the sodium or is involved in the activation of the sodium system. 7. These measurements confirm for Loligo, as previously shown for Dosidicus axons, that the magnitude and time course of the sodium entry during a depolarizing pulse deduced from electrical measurements is the same as that measured with 22Na. 8. Using 28Mg, or mixtures of 45Ca and 28Mg, we observed a single phase of magnesium entry which was insensitive to external tetrodotoxin or internal tetraethyl ammonium. The magnitude of the magnesium influx was considerably greater than the calcium extra entry and large enough to have been detected in the experiments of Meves & Vogel (1973) if it represented current. 9. We suggest the possibility that the calcium and magnesium extra influxes, after external treatment with tetrodotoxin, during a depolarizing pulse, do not contribute to the measured current.
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PMID:Simultaneous measurements of magnesium, calcium and sodium influxes in perfused squid giant axons under membrane potential control. 120 93

We have stabilized the d(A)10.2d(T)10 and d(C+LT4C+3).d(G3A4G3).d(C3T4C3) triple helices with either NaCl or MgCl2 at pH 5.5. UV mixing curves demonstrate a 1:2 stoichiometry of purine to pyrimidine strands under the appropriate conditions of pH and ionic strength. Circular dichroic titrations suggest a possible sequence-independent spectral signature for triplex formation. Thermal denaturation profiles indicate the initial loss of the third strand followed by dissociation of the underlying duplex with increasing temperature. Depending on the base sequence and ionic conditions, the binding affinity of the third strand for the duplex at 25 degrees C is two to five orders of magnitude lower than that of the two strands forming the duplex. Thermodynamic parameters for triplex formation were determined for both sequences in the presence of 50 mM MgCl2 and/or 2.0 M NaCl. Hoogsteen base pairs are 0.22-0.64 kcal/mole less stable than Watson-Crick base pairs, depending on ionic conditions and base composition. C+.G and T.A Hoogsteen base pairs appear to have similar stability in the presence of Mg2+ ions at low pH.
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PMID:Thermodynamics of triple helix formation: spectrophotometric studies on the d(A)10.2d(T)10 and d(C+3T4C+3).d(G3A4G3).d(C3T4C3) triple helices. 221 68

The LD50 for fluoride was elevated from less than 60 mg F/kg body weight to 172 mg F/kg when magnesium (as MgCl2), equivalent to 3 times that of F, was administered by gavage 30 min after the F dose. A dose of 30 mg F/kg elevated the mean steady state of F in serum nearly 1.5-fold and in femoral bone nearly 2-fold when administered with or without the subsequent Mg dose and observed 24 h after the electrolyte dosages. Also, in 24-hour urine the mean F excretion was highest in the F and FMg groups. The total F excretion (fecal + urinary) was elevated 8- and 10-fold when fluoride was administered with or without magnesium, as compared to control levels. Magnesium administration with fluoride did not significantly modify the above mean values of the group given fluoride alone. This suggests that interference with the absorption of fluoride was not the primary protective function of magnesium against the acute toxicity of fluoride. Additional experiments, conducted to further clarify the toxic mechanism of fluoride and the protective mechanism of magnesium, resulted in the following findings: An intraperitoneal dose of 20 mg F/kg elevated fluoride concentration in serum in 1 h about 20 times compared to the controls. Magnesium injected simultaneously with fluoride did not modify the effect of fluoride alone. No significant changes were found in the concentrations of K, Mg, Na or Ca of the lung, skeletal muscle, kidney or liver after these injections except for some trend of elevation of Ca in the heart. However, after a dose of 30 mg F/kg i.p., the heart Ca/Mg mole ratio was elevated within 1 h from 0.037 to 0.194, while all of these rats died within 1 h after the injections. When magnesium, equivalent to 3 times the amount of fluoride was injected, this mole ratio was only 0.095, and all rats in this group survived over 1 h. These results suggest that the lethality of fluoride may be dominantly mediated by the elevated Ca (Ca/Mg ratio) in the heart muscle and that this is correctable by Mg.
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PMID:The LD50, excretion and serum and bone levels of F after a high single F and F + Mg dose in rats with findings on cardiac Ca and Mg. 233 14

1. Membrane currents and membrane potentials of the fresh-water ciliate Stylonychia mytilus were investigated by voltage-clamp and constant-current injection techniques. 2. The Ca-dependent action potential of Stylonychia in a solution containing 0.1 mM-CaCl2 was prolonged by the addition of Mg or Na ions. 3. In a nominally Ca-free solution, containing 2 mM-MgCl2, the cells generated repetitive, spontaneous action potentials of relatively small amplitude (17 mV). The addition of 0.5 microgram concanavalin A/ml completely inhibited these action potentials in 2 mM-Mg. 4. In voltage-clamp experiments in standard solution, the inward current-voltage relationship has two maxima, confirming the existence of two different voltage-dependent Ca currents in Stylonychia: inward current I and II. In a nominally Ca-free, Mg-containing solution, the remaining inward current was inhibited by concanavalin A, a specific inhibitor of inward current I. No residual second inward current (current II) was detected in a solution containing Mg and concanavalin A. 5. Experiments, with altered ratio of Ca and Mg ions and constant concentration of divalent cations (mole-fraction experiments), showed that Mg and Ca do not inhibit each other's passage through channel I. Calculations assuming a Ca-channel model with one cation-binding site per ion channel I showed good correlation with the experimental data. 6. A similar inward current was seen after replacement of Mg by Na in nominally Ca-free solution.
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PMID:Different properties of two voltage-dependent inward currents of the ciliate Stylonychia mytilus. 244 46

Reactivity of tubulin SH groups, estimated by the slope to the curve in the SH-SS exchange reaction with 5-5' dithiobis (2-nitrobenzoic acid), was compared with that of bovine serum albumin (BSA) and studied in presence of various ligands. A small part of tubulin SH groups (12%) showed a higher reactivity, while the remaining portion had a smaller reactivity than that of BSA. The SH group reactivity of tubulin but not the total amount (12.8 mu/mole) diminished when assayed with colchicine and MgCl2 (0.1 and 0.2 mM, respectively); 0.2 mM CaCl2 increased the reactivity at the maximum level. On the basis of the biological role of tubulin SH groups and of the opposite effects exerted by Ca++ and Mg++ on the protein, the results presented here seem to indicate a correlation between conformational states of tubulin and its biological functions.
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PMID:The SH-SS exchange reaction between the Ellman's reagent and protein containing SH groups as a method for determining conformational states: tubulin. 274 39

2-Azidoadenosine 5'-diphosphate (2-azido-ADP) labeled with 32P in the alpha-position was prepared and used to photolabel the nucleotide binding sites of beef heart mitochondrial F1-ATPase. The native F1 prepared by the procedure of Knowles and Penefsky [Knowles, A. F., & Penefsky, H. S. (1972) J. Biol. Chem. 247, 6617-6623] contained an average of 2.9 mol of tightly bound ADP plus ATP per mole of enzyme. Short-term incubation of F1 with micromolar concentrations of [alpha-32P]-2-azido-ADP in the dark in a Mg2+-supplemented medium resulted in the rapid supplementary binding of 3 mol of label/mol of F1, consistent with the presence of six nucleotide binding sites per F1. The Kd relative to the reversible binding of [alpha-32P]-2-azido-ADP to mitochondrial F1 in the dark was 5 microM in the presence of MgCl2 and 30 microM in the presence of ethylenediaminetetraacetic acid. A linear relationship between the percentage of inactivation of F1 and the extent of covalent photolabeling by [alpha-32P]-2-azido-ADP was observed for percentages of inactivation up to 90%, extrapolating to 2 mol of covalently bound [alpha-32P]-2-azido-ADP/mol of F1. Under these conditions, only the beta subunit was photolabeled. Covalent binding of one photolabel per beta subunit was ascertained by electrophoretic separation of labeled and unlabeled beta subunits based on charge differences and by mapping studies showing one major radioactive peptide segment per photolabeled beta subunit.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Photoaffinity labeling of mitochondrial adenosinetriphosphatase by 2-azidoadenosine 5'-[alpha-32P]diphosphate. 286 80

Phosphoenolpyruvate carboxylase from maize leaves was inactivated by pyridoxal 5'-phosphate in the dark and in the light. A two-step reversible mechanism is proposed for inactivation in the dark, which involves the formation of a noncovalent complex prior to a Schiff base with amino groups of the enzyme. Spectral analysis of pyridoxal 5'-phosphate-modified phosphoenolpyruvate carboxylase showed absorption maxima at 432 and 327 nm, before and after reduction with NaBH4, respectively, suggesting that epsilon-amino groups of lysine residues are the reactive groups in the enzyme. A correlation between spectral data and the maximal inactivation obtained with several concentrations of inhibitor allowed us to establish that the incorporation of 4 mol of pyridoxal 5'-phosphate per mole of holoenzyme accounts for total inactivation. The absence of modifier bound to phosphoenolpyruvate carboxylase when the modification was carried out in the presence of phosphoenolpyruvate and MgCl2 suggests the existence of an essential lysine residue at the catalytic site of the enzyme. Modification of phosphoenolpyruvate carboxylase in the light under an oxygen atmosphere resulted in an irreversible inactivation, which was completely protected by phosphoenolpyruvate and MgCl2. Spectral analysis of the photomodified enzyme showed an absorption peak of 320 nm, suggesting light-mediated addition of a nucleophilic residue (probably an imidazole group) to the pyridoxal 5'-phosphate-lysine azomethine bond.
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PMID:Modification of an essential amino group of phosphoenolpyruvate carboxylase from maize leaves by pyridoxal phosphate and by pyridoxal phosphate-sensitized photooxidation. 308 90

There are one or more proteins of 50,000 to 60,000 Mr in the thin filaments of insect flight muscle. A protein of 55,000 Mr has been isolated from insect fibrillar flight muscle and called arthrin. Despite its higher molecular weight, arthrin is in many ways like actin. The amino acid composition of arthrin was similar to that of actin. There were similarities in the peptides produced by digesting the denatured proteins and mild digestion of polymerized proteins cleaved similar-sized fragments from arthrin and actin. Polymerized arthrin activated the Mg2+ ATPase of myosin to the same extent as actin and the ATPase was regulated by rabbit or Lethocerus troponin and tropomyosin. Arthrin did not itself act as troponin-T. Electron microscopy of negatively stained specimens showed that arthrin and actin filaments were similar in structure and that arthrin could be decorated by rabbit subfragment-1 to form normal-looking arrowheads. Arthrin formed paracrystals at an optimum concentration of MgCl2 (25 mM) that was somewhat lower than the optimum for actin paracrystals. Optical diffraction showed that the structure of the paracrystals was similar to those formed from actin. The mass of arthrin and actin filaments relative to phage fd was measured by scanning transmission electron microscopy; the relative mass of arthrin and actin was 1.33, in agreement with molecular weight estimations. Therefore arthrin has the properties of a heavy form of actin. The proportion of actin, arthrin and troponin-T in Lethocerus myofibrils was six moles of actin to one mole of arthrin and one mole of troponin-T. The function of arthrin is not known.
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PMID:Arthrin: a new actin-like protein in insect flight muscle. 315 2

Bovine brain tubulin purified in the absence of GTP and MgCl2, reacts with 5'-p-fluorosulfonylbenzoylguanosine (5'-FSBG)2, an affinity analog of GTP and two moles of the reagent are incorporated per mole of tubulin at 0 degree C. 5'-FSBG is unable to promote the polymerization of tubulin into microtubules. 2 mM GTP, podophyllotoxin and vinblastine provide almost 50% protection against the modification, when added individually. Combination of these ligands gives maximal protection. Tubulin modified with 5'-FSBG lost two sulfhydryl groups per mole of tubulin and reduction with beta-mercaptoethanol led to the loss of the 2 moles of FSBG that had been incorporated. These data are interpreted on the basis that the modification of tubulin by 5'-FSBG proceeds via a thiosulfonate intermediate between the analogue and a reactive thiol group at or near that portion of the GTP binding site of tubulin where the phosphate moiety of GTP binds.
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PMID:Chemical modification of bovine brain tubulin with the guanine nucleotide affinity analogue 5'-p-fluorosulfonylbenzoylguanosine. 356 79

The effects of magnesium ions on the binding of the anticancer drug vinblastine to calf brain tubulin were investigated by a batch gel equilibration method. Magnesium ions at 1 mM strongly enhanced the binding of the first vinblastine molecule to each tubulin dimer without affecting either the drug affinity toward the rest of the binding site or the total stoichiometry of the vinblastine binding to tubulin. Sedimentation velocity studies indicated that magnesium ions can enhance strongly the vinblastine-induced tubulin self-association and suggested that the drug-induced self-association still proceeds through the isodesmic indefinite mechanism in the presence of the divalent cation. In PG buffer (0.01 M NaPi, 10(-4) M GTP, pH 7.0) containing more than 2.5 mM MgCl2, vinblastine induced tubulin to form large amorphous aggregates. The aggregate formation was rapid and took place at a drug stoichiometry between 0.7 and 1.0 mol of vinblastine per mole of tubulin dimers. Increasing the solution ionic strength decreased the rate of aggregate formation. Between an ionic strength of 0.05 and 0.1, the self-association led to the formation of paracrystalline aggregates instead of the amorphous ones. The results indicated that the binding of only the first vinblastine molecule to each tubulin dimer is linked to the self-association of the protein. They also confirmed our previously proposed rationale for the disagreement among the vinblastine-tubulin binding constants reported in the literature in terms of the different magnesium ion concentrations and ionic strength of the buffers used in the various studies.
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PMID:Interaction of vinblastine with calf brain tubulin: effects of magnesium ions. 379 May 19


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