Superefficient enzymes

Diffusion-controlled enzymes are characterized by second-order rate constants in the range 10(8)-10(10) M(-1)s(-1). These values are at the upper end of the observed rates of many enzyme-substrate reactions and have been predicted by theoretical studies on bimolecular reaction in solution. Such enzymes are considered to be perfect, since their rate-limiting step is not due to any chemical event but to the diffusional association rate between the enzyme and the substrate. Often the enzyme-substrate encounter is facilitated either through the presence of a strong attractive electric field, produced by charges on the enzyme surface, or through the reduction in the dimension of the search process. Here we provide a brief review of some of the enzymes characterized by a very fast second-order constant, focusing attention on triose phosphate isomerase and Cu,Zn superoxide dismutase taken as typical examples of such highly tuned enzymes.     

Determination of the kinetic parameters of enzyme inhibition of the K-type mechanism: application to the control of alpha-glucosidase activity of honeybee hemolymph by glucose]

The alpha-glucosidasic activity of emerging honeybees haemolymph is submitted to a feed-back inhibition by glucose, according to a mechanism of the "K" type (competitive). The "resulting affinity-constant" (measured in the presence of the enzyme both with substrate and inhibitor) is linear function of the inhibitor concentration. The affinity constants between enzyme and pure substrate on one hand, and between enzyme and pure inhibitor on the other hand, were determined by means of this relation, which led to respectively equivalent values after determinations under in vitro or in vivo inhibitions.     

Forecasting growth with time series models

This paper compares the structure of three models for estimating future growth in a time series. It is shown that a regression model gives minimum weight to the last observed growth and maximum weight to the observed growth in the middle of the sample period. A first-order integrated ARIMA model, or 1(1) model, gives uniform weights to all observed growths. Finally, a second-order integrated ARIMA model gives maximum weights to the last observed growth and minimum weights to the observed growths at the beginning of the sample period. The forecasting performance of these models is compared using annual output growth rates for seven countries.     

MAO inhibition,an unlikely mode of action for chlordimeform

Summary Inhibition constants of several formamidines, their corresponding formanilides and other representatives of compounds derived from aniline, such as phenylureas, N-phenyl-carbamates and acylanilides, were determined for rat liver monoamine oxidase. The reversability of the inhibition and the lack of correlation between inhibition potencies and toxicities of the compounds tested add to the opinion that MAO inhibition is not a prominent factor in chlordimeform poisoning.     

Correlations between glucose-inhibition and control parameters of α-glucosidase kinetics inApis mellifica haemolymph (Hymenoptera: Insecta)

Summary Kinetics studies of haemolymph -glucosidase inhibition by D. glucose led to general correlations between inhibition and control parameters, all over the honeybee development. Maximum velocities are not affected by the inhibition, while affinity constants are always significantly increased, and Hill coefficients tend to decrease, especially in foraging adults and in prenymphs. In this later case, the n-type effect tends to break the manifestation of the K-type mechanism.     

Glucosamine enhanced sperm-egg binding but inhibited sperm-egg fusion in mouse

In order to study the sperm-egg recognition mechanism on the surface of the plasma membrane, zonae were removed from mouse eggs by exposure to acidic conditions. Sperm binding to denuded eggs was then observed in the presence of various sugars. Among several carbohydrates tested, only glucosamine (GlcN) was found to increase the number of sperm bound to eggs while inhibiting sperm-egg fusion. The inhibition was reversible; when denuded eggs were transferred to a GlcN free medium, a high rate of polyspermy was observed.     

Hemmungswirkung verschiedener Chinone auf die Eiweißspaltung durch Papain

Summary With the intention to clarify the mechanism of action of the antibiotic effect of some quinones the inhibition of the activity of papain by various quinones was measured. The results let it appear improbable that there is any relation between the antibacterial effect of the quinones and their inhibition power on papain. On the other hand a close parallelism was found in the strength of inhibition of the same quinones on papain, urease and catalase. The mechanism of action of the quinone inhibition of these three enzymes must be regarded as a very similar one.

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Ausführliche Veröffentlichung mit weiteren Belegen folgt in den Monatsheften für Chemie (Wien).     

Naloxone and intestinal motility

Summary It was supposed that the inhibition of intestinal peristalsis seen in animals and humans after abdominal surgery might be related to the release of endorphins, endogenous opiate receptor agonists, caused by the surgical stress and pain. However, naloxone, a potent morphine and endorphin antagonist, failed to block this peristaltic inhibition in rats, which leaves the mechanism of this inhibition, and thus the function of intestinal endorphins, still very much in doubt.     

Naloxone and intestinal motility.

It was supposed that the inhibition of intestinal peristalsis seen in animals and humans after abdominal surgery might be related to the release of endorphins, endogenous opiate receptor agonists, caused by the surgical stress and pain. However, naloxone, a potent morphine and endorphin antagonist, failed to block this peristaltic inhibition in rats, which leaves the mechanism of this inhibition, and thus the function of intestinal endorphins, still very much in doubt.     

Inhibition of thiamine transport in baker's yeast by methylene blue

Summary Methylene blue was found to inhibit thiamine transport competitively (K_i=0.63 M) in baker's yeast. The dye was also effective in abolishing the growth inhibition ofSaccharomyces cerevisiae by pyrithiamine which is known to be taken up by a common transport system for thiamine in yeast cells. A possible mechanism for the inhibition by methylene blue of the thiamine transport system in baker's yeast is discussed.     

Irreversible synthetische inhibitoren der Urokinase

Summary Urokinase, the plasminogen activator from urine, is inhibited irreversibly by diisopropyl fluorophosphate and 4-nitrobenzyl 4-guanidinobenzoate. The reactions of inhibition underlie pseudofirst-order kinetics. Rate constants were estimated. Urokinase is not inactivated by incubation with tosyl-l-lysine chloromethyl ketone.     

农业立体污染综合防治研究的概况与进展

概述了国内外农业污染防治研究领域的历史与现状,阐明了农业污染防治新思路,即农业立体污染综合防治路线与措施,并进一步对农业立体污染综合防治的高效投入机制和集成创新模式进行了深入分析。     

Mitotic inhibition of clathrin-mediated endocytosis

Endocytosis and mitosis are fundamental processes in a cell’s life. Nearly 50 years of research suggest that these processes are linked and that endocytosis is shut down as cells undergo the early stages of mitosis. Precisely how this occurs at the molecular level is an open question. In this review, we summarize the early work characterizing the inhibition of clathrin-mediated endocytosis and discuss recent challenges to this established concept. We also set out four proposed mechanisms for the inhibition: mitotic phosphorylation of endocytic proteins, altered membrane tension, moonlighting of endocytic proteins, and a mitotic spindle-dependent mechanism. Finally, we speculate on the functional consequences of endocytic shutdown during mitosis and where an understanding of the mechanism of inhibition will lead us in the future.     

The effectiveness of imprecise probability forecasts

In this paper we investigate the feasibility of algorithmically deriving precise probability forecasts from imprecise forecasts. We provide an empirical evaluation of precise probabilities that have been derived from two types of imprecise probability forecasts: probability intervals and probability intervals with second-order probability distributions. The minimum cross-entropy (MCE) principle is applied to the former to derive precise (i.e. additive) probabilities; expectation (EX) is used to derive precise probabilities in the latter case. Probability intervals that were constructed without second-order probabilities tended to be narrower than and contained in those that were amplified by second-order probabilities. Evidence that this narrowness is due to motivational bias is presented. Analysis of forecasters' mean Probability Scores for the derived precise probabilities indicates that it is possible to derive precise forecasts whose external correspondence is as good as directly assessed precise probability forecasts. The forecasts of the EX method, however, are more like the directly assessed precise forecasts than those of the MCE method.     

Inhibition of in vitro RNA synthesis by hycanthone,oxamniquine and praziquantel

Summary The schistosomicides, hycanthone, oxamniquine and praziquantel, were found to inhibit the in vitro RNA synthesis using isolated hamster liver nuclei. Preincubation of the nuclei with these drugs revealed that the inhibitory effect of oxamniquine was irreversible and progressed with time, whereas that of hycanthone and parziquantel was reversible. On the other hand, hycanthone and praziquantel have a high affinity for DNA but oxamniquine does not. The data indicate that the mechanism of inhibition by oxamniquine is different from that of hycanthone and praziquantel.     

Heparin inhibition of the antithrombin activity of alpha-2-macroglobulin]

The interaction between thrombin and alpha-2-macroglobulin was studied on human purified materials, either in the presence or in the absence of heparin, by kinetic analysis of thrombin inhibition and polyacrylamide gel electrophoresis. In the absence of heparin, binding of thrombin to alpha-2-macroglobulin, shown by electrophoresis, leads to the loss of the coagulant property of the enzyme. In the presence of heparin the rate of inhibition of thrombin clotting activity by alpha-2-macroglobulin is strongly decreased. Heparin binds to thrombin, impairing the formation of thrombin-alpha-2-macroglobulin complex. These data show that heparin paradoxically protects thrombin from inhibition by alpha-2-macroglobulin whereas it increases the enzyme inhibition by antithrombin III. Such a phenomenon could be of practical interest for treatment of thrombosis in patients with high plasma level of alpha-2-macroglobulin and low level of antithrombin III, such as occurs in the nephrotic syndrome.     

Inhibition of in vitro RNA synthesis by hycanthone, oxamniquine and praziquantel.

The schistosomicides, hycanthone, oxamniquine and praziquantel, were found to inhibit the in vitro RNA synthesis using isolated hamster liver nuclei. Preincubation of the nuclei with these drugs revealed that the inhibitory effect of oxamniquine was irreversible and progressed with time, whereas that of hycanthone and praziquantel was reversible. On the other hand, hycanthone and praziquantel have a high affinity for DNA but oxamniquine does not. The data indicate that the mechanism of inhibition by oxamniquine is different from that of hycanthone and praziquantel.     

The effect of ion pair formation on the antimuscarinic activity of methantheline.

The quaternary ammonium compound, methantheline, was found to antagonize acetylcholine induced contractions in isolated guinea pig ileum by a mechanism which did not conform to the criteria for either competitive or non-competitive inhibition. Enhancement of the lipid solubility of methantheline by formation of an ion pair with trichloracetate failed to influence its cholinergic inhibitory activity. The results suggest that in the guinea pig ileum a) an intracellular site of action does not exist for methantheline and b) the membrane receptors for methantheline most likely are located in an aqueous environment.     

Characterization of the partial inhibition, by deficiency in serum factors, of multiplication of SV3T3 transformed fibroblasts]

Partial inhibition, by serum starvation, of multiplication of SV3T3 transformed fibroblasts was studied by cultivating cells in a medium containing 1% of serum. Two different and successive states are described: a first step, with a rate of multiplication for 24 hrs, which is lowered (2 instead of 3 in a normal medium containing 10% of serum) but which remains constant (i.e. exponential multiplication), the observed inhibition being reversed by normal medium; a second step, where the rate of multiplication for 24 hrs, decreases very fast, and which is not reversible.