Inhibition of pig-heart citrate synthase by carboxylic acids structurally related to oxaloacetate.
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Acetyl Coenzyme A↗
Biomedical subjects
G Pettersson
Publications and source records attributed to G Pettersson.
Total small bowel strangulation: a case report.
A case of strangulation of the entire small intestine caused by an internal incarcerated hernia is presented. At laparotomy the small intestine was severely discoloured, paralytic and the viability of the bowel was questionable. No resection was performed. At a second laparotomy 10 h later the intestine was hyperaemic and exhibited lively motor activity. Recovery was complete. The importance of prolonged conservative management in avoiding extensive resection is stressed.
Adult↗
The effects of splanchnic nerve stimulation on the plasma levels of serotonin and substance P in the portal vein of the cat.
The blood levels of serotonin (5-HT) and substance P (SP) in the portal vein were studied after splanchnic nerve stimulation in the cat. The portal levels of both substances were studied before, during and after splanchnic nerve stimulation. There was a twofold increase in 5-HT during stimulation whilst the SP concentration remained unchanged. These results suggest that the nervous control of the amine release into the portal stream and the mechanism that regulates the release of the polypeptide is not the same.
Animals↗
Effect of pH on coenzyme binding to liver alcohol dehydrogenase.
1. The transient-state kinetics of ligand-displacement reactions have been analyzed. Methods based on this analysis have been used to obtain reliable estimates of on-velocity and off-velocity constants for coenzyme binding to liver alcohol dehydrogenase at different pH values between 6 and 10. 2. The rate of NADH dissociation from the enzyme shows no pronounced dependence on pH. The rate of NAD+ dissociation is controlled by a group with a pKa of 7.6, agreeing with the pKa reported to regulate the binding of certain inhibitory substrate analogues to the enzyme . NAD+ complex. 3. Critical experiments have been performed to test a recent proposal that on-velocity constants for the binding of NADH and NAD+ are controlled by proton equilibria exhibiting different pKa values. The results show that association rates for NADH and NAD+ exhibit the same pH dependence corresponding to a pKa of 9.2. Titrimetric evidence is presented indicating that the latter effect of pH derives from ionization of a group which affects the anion-binding capacity of the coenzyme-binding site.
Alcohol Oxidoreductases↗
The effect of transmural field stimulation on the serotonin content in rat duodenal enterochromaffin cells--in vitro.
The effect of transmural field stimulation (TFS)--in vitro--on the sertonin (5-HT) content in enterochromafffin cells (EC) in rat duodenum was studied with a cytofluorimetric method. TFS caused a significant 25% decrease of 5-HT in EC. The presence of tetrodotoxin or d,1-propranolol in the stimulation bath antagonized the effect of TFS. In biopsies from rats pretreated with 6-OH-dopamine TFS had no effect of the 5-HT content in EC. The results of the present study strongly suggest, that the TFS induced decrease in 5-HT content is due to a direct neural, probably beta-adrenoceptor mediated, influence on the EC.
Adrenergic Fibers↗
The effect of propranolol on the serotonin concentration in the portal plasma after vagal nerve stimulation in the cat.
Efferent cervical vagal nerve stimulation in the cat caused a marked increase of the portal plasma 5-HT concentration. This increase was more than two-fold within 15 min of stimulation. After cessation of stimulation portal plasma 5-HT returned to basal levels within 10 min. Treatment with the beta-adrenoceptor antagonist propranolol, in various doses (0.1-2 mg/kg b.wt.), did not abolish but significantly reduced the response to vagal stimulation, particularly during the final part of the stimulation period. The results confirm the existence of a beta-adrenoceptor-mediated release of 5-HT, but also suggest that other mechanisms for 5-HT release may be involved in the response on vagal nerve stimulation.
Adrenergic beta-Antagonists↗
The neural control of the serotonin content in mammalian enterochromaffin cells.
Serotonin (5-HT) in the mammalian gut is mainly stored in enterochromaffin cells (EC). Vagal or splanchnic nerve stimulation respectively increase portal blood levels of 5-HT and decrease 5-HT content in EC, suggesting a neural control of these cells. Previous studies have also suggested that the vagal effect is mediated via vagal adrenergic nerve fibers, since this effect could be blocked by sympathectomy, removal of the superior cervical sympathetic ganglia or by the administration of a beta-adrenoceptor blocking agent, d, 1-propranolol. In the present study the control of the 5-HT content in EC was studied by a cytofluorimetric method in specimens from rat duodenal mucosa after drug incubations and transmural field stimulation (TFS) in vitro: Incubations in a Krebs' solution containing adrenaline (A), noradrenaline (NA) or isoprenaline (IP) (10(-9)--10(-5) M) caused a decrease of the 5-HT content in EC. For NA and A this effect was concentration-dependent. The effect of A was antagonized by d, 1-propranolol but not by d-propranolol, metoprolol, phentolamine or phenoxybenzamine. This indicates that the effects observed were mediated via a true beta-adrenoceptor mechanism. Acetylcholine (ACh), in the presence of eserine, also decreased the 5-HT content in EC, but was less potent than the adrenergic substances. TFS decreased the 5-HT content of EC to about 75% of unstimulated control levels. The presence of tetrodotoxin or d, 1-propranolol in the stimulation bath antagonized the effect of TFS. In specimens from rats pretreated with 6-OH-dopamine, TFS had no effect. Thus, TFS appears to induce a release of 5-HT from EC mainly by activation of adrenergic nerves. The ultrastructural relationship between nerve terminals and EC was studied in the guinea-pig duodenum. Animals were pretreated with 5-OH-dopamine in order to visualize adrenergic nerves. Near the base of most of the EC examined, at least 3 different types of nerve terminals were observed with the appearance of adrenergic, cholinergic and peptidergic terminals. In addition, dendrite-like processes were demonstrated. No true synapse on EC was found, but the minimal distance between the nerve terminals and EC was 150-250 nm, well within the limits of the "autonomic gap", suggesting a functional neural influence on these cells. The importance of the demonstrated beta-adrenergic control of EC was further studied in vivo. Efferent vagal nerve stimulation in the cat caused increased 5-HT levels in the portal plasma to more than twice the normal values after 15 min stimulation. Administration of the beta-adrenoceptor antagonist d, 1-propranolol in various doses did not abolish, but significantly reduced the response, particularly during the final part of the stimulation period. These results not only confirm a beta-adrenoceptor mediated release of 5-HT, but also suggest that other mechanisms are involved in the total response to vagal nerve stimulation.
Acetylcholine↗
Substance P-, VIP-, and enkephalin-like immunoreactivity in the human vagus nerve.
The human vagus nerve has been investigated for the presence of substance P (SP), vasoactive intestinal polypeptide (VIP), and enkephalin (ENK) using immunohistochemistry. After 0.5-4 hr of nerve ligation during surgical operations two right thoracic main truncs, two anterior subdiaphragmal trunks, and four anterior nerves of Latarjet were found to contain accumulation of immunoreactive material in nerve fibers above the ligation. Very high numbers of SP-, medium numbers of ENK-, and low number of VIP-immunoreactive fibers were seen. The relative proportions were similar at all levels studied. These data thus indicate the presence and axonal transport of SP-, ENK-, and VIP-like peptides in the human vagus nerve. Our observations in humans correlate well with results obtained from other species. Thus gastrointestinal vagal sensory mechanisms may be mediated by SP (and possibly VIP) and some motor mechanisms by ENK.
Endorphins↗
Changes in the copper centres of benzylamine oxidase from pig plasma during the catalytic cycle.
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Animals↗
Effect of pH on the process of ternary-complex interconversion in the liver-alcohol-dehydrogenase reaction.
1. Kinetic relationships referring to multiple-turnover conditions have been derived for the slowest exponential transient appearing in two-substrate enzyme reactions proceeding by an ordered ternary-complex mechanism. The validity of these and previously derived theoretical relationships for this mechanism has been tested by application to the liver alcohol dehydrogenase reaction. 2. All essential features of the transient-state kinetics of alcohol oxidation by NAD+ in the liver alcohol dehydrogenase system can be qualitatively and quantitatively explained in view of the compulsory-order mechanism in the proposed scheme. There is no kinetic evidence for any half-of-the-sites reactivity of the enzyme. A consistent set of rate constants is reported for the enzymic oxidation of benzyl alcohol at pH 8.75. 3. Transient-state rate parameters for benzyl alcohol/benzaldehyde catalysis by liver alcohol dehydrogenase have been determined at different pH. The interpretation of such rate parameters is critically discussed with reference to their informative value for the purpose of determination of rate constants (k and k') for the process of ternary-complex interconversion in the proposed scheme. It is concluded that the apparent rate constant (k') for hydride transfer from benzyl alcohol to NAD+ is dependent on a proton dissociation step with a pKa of 6.4, whereas the rate constant (k) for hydride transfer from NADH to benzaldehyde exhibits no corresponding dependence on proton association. 4. The asymmetric pH dependence of the forward and reverse rate of ternary-complex interconversion during liver alcohol dehydrogenase catalysis appears to reflect an obligatory step of alcohol/alcoholate ion equilibration occurring at the ternary-complex level. It is suggested that the observed pKa 6.4 dependence of the transient rate of alcohol oxidation can be attributed to a coupled acid-base system involving minimally the enzyme-bound alcohol and the protein residues Ser-48 and His-51.
Alcohol Oxidoreductases↗
Purification and characterization of a low molecular weight 1,4-beta-glucan glucanohydrolase from the cellulolytic fungus Trichoderma viride QM 9414.
A low molecular weight 1,4-beta-glucan glucanohydrolase (endoglucanase) (1,4-(1,3;1,4)-beta-D-glucan 4-glucanohydrolase, EC 3.2.1.4) has been isolated from culture filtrates of the fungus Trichoderma viride QM 9414 by a two-step procedure of gel filtration and ion-exchange chromatography. The isolated enzyme appeared homogeneous upon polyacrylamide gel electrophoresis at pH 2.9, isoelectric focusing in a polyacrylamide gel slab, sedimentation equilibrium analysis and chromatography of the reduced and alkylated enzyme on a column of Sepharose 6B in 6 M guanidine - HCl. A molecular weight was calculated at approx. 20 000 and the isoelectric point was determined at pH 7.52. The purified enzyme was not a carbohydrate-containing protein.
Amino Acids↗
Effects on enzyme activity of ligand-binding to copper in pig-plasma benzylamine oxidase.
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Animals↗
The order of substrate addition and product release during the catalytic action of pig-plasma benzylamine oxidase.
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Ammonia↗
Active-site titration of pig-plasma benzylamine oxidase.
1. Titration of benzylamine oxidase with benzylamine under anaerobic conditions shows that full reduction of the enzymic 470-nm chromophore is obtained on the addition of one mole of substrate per mole of enzyme. Concomitantly, one mole of benzaldehyde per mole of enzyme is produced. 2. A single prosthetic group interacting with carbonyl reagents can be detected on titration of benzylamine oxidase with phenylhydrazine. Titration data reported to indicate a higher content of prosthetic groups were obtained under conditions where equilibration between enzyme and phenylhydrazine is insufficiently complete. 3. It is concluded that pig-plasma benzylamine oxidase contains a single catalytically active site. This means that the two copper atoms present in the enzyme may be structurally or functionally different.
Anaerobiosis↗
Evidence for innervation of the small intestine from the cervical sympathetic ganglia.
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Adrenergic Fibers↗
The release of serotonin from rat duodenal enterochromaffin cells by adrenoceptor agonists studied in vitro.
The serotonin (5-HT) content of enterochromaffin cells (EC) was studied by a cytofluorimetric method in biopsies from rat duodenal mucosa after in vitro incubation with different adrenoceptor agonists and antagonists and acetylcholine (ACh). Noradrenaline (NA), Adrenaline (A) and Isoprenaline (IP) caused a decrease of 5-HT in EC down to 40--60% and for NA and A this effect was concentration-dependent. The effect was antagonized by d,1-propranolol but not by d-propranolol, metoprolol, phentolamine or phenoxybenzamine indicating that the 5-HT release from EC is probably mediated via a true beta-adrenoceptor mechanism possibly of the beta2 type. ACh also decreased the 5-HT content of EC but was much less potent than the adrenergic substances. Dopamine (DA) had no effect.
Acetylcholine↗
Ultrastructural evidence for an innervation of epithelial enterochromaffine cells in the guinea pig duodenum.
The innervation of the duodenal enterochromaffine cells (E.C.) of the guinea pig was studied at the electronmicroscopic level. Pretreatment with 5-OH-dopamine was performed to visualize catecholaminergic (CA) nervous elements. Near the basement membrane of all examined E.C. in the crypts, bundles of unmyelinated nerve processes were observed, only partly ensheathed in a Schwann cell cover. At least 4 types of processes could be observed. 1) Boutons containing only small clear vesicles, probably cholinergic fibres; 2) boutons with small clear vesicles, and in addition large (greater than 200 nm) granules with a dense matrix (P-type-fibres); 3) boutons with small electron-dense vesicles, probably CA-fibres; and 4) processes with few vesicles but having the appearance of dendrites. No typical synaptic arrangements were observed, but the minimal distance between the E.C. and the nerve bundles was 150 to 250 nm, thus well within the functional limits of the "autonomic gap". Thus epithelial E.C. may be influenced by several types of nervous elements, including CA-fibres.
Adrenergic Fibers↗
A generalized theoretical treatment of the transient-state kinetics of enzymic reaction systems far from equilibrium.
The transient-state kinetics of enzyme systems far from equilibrium have been analyzed by a theoretical treatment of the generalized King-Altman mechanism for enzyme reactions. Conditions are defined under which the kinetics differential equations for this generalized mechanism can be analytically solved, and the structure of the analytical solution is characterized. The practical implications of the theoretical results are discussed with reference to the planning, evaluation, and interpretation of transient-state kinetic experiments performed by stopped-flow techniques.
Enzymes↗