KINETICS FOR THE INHIBITION OF CARBOXYLESTERASE BY MALAOXON

1967 ◽  
Vol 45 (6) ◽  
pp. 757-771 ◽  
Author(s):  
A. R. Main ◽  
W. C. Dauterman
Keyword(s):  
Rat Liver ◽  
Rate Constants ◽  
Direct Evidence ◽  
The Other ◽  
Velocity Constant ◽  
Irreversible Inhibition ◽  
Inhibition Reaction ◽  
Phosphorylation Rate

Malaoxon and carboxylesterase undergo two separate but simultaneous reactions when mixed in solution. One results in the irreversible inhibition of carboxylesterase. In the other, malaoxon acts as a substrate and is hydrolyzed.This work is concerned primarily with the inhibition reaction, although direct evidence of the substrate reaction is also given. It seemed possible that inhibition could occur by two mutually exclusive routes. Equations were derived for each of the two routes, and both equations gave identical and unambiguous expressions for ki, the bimolecular velocity constant of the inhibition reaction. A procedure for determining the kivalues of malaoxon and of four carboalkoxy homologues of malaoxon in reaction with partially purified rat-liver carboxylesterase is described. Evidence is given which suggested that the substrate reaction was controlled by the acylation step. This in turn suggested that useful estimates of the binding (Ka) and phosphorylation rate constants (k2p) could be made. Values for kiand tentative values for k2pand Kaare given.

scholarly journals The stereochemical course of phosphoryl transfer catalysed by glucokinase.

1982 ◽  
Vol 201 (2) ◽  
pp. 421-423 ◽  
Author(s):  
D Pollard-Knight ◽  
B V L Potter ◽  
P M Cullis ◽  
G Lowe ◽  
A Cornish-Bowden
Keyword(s):  
Rat Liver ◽  
Rate Constants ◽  
Ternary Complex ◽  
The Other ◽  
Chemical Mechanism ◽  
Phosphoryl Group ◽  
Phosphoryl Transfer ◽  
Reaction Proceeds ◽  
Gamma S ◽  
Yeast Hexokinase

Adenosine 5'-[gamma(S)-16O,17O,18O]triphosphate has been used to determine the stereo-chemical course of phosphoryl transfer catalysed by rat liver glucokinase. The chirality of the product, D-glucose 6-[16O,17O,18O]phosphate was analysed by 31P n.m.r. spectroscopy. The reaction proceeds with inversion of configuration at phosphorus. The simplest interpretation of this result, which is the same as that observed with yeast hexokinase [Lowe & Potter (1981) Biochem. J. 199, 277-233], is that the phosphoryl group is transferred between MgATP2- and glucose in the ternary complex by an ‘in-line’ mechanism. It accords with the veiw that the kinetic differences between glucokinase and the other hexokinases arise from differences in rate constants and not from any fundamental differences in chemical mechanism.

Methylene. III. Gas phase reactions with 1-chloropropane

1969 ◽  
Vol 312 (1509) ◽  
pp. 141-161 ◽  
Keyword(s):  
Gas Phase ◽  
Rate Constants ◽  
Hydrogen Abstraction ◽  
The Other ◽  
Gas Phase Reactions ◽  
Other Hand ◽  
Chlorine Substituent ◽  
High Degree ◽  
Singlet Methylene

The work described in this and the following paper is a continuation of that in parts I and II, devoted to elucidation of the mechanism of the reactions of methylene with chloroalkanes, with particular reference to the reactivities of singlet and triplet methylene in abstraction and insertion processes. The products of the reaction between methylene, prepared by the photolysis of ketene, and 1-chloropropane have been identified and estimated and their dependence on reactant pressures, photolysing wavelength and presence of foreign gases (oxygen and carbon mon­oxide) has been investigated. Both insertion and abstraction mechanisms contribute significantly to the over-all reaction, insertion being relatively much more important than with chloroethane. This type of process appears to be confined to singlet methylene. If, as seems likely, there is no insertion into C—Cl bonds under our conditions (see part IV), insertion into C2—H and C3—H bonds occurs in statistical ratio, approximately. On the other hand, the chlorine substituent reduces the probability of insertion into C—H bonds in its vicinity. As in the chloroethane system, both species of methylene show a high degree of selectivity in their abstraction reactions. We find that k S Cl / k S H >7.7, k T Cl / k T H < 0.14, where the k ’s are rate constants for abstraction, and the super- and subscripts indicate the species of methylene and the type of atom abstracted, respectively. Triplet methylene is discriminating in hydrogen abstraction from 1-C 3 H 7 Cl, the overall rates for atoms attached to C1, C2, C3 being in the ratios 2.63:1:0.

scholarly journals The fractionation of nuclei from mammalian cells by zonal centrifugation

1968 ◽  
Vol 109 (1) ◽  
pp. 127-135 ◽  
Author(s):  
I R Johnston ◽  
A P Mathias ◽  
F. Pennington ◽  
D. Ridge
Keyword(s):  
Rat Liver ◽  
Mammalian Cells ◽  
Mouse Liver ◽  
The Other ◽  
Slow Speed ◽  
Adult Rats ◽  
Sucrose Solutions ◽  
Liver Nuclei ◽  
Effect Of Age ◽  
Zonal Rotor

1. Purified liver nuclei from adult rats separate into two main zones when centrifuged in the slow-speed zonal rotor. One zone contains diploid nuclei, the other tetraploid. 2. The effect of age on the pattern of rat liver ploidy was examined. Tetraploid nuclei are virtually absent from young animals. They increase in proportion steadily with age. Partial hepatectomy disturbs the pattern of ploidy. 3. The zonal centrifuge permits the separation of diploid, tetraploid, octaploid and hexadecaploid nuclei from mouse liver. 4. Rat liver nuclei are isopycnic with sucrose solutions of density 1·35 at 5°.

The Origins of Domestic Sheep and Goats: a Reconsideration in the Light of the Fossil Evidence

1969 ◽  
Vol 34 ◽  
pp. 368-384 ◽  
Author(s):  
Sebastian Payne
Keyword(s):  
Direct Evidence ◽  
Present Situation ◽  
Wild Relatives ◽  
The Other ◽  
Domestic Sheep ◽  
Sheep And Goats ◽  
Animal Domestication ◽  
The Past ◽  
The One ◽  
And Control

In recent discussions of the origins and process of animal domestication (Reed, 1961, Zeuner, 1963), both authors rely on two kinds of evidence: on the one hand, the present distributions and characteristics of the different breeds of whatever animal is being discussed, together with its feral and wild relatives, and, on the other hand, the past record, given by literary and pictorial sources and the bones from archaeological and geological sites. Increased recognition of the limitations of the past record, whether in the accuracy of the information it appears to give (as in the case of pictorial sources), or in the certainty of the deductions we are at present capable of drawing from it (this applies especially to the osteological record), has led these authors to argue mainly from the present situation, using the past record to confirm or amplify the existing picture.Arguing from the present, many hypotheses about the origins and process of domestication are available. The only test we have, when attempting to choose between these, lies in the direct evidence of the past record. The past record, it is freely admitted, is very fragmentary: the information provided by the present situation is more exact, ranges over a much wider field, and is more open to test and control. Nevertheless, the past record, however imperfect it is, is the only direct evidence we have about the process of domestication.

scholarly journals Loss of haem in rat liver caused by the porphyrogenic agent 2-allyl-2-isopropylacetamide

1971 ◽  
Vol 124 (4) ◽  
pp. 767-777 ◽  
Author(s):  
F. De Matteis
Keyword(s):  
Rat Liver ◽  
Microsomal Fraction ◽  
Direct Evidence ◽  
Gradual Increase ◽  
Rapid Loss ◽  
Metabolizing Enzymes ◽  
Liver Microsomal Fraction ◽  
Green Pigments ◽  
Cytochrome P 450 ◽  
Increased Activity

1. The effect of a single dose of 2-allyl-2-isopropylacetamide on the cytochrome P-450 concentration in rat liver microsomal fraction was studied. The drug caused a rapid loss of cytochrome P-450 followed by a gradual increase to above the normal concentration. 2. The loss of cytochrome P-450 was accompanied by a loss of microsomal haem and by a brown–green discoloration of the microsomal fraction suggesting that a change in the chemical constitution of the lost haem had taken place. Direct evidence for this was obtained by prelabelling the liver haems with radioactive 5-aminolaevulate: the drug caused a loss of radioactivity from the haem with an increase of radioactivity in a fraction containing certain un-identified green pigments. 3. Evidence was obtained by a dual-isotopic procedure that rapidly turning-over haem(s) may be preferentially affected. 4. The loss of cytochrome P-450 as well as the loss of microsomal haem and the discoloration of the microsomal fraction were more intense in animals pretreated with phenobarbitone and were much less evident when compound SKF 525-A (2-diethylaminoethyl 3,3-diphenylpropylacetate) was given before 2-allyl-2-isopropylacetamide, suggesting that the activity of the drug-metabolizing enzymes may be involved in these effects. 5. The relevance of the destruction of liver haem to the increased activity of 5-aminolaevulate synthetase caused by 2-allyl-2-isopropylacetamide is discussed.

scholarly journals Ganglioside incorporation and release by the isolated perfused rat liver

1991 ◽  
Vol 274 (2) ◽  
pp. 581-585 ◽  
Author(s):  
S C Kivatinitz ◽  
A Miglio ◽  
R Ghidoni
Keyword(s):  
Rat Liver ◽  
The Other ◽  
Regulatory Role ◽  
Isolated Perfused Rat Liver ◽  
Order Kinetic ◽  
Perfused Rat Liver ◽  
Ganglioside Gm1 ◽  
First Order ◽  
Pseudo First Order

The fate of exogenous ganglioside GM1 labelled in the sphingosine moiety, [Sph-3H]GM1, administered as a pulse, in the isolated perfused rat liver was investigated. When a non-recirculating protocol was employed, the amount of radioactivity in the liver and perfusates was found to be dependent on the presence of BSA in the perfusion liquid and on the time elapsed after the administration of the ganglioside. When BSA was added to the perfusion liquid, less radioactivity was found in the liver and more in the perfusate at each time tested, for up to 1 h. The recovery of radioactivity in the perfusates followed a complex course which can be described by three pseudo-first-order kinetic constants. The constants, in order of decreasing velocity, are interpreted as: (a) the dilution of the labelled GM1 by the constant influx of perfusion liquid; (b) the washing off of GM1 loosely bound to the surface of liver cells; (c) the release of gangliosides from the liver. Process (b) was found to be faster in the presence of BSA, probably owing to the ability of BSA to bind gangliosides. The [Sph-3H]GM1 in the liver underwent metabolism, leading to the appearance of products of anabolic (GD1a, GD1b) and catabolic (GM2, GM3) origin; GD1a appeared before GM2 and GM3 but, at times longer than 10 min, GM2 and GM3 showed more radioactivity than GD1a. At a given time the distribution of the radioactivity in the perfusates was quite different from that of the liver. In fact, after 60 min GD1a was the only metabolite present in any amount, the other being GM3, the quantity of which was small. This indicates that the liver is able to release newly synthesized gangliosides quite specifically. When a recirculating protocol was used, there were more catabolites and less GD1a than with the non-recirculating protocol. A possible regulatory role of ganglioside re-internalization on their own metabolism in the liver is postulated.

Abnormal vascular function and morphology in preeclampsia: a study of isolated resistance vessels

1985 ◽  
Vol 69 (4) ◽  
pp. 477-482 ◽  
Author(s):  
C. Aalkjaer ◽  
H. Danielsen ◽  
P. Johannesen ◽  
E. B. Pedersen ◽  
A. Rasmussen ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Pregnant Women ◽  
Vascular Function ◽  
Direct Evidence ◽  
The Other ◽  
Vascular Changes ◽  
Direct Information ◽  
Vascular Abnormalities ◽  
Media Thickness ◽  
Resistance Vessels

1. In order to obtain direct information about vascular changes associated with pre-eclampsia, the morphological and functional characteristics of isolated omental resistance vessels from 11 women with pre-eclampsia, 10 normotensive pregnant women and eight normotensive nonpregnant women were determined. 2. In vessels from the women with preeclampsia, the ratio of media thickness to lumen diameter was increased, compared with that in vessels from the other two groups. 3. The vessels from the women with preeclampsia had an increased responsiveness to angiotensin II and a decreased rate of relaxation, but only when compared with the vessels from the normotensive pregnant women. However, no difference in responsiveness to noradrenaline was found between any of the groups. 4. The angiotensin II responsiveness of the vessels from the women with pre-eclampsia and from the non-pregnant women were similar, suggesting that pre-eclampsia is associated with an absence of the change in vascular function which normally occurs during pregnancy. 5. The study provides direct evidence for an involvement of vascular abnormalities in the pathogenesis of pre-eclampsia.

Photoreceptor coupling in turtle retina

1998 ◽  
Vol 15 (4) ◽  
pp. 755-764 ◽  
Author(s):  
M.L. FIRSOV ◽  
D.G. GREEN
Keyword(s):  
Receptive Field ◽  
Gap Junctions ◽  
Direct Evidence ◽  
Physiological Responses ◽  
The Other ◽  
Morphological Data ◽  
Chelydra Serpentina ◽  
Intracellular Injection ◽  
Coupled Cells ◽  
High Degree

Photoreceptors in the isolated turtle retina of two species of turtle, Chelydra serpentina and Pseudemus scripta elegans, were penetrated with double-barrel electrodes. Physiological responses were recorded through one barrel and Neurobiotin tracer was injected from the other. Intracellular injection of Neurobiotin revealed patterns of tracer-coupled photoreceptors. Both the patterns of tracer coupling and the electrophysiology suggest a high degree of specificity of connections. Rods seem to be coupled only to rods and green and red cones seem to be coupled to cones of the same spectral type. Receptive-field profiles, measured with a thin, sharply focused slit of light, often had well-defined peaks and troughs in sensitivity. We have taken advantage of this observation and used the position of a peak in sensitivity to locate the position on the retina of a coupled cell. In one rod, it was possible to correlate physiological and morphological data and to show that the peaks in the physiological receptive field occurred at positions on the retina where there were dye-coupled cells. This provides direct evidence that gap junctions produce the physiological coupling between rods.

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