[Prostaglandin H synthase. Chemical modification of histidine residues in various forms of the enzyme by diethylpyrocarbonate].

Prostaglandin H synthase (PGHS) as apo- and holoenzyme and the enzyme inactivated during the conversion of arachidonic acid into prostaglandin H2 has been modified by diethyl pyrocarbonate (DEPC). DEPC (40 mol/l mol protein) rapidly, but quantitatively differently interacted with the three forms of the enzyme (pH 6.0, 25 degrees C).

Prostaglandin H synthase. Inactivation of the enzyme in the course of catalysis is accompanied by fast and dramatic changes in protein structure.

Prostaglandin H synthase (PGHS) as apo-PGHS, holo-PGHS, and holo-PGHS, inactivated in the course of catalysis was studied using chemical modification with diethyl pyrocarbonate (DEPC). The exhausted reaction with DEPC corresponded to the modification of 7 histidine residues in apo-PGHS and 4 in holo-PGHS. All 18 histidine residues became accessible for modification with DEPC in the enzyme, inactivated in the course of catalysis.

[The effect of haptoglobin on prostaglandin H synthase from ram vesicular glands].

It was shown that the ability of sheep and horse haptoglobins differing in their immunological properties to inhibit PGH synthetase is about the same. It was found that haptoglobin inhibits the PGH synthetase-catalyzed enzymatic reaction, the inhibiting effect being non-competitive with respect to the electron donor, adrenaline. The degree of PGH synthetase inhibition by haptoglobin depends on the glycoprotein concentration, incubation time and enzyme activity.

[The effect of benzofurocaine on acute inflammation in rats and on the activity of prostaglandin synthetase in vitro].

Benzofurocaine similarly to ortophen (voltaren) causes dose-dependent suppression of acute inflammatory reactions induced in rats by carragheenin, serotonin and histamine, protects animals from absolutely lethal dose of cellulose sulphate. When administered in a dose of 0.79 X 10(-3) M, benzofurocaine exerts no effect on the activity of prostaglandin synthetase.

[Prostaglandin-like inhibitors of prostaglandin-H-synthase].

The effect of none prostaglandin-like cyclopentanone derivatives on the prostaglandin H synthase activity was studied. Seven substances proved to be inhibitors of the enzyme, some of the being similar to the well-known nonsteroid antiinflammatory drugs with respect to their inhibitory activity.

[Relation of the structure, rate of hydrolysis and activity of dicarboxylic acid esters].

The kinetics of enzymatic cholinesterase hydrolysis of dicarboxylic acid esters with neuromuscular blocking activity was studied in vitro. The maximum hydrolysis rate was shown to increase on elongation of the distance between ester groups both in the compounds containing a hydrophobic adamantyl radical attached to quaternary nitrogen and in bis-esters not containing adamantyl radicals. The comparison of neuromuscular blocking activity in vivo, enzymatic hydrolysis rates and activity on isolated skeletal muscle of some compounds demonstrated that in vivo activity is in a higher correlation with the maximum hydrolysis rate of the compounds that with activity in isolated skeletal muscle before or after cholinesterase inhibition.

[Hydrolysis by plasma cholinesterase of complex adamantyl-containing esters].

The kinetics of cholinesterase enzymatic hydrolysis of carboxylic acid adamantyl derivatives was studied in vitro. The maximal rate of enzymatic hydrolysis in the series of bis-esters was shown to increase on elongation of the distance between ester groups. The maximal hydrolysis rate in the series of bis- and mono-esters decreases on elongation of the distance between ester group and quaternary nitrogen atom.

[2-component inhibition of prostaglandin H synthetase by nonsteroidal anti-inflammatory preparations].

A combined effect on the irreversible inhibitor aspirin and fast reversible inhibitors ibuprofen, naproxen and sodium salicylate on prostaglandin-H-synthetase was studied on microsomal fractions from ram vesicular glands. The fast reversible inhibitors were shown to bind to prostaglandin-H-synthetase at the same site as aspirin and thereby to protect the enzyme against irreversible inactivation by aspirin.

[Nature of the interaction of voltaren and other pyrazolone and aniline derivatives with prostaglandin endoperoxide synthetase].

A study was made of the nature and mechanism of interaction of voltaren, butadion, analgin, phenacetin and paracetamol with endoperoxide prostaglandin synthetase (PGH-synthetase) of sheep vesicular glands. Activity of the enzyme was measured by polarography with the aid of a Clark's electrode. Butadion and analgin reversibly inhibited PGH-synthetase at concentrations of the order of 10(-4) M, whereas voltaren at those of the order of 10(-6) M.

[Mechanism of ibuprofen and naproxen interaction with endoperoxide prostaglandin synthetase].

The authors studied the pattern and mechanism of ibuprophen and naproxen interaction with endoperoxideprostaglandin synthetase (PGH synthetase) of sheep vesicular glands. The enzymatic activity of PGH synthetase was determined polarographically with the aid of a Clark electrode. Ibuprophen and naproxen were found to inhibit completely PGH synthetase at concentrations of the order of 1 X 10(-5) M.

[Mechanisms of interaction of acetylsalicylic acid and indomethacin with endoperoxide prostaglandin synthetase].

A study was made of the character and kinetics of interaction of acetylsalicylic acid and indomethacin with endoperoxide prostaglandin synthetase (PGH-synthetase) of sheep vesicular glands and human platelets. Enzymatic activity of PGH-synthetase was determined polarographically with the aid of Clark's electrodes. Acetylsalicylic acid was found to inhibit PGH-synthetase of sheep vesicular glands and human platelets at concentrations of the order of 1 x 10(-6) and 1 x 10(-4) M, whereas indomethacin at concentrations of 1 x 10(-6) and 1 x 10(-7) M, respectively.

[Effect of alcohols on the rate of cholinesterase decarbamoylation].

Butanol-1 and butandiol-1,4 are shown to increase the decarbamoylation rate of N-methylcarbamoyl- and N,N-dimethylcarbamoyl-cholinesterase. It is mainly due to the formation of a ternary complex NEA which is decomposed in 2,5 times faster than corbamoyl-enzyme EA. This is an evidence for the presence of some allosteric center in cholinesterase which is capable of binding alcohols.

[Effect of nucleophiles on the conversion of choline esters under the action of cholinesterase].

It is shown that effect of alcohols ROH on the hydrolysis of butyryl-choline and acetylcholine by choline esterase (E. C. 3.