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PubMed1980

An hypothesis concerning the molecular structure of the nicotinic acetylcholine receptor.

An hypothesis is presented concerning the molecular structure of the nicotinic acetylcholine receptor at the neuromuscular junction based on the actual amino acid sequence of the N-terminal segment of the alpha-subunit and the Chou and Fasman prediction of secondary structure from the primary sequence. This is mainly in the form of two alpha-helices cross-linked by four ionically bound complementary amino acids (arg/lys to glu). This structure (R) is complementary to a wide range of ACh agonists and to the antagonist beta-erythroidine. If the ionic cross-links are disrupted the two segments can separate by 2-3 A. This new conformation (R1) is now complementary to antagonists of the type of histrionicotoxin. A further separation (approximately 8 A) gives a conformation complementary to antagonist of the type of decamethonium. Experiments to test the hypothesis are suggested.

Acetylcholine↗
PubMed1991

Increased permeability to choline in simian erythrocytes after Plasmodium knowlesi infection.

The permeability of simian erythrocytes to choline was found to be considerably increased after infection by the malaria parasite, Plasmodium knowlesi. Choline entry occurs by a facilitated-diffusion system involving a carrier, which displays temperature-dependence, saturability with choline (Km = 8.5 +/- 0.7 microM) and specificity. This carrier can also be inhibited by a thiol reagent, N-ethylmaleimide, at an inactivation rate which is, in the absence of choline, the same as in normal erythrocytes. Inactivation by N-ethylmaleimide can be accelerated by external choline and prevented by decamethonium, which acts as an inhibitor of choline entry in infected cells (as with dodecyltrimethylammonium). Both ethanolamine and imidazole act as inhibitors or activators of choline entry in infected erythrocytes, depending on the relative concentrations of choline and of the competing compound (i.e. ethanolamine or imidazole). After infection, the maximum velocity reached 2.84 +/- 0.5 nmol/min per 10(10) infected cells, which is more than 10 times the Vmax. of normal erythrocytes. Impairing the biosynthesis of phosphatidylcholine de novo in Plasmodium-infected erythrocytes by various methods (glucose or ATP depletion, high ethanolamine concentrations) did not result in any alteration of choline transport (Km or Vmax.), indicating that the constant triggering and transformation of choline into phosphatidylcholine by the parasite is not directly responsible for the increase in the choline transport rate after infection. This high increase in choline transport activity is more likely related to modifications in choline carriers and/or in their environment after Plasmodium infection.

Animals↗
PubMed1986

Reaction of [3H]meproadifen mustard with membrane-bound Torpedo acetylcholine receptor.

The Torpedo nicotinic acetylcholine receptor (AChR) contains a binding site for aromatic amine noncompetitive antagonists that is distinct from the binding site for agonists and competitive antagonists. To characterize the location and function of this allosteric antagonist site, an alkylating analog of meproadifen has been synthesized, 2-(chloroethylmethylamino)-ethyl-2, 2-diphenylpentanoate HCl (meproadifen mustard). Reaction of [3H]meproadifen mustard with AChR-rich membrane suspensions resulted in specific incorporation of label predominantly into the AChR alpha-subunit with minor incorporation into the beta-subunit. Specific labeling required the presence of high concentration of agonist and was inhibited by reversible noncompetitive antagonists including proadifen, meproadifen, perhydrohistrionicotoxin (HTX), and tetracaine when present at concentrations consistent with the binding affinity of these compounds for the allosteric antagonist site. No specific alkylation of the AChR alpha-subunit was detected in the absence of agonist, or in the presence of the partial agonist phenyltrimethylammonium or the competitive antagonists, d-tubocurarine, gallamine triethiodide, or decamethonium. Reaction with 35 microM meproadifen mustard for 70 min in the presence of carbamylcholine produced no alteration in the concentration of [3H]ACh-binding sites, but decreased by 38 +/- 4% the number of allosteric antagonist sites as measured by [3H]HTX binding. This decrease was not observed when the alkylation reaction was blocked by the presence of HTX. These results lead us to conclude that meproadifen mustard alkylates the allosteric antagonist site in the Torpedo AChR and that part of that site is associated with the AChR alpha-subunit.

Acetylcholine↗
PubMed2004

Evaluation of mechanisms of azinphos-methyl resistance in the codling moth Cydia pomonella (L.).

Resistance of the codling moth Cydia pomonella (L.) to azinphos-methyl is not based on enhanced detoxifying enzymes like oxidation mediated by mixed function oxidases or by glutathione S-transferases. Synergism by S,S,S-tributylphosphoro-trithioate was evident, but the overall activity of general esterases using p-nitrophenyl acetate as the substrate was similar in resistant and susceptible insects. In comparison to acetylcholinesterase (AChE) from susceptible adult codling moth, the enzyme of insects resistant to azinphos-methyl has low affinities (higher K(m) values) to the substrates acetylthiocholine (ATCh) and propionylthiocholine. This difference indicates a possible amino acid alteration at the catalytic or anionic binding sites of the resistant enzyme. Inhibition studies revealed no apparent differences in sensitivity of AChE enzymes from resistant and susceptible moths to organophosphorus compounds (OPs), carbamate insecticides and quaternary ammonium ligands. MEPQ (7-Methylethoxyphosphinyloxy)-1-methylquinolinium) is the most powerful OP inhibitor acting at a nM range, while chlopyrifos oxon, azinphos-methyl oxon and paraoxon are less inhibitory by 22.9, 82.3 and 475 fold, respectively. The codling moth AChE is a typical enzyme that displays substrate inhibition by ATCh, negligible hydrolysis of butyrylthiocholine, very high sensitivity to the bisquaternary ammonium compound BW284c51 and it is not inhibited by the powerful butyrylcholinesterase inhibitor iso-OMPA. Of the three carbamates examined, only carbaryl was inhibitory at the mM range while pirimicarb and aldicarb were inactive. Of the quaternary ammonium ligands (except for the powerful BW284c51), edrophonium and decamethonium displayed appreciable inhibition rates, while d-tubocuraine was practically inactive.

Acetylcholinesterase↗
PubMed1983

Dimethonium, a divalent cation that exerts only a screening effect on the electrostatic potential adjacent to negatively charged phospholipid bilayer membranes.

Calcium and other alkaline earth cations change the electrostatic potential adjacent to negatively charged bilayer membranes both by accumulating in the aqueous diffuse double layer adjacent to the membrane and by adsorbing to the phospholipids. The effects of these cations on the electrostatic potential are described adequately by the Gouy-Chapman-Stern theory. We report the results of experiments with ethane-bis-trimethylammonium, a cation that has been termed "dimethonium" or "ethamethonium" in analogy with hexamethonium (hexane-1,6-bis-trimethylammonium) and decamethonium (decane-1,10-bis-trimethylammonium). We examined the effect of dimethonium on the zeta potential of multilamellar vesicles formed from the negative lipid phosphatidylserine (PS) and from 5:1 phosphatidylcholine/phosphatidylserine mixtures in solutions containing 0.1, 0.01 and 0.001 M sodium, cesium, or tetramethylammonium chloride. We also examined the effect of dimethonium on the conductance of planar PS bilayer membranes and the 31P NMR signal from sonicated PS vesicles formed in 0.1 M NaCl. We found no evidence that dimethonium adsorbs specifically to bilayer membranes. All the results, except for those obtained with vesicles of low charge density formed in a solution with a high salt concentration, are consistent with the predictions of the Gouy-Chapman theory. We conclude that dimethonium, which does not have the pharmacological effects of hexamethonium and decamethonium, is a useful divalent cation for physiologists interested in investigating electrostatic potentials adjacent to biological membranes.

Bis-Trimethylammonium Compounds↗
PubMed1982

Competitive inhibition of 48/80-induced histamine release by benzalkonium chloride and its analogs and the polyamine receptor in mast cells.

Benzalkonium Cl is a family of benzyldimethylalkylammonium compounds which are selective inhibitors of histamine release induced by 48/80 and many other polyamines, but do not inhibit histamine release caused by antigen-antibody reactions, ionophores, enzymes or detergents. In this study, additional histamine-releasing poly- and monoamines found to be antagonized by benzalkonium Cl in rat mast cells were cadaverine, hexamethonium, decamethonium, lysine, dilysine, trilysine, pentalysine, mellitin, pentamidine, spermidine, spermine, morphine, norepinephrine and tyramine. Benzyldimethyltetradecylammonium Cl, one of the safest and most potent members of the benzalkonium Cl family, was found to antagonize 48/80-induced histamine release by a competitive mechanism. Benzyldimethyltetradecylammonium Cl was also found to inhibit 48/80-induced histamine release from mast cells of the hamster in vitro and in the rat, cat and mongoose in vivo. Structure-activity relations studies revealed that: 1) substitution of alkyl, cycloalkyl or other aryl groups for the benzyl group of benzyldimethyltetradecylammonium Cl reduced activity only slightly; 2) demethylation to form the tertiary or secondary amines dramatically reduced activity; 3) optimal length of the alkyl side chain was usually 12 to 14 carbons; and 4) replacement of the nitrogen with phosphorus or sulfur did not significantly alter activity. It appears that the polyamine receptor on mast cells is: 1) widespread in mammals; 2) stimulated by a broad range of polyamines and some monoamines; 3) responsive both in vitro and in vivo; and 4) competitively antagonized by a fairly diverse family of inhibitors possessing a permanent positive charge attached to a substantial but limited hydrophobic moiety.

Animals↗
PubMed1990

Inhibition of nicotine-induced relaxation of the bovine retractor penis muscle by compounds known to have ganglion-blocking properties.

1. The relative potency in blocking the nicotine-induced relaxation of the bovine retractor penis muscle (BRP) was estimated for 12 drugs known to have ganglion-blocking properties. 2. The order of potency of the drugs studied was mecamylamine greater than chlorisondamine greater than pentolinium greater than propantheline greater than (+)-tubocurarine greater than hexamethonium greater than emepronium greater than tetraethylammonium greater than glycopyrrolate greater than decamethonium greater than butylscopolamine greater than scopolamine. 3. The results conform well to those obtained with other pharmacological methods used for the estimation of ganglion-blocking activity. 4. It is concluded that blockade of the nicotinic relaxation of the BRP can be used as an alternative method for quantitative assessment of ganglion-blocking activity. 5. Advantages of this technique are that it discriminates well between antinicotinic and antimuscarinic activity and that it satisfies most or all ethical and economical demands. 6. It is also possible that this method has certain value in predicting whether a drug has enough ganglion-blocking activity to be likely to cause impotence.

Animals↗
PubMed1994

The structure-activity relationship between phenylene-polymethylene bis-ammonium derivatives and their neuromuscular blocking action on mouse phrenic nerve-diaphragm muscle.

The structure-activity relationship of phenylene-polymethylene bis-ammonium (PMBA) derivatives, C6H4[X(CH2)nR]2, on isolated mouse phrenic nerve-diaphragm muscle was investigated to obtain more potent and stable compounds for use as pharmacological tools to clarify the mechanism of succinylcholine (SuCh)-induced neuromuscular blockade. The neuromuscular blocking effect of all the PMBA derivatives was not reversed by neostigmine, a cholinesterase inhibitor. The potency of the neuromuscular blockade was in the order p- > o- > m- with respect to the side-chain substituents. A PMBA composed of X = CH2, n = 5 and R = N+Et3 was 5.9- and 23-fold more potent than SuCh and decamethonium, respectively. The derivatives of R = N+Et3 were observed to be more potent than those of R = N+Me3, N-Me-piperidinio and pyridinio derivatives. Replacement of X = CH2 with O, CHOH and CHOAc decreased the neuromuscular activity while replacement with S, SO and SO2 increased it. Introduction of NO2 into the phenylene ring increased the activity, while the introduction of an alcohol, aldehyde and ketone group decreased it. Removal of a carbonyl or ether group from SuCh decreased its activity, whereas the introduction of these into PMBA failed to increase it. We managed to synthesize unhydrolyzable neuromuscular blocking agents which are more potent than SuCh.

Animals↗
PubMed1981

Alpha-bungarotoxin binding in house fly heads and Torpedo electroplax.

House fly heads contain a site that binds alpha-bungarotoxin with high affinity. It is present at about 23 pmol/g of heads and binds alpha-bungarotoxin (labeled with [3H]pyridoxamine phosphate) reversibly with a Kd of 6 nM. The effects of 48 drugs have been compared on the alpha-bungarotoxin binding sites of house fly and Torpedo. The pharmacology of the house fly sites is similar to that previously reported for neuronal alpha-bungarotoxin binding sites in both vertebrates and invertebrates and is distinguishable from that of the classic nicotinic neuromuscular acetylcholine receptor, as exemplified by that of Torpedo electroplax. Differences between the house fly site and Torpedo include higher affinities of the Torpedo receptor for decamethonium, hexamethonium, carbamylcholine, and acetyl-beta-methylcholine, but lower affinities for nicotine, atropine, and dihydro-beta-erythroidine.

Animals↗
PubMed1986

A comparison between mechanisms of action of different nicotinic blocking agents on rat submandibular ganglia.

The blocking properties of tubocurarine, decamethonium, hexamethonium and trimetaphan on nicotinic agonists applied by repetitive ionophoretic pulses were examined in rat submandibular ganglion cells using a two-microelectrode voltage-clamp technique at 30 degrees C. Hexamethonium, a proposed slowly dissociating, open-channel blocker at concentrations of 2-20 microM did not produce a 'use-dependent' run-down of responses, but its antagonism was clearly dependent on membrane potential. The voltage-dependent reduction of agonist response by hexamethonium was not dependent on the nature of agonist used. Similar results were obtained with acetylcholine (ACh) and carbamylcholine (CCh) ionophoresis. (+)-Tubocurarine (5 microM) and decamethonium (10 microM) produced 'use-dependent' run-down of agonist responses which became more pronounced at higher frequency and as the cell was hyperpolarized, consistent with open-channel blockade. In contrast, trimetaphan (2.5 microM), a receptor antagonist did not cause 'use-dependent' run-down of responses. Hence, the antagonism produced by hexamethonium, unlike tubocurarine and decamethonium, could not be accounted for in terms of open-channel blockade but requires an alternative mechanism, the nature of which is discussed.

Acetylcholine↗
PubMed2006

Quaternary ammonium anticholinesterases have different effects on nicotinic receptors: is there a single binding site?

Copious current research is devoted to finding new modulators of nicotine acetylcholine receptors (nAChRs), in view of their high relevance for nervous system physiology and because alterations in their number and/or function are related to several neurological disorders and neurodegenerative diseases (Pereira et al., 2002). Recently, we have shown that 1,5-bis(4-allyldimethyl ammonium phenyl) pentan-3-one dibromide (BW284c51), a quaternary ammonium cholinesterase inhibitor (QChEI), selectively inhibits nicotinic currents (IACh) by blocking the nAChR channel (Olivera et al., 2005). Interestingly, we found different effects of BW284c51 on nAChRs from those described previously for other QChEIs (Bertrand et al., 1992; Yost and Maestrone, 1994), such as decamethonium and edrophonium. Therefore, this work was aimed at characterizing, comparing, and elucidating the mechanisms underlying the action of different QChEIs on nAChRs.

Acetylcholinesterase↗
PubMed1957

The mechanism of action of murexine on neuromuscular transmission in the frog.

Murexine (urocanoylcholine, [2-beta-imidazol-4(5)-ylacryloyloxyethyl]trimethylammonium chloride hydrochloride) produced a contracture like acetylcholine in the frog rectus and a neuromuscular block in the rat diaphragm which was not relieved by neostigmine but was antagonized by hexamethonium. Using the foot muscle of the frog, electrical recordings showed that murexine produced a neuromuscular block and depolarized the end-plate region. These effects were similar to those seen with suxamethonium, decamethonium and acetylcholine. While murexine had the same depolarizing potency as decamethonium, it was only one-tenth as active as suxamethonium and acetylcholine. It was concluded that murexine could be classified as a "depolarizing type" of neuromuscular blocking agent but was less potent than suxamethonium.

Acetylcholine↗
PubMedDate not supplied

[Acetylcholinesterase. II. Experimental aspects of interaction with reversible effectors under conditions of high ionic strength].

Interaction of usual effectors with acetylcholinesterase (EC 3.1.1.7) from bovine erythrocytes was examined under conditions of high ionic strength (gamma/2 greater than or equal to 0,1). Detailed kinetic investigation of the hydrolysis of acetylcholine by acetylcholinesterase in the presence of modifiers shows that the effects produced by numerous quaternary nitrogen compounds on the enzyme can be explained on the basis of binding of the effectors to the anionic subsite of the active center. The various kinetic behaviors, that are observed, are dependent on the relative values of the deacetylation rate constant ak of the complex acetylated enzyme-modifier and of the rate constant k-2 defined by : (see article) with respect to the value of the deacetylation rate constant K of the acetylated enzyme. If a identical to [1--(k/k-2)]-1, it is shown that interaction of the enzyme with tetraethylammonium, pentamethonium, hexamethonium and gallamine ions is characterized by : a greater than a and k-2 greater than k therefore, these modifiers accelerate deacetylation. On the other hand, inhibition of acetylcholinestase by methylpyridinium, d-tubocurarine, tetra-n-propylammonium, tetra-n-butylammonium, decamethonium and succinylbischoline is consistent with one of the conditions : a less than a and k-2 greater than or equal to k or a greater than a and k-2 less than k and inhibition by tetramethylammonium, phenyltrimethylammonium, 3-hydroxyphenyl-triethylammonium, N-methylacridinium and bis (3-aminopyridinium)-1,10-decane ions agrees with one of the two previous conditions or with : (see article) consequently, the effect of these ligands on the deacetylation step is undetermined. However, the effects of choline chloride, thiazinamium methyl sulfate and thioridazine hydrochloride are not entirely consistent with this mechanism but support the existence of a functional peripheral anionic site which is distinct from the anionic subsite of the active center.

Acetylcholinesterase↗
PubMed1989

Onchidal: a naturally occurring irreversible inhibitor of acetylcholinesterase with a novel mechanism of action.

Onchidal has been identified as the major lipid-soluble component of the defensive secretion of the mollusc Onchidella binneyi, and it has been proposed as the compound responsible for the chemical protection of Onchidella [Bioorg. Chem. 7:125-131 (1978)]. In support of this hypothesis, we now report that onchidal can be found in several different species of Onchidella and that it is toxic to fish. Because onchidal is an acetate ester similar to acetylcholine, its ability to interact with nicotinic acetylcholine receptors and acetylcholinesterase was investigated. Although onchidal did not prevent the binding of 125I-alpha-bungarotoxin to nicotinic acetylcholine receptors, it inhibited acetylcholinesterase in a progressive, apparently irreversible, manner. The apparent affinity of onchidal for the initial reversible binding to acetylcholinesterase (Kd) was approximately 300 microM, and the apparent rate constant for the subsequent irreversible inhibition of enzyme activity (kintact) was approximately 0.1 min-1. Onchidal was a substrate for acetylcholinesterase, and approximately 3250 mol of onchidal were hydrolyzed/mol of enzyme irreversibly inhibited. The calculated kcat for onchidal was 325 min-1. Irreversible inhibition resulted from either onchidal itself or a reactive intermediate in the enzyme-catalyzed hydrolysis of onchidal, rather than from the hydrolysis products of onchidal. Irreversible inhibition of enzyme activity was prevented by coincubation with reversible agents that either sterically block (edrophonium and decamethonium) or allosterically modify (propidium) the acetylcholine binding site. Enzyme activity was not regenerated by incubation with oxime reactivators; therefore, the mechanism of irreversible inhibition does not appear to involve acylation of the active site serine. Because onchidal contains a potentially reactive alpha,beta-unsaturated aldehyde, irreversible inhibition of acetylcholinesterase may result from formation of a novel covalent bond between the toxin and the enzyme. Thus, this novel toxin could potentially be exploited in the design of a new class of anticholinesterase insecticides and in the identification of amino acids that contribute to the binding and hydrolysis of acetylcholine.

Acetylcholinesterase↗
PubMed2003

Pharmacological characterization of recombinant bovine alpha3beta4 neuronal nicotinic receptors stably expressed in HEK 293 cells.

In these studies, [(3)H]epibatidine is used as the radioligand to characterize recombinant bovine alpha3beta4 nicotinic acetylcholine receptors (nAChRs) expressed in HEK 293 cells. Specific binding reaches equilibrium quickly and is saturable with a K(d) value of 0.66 nM. The affinities of the several cholinergic agents were determined, including nicotine (K(i), 0.5 microM), cytisine (K(i), 0.5 microM), carbachol (K(i), 4.1 microM), dihydro-(beta)-erythroidine (K(i), 43.5 microM), d-tubocurarine (K(i), 0.1 microM), 1,1-dimethyl-4-phenylpiperazinium (K(i), 0.5 microM), decamethonium (K(i), 175 microM) and methyllycaconitine (K(i), 0.4 microM). These studies show that the pharmacological characteristics of recombinant bovine alpha3beta4 nAChRs are similar to native bovine alpha3beta4* nAChRs, and indicate that the alpha5 subunit, if present in the native nAChRs, does not affect ligand affinity.

Animals↗
PubMed2002

[3H]Epibatidine binding to bovine adrenal medulla: evidence for alpha3beta4* nicotinic receptors.

In these studies, [3H]epibatidine is used as the radioligand to characterize nicotinic acetylcholine receptors (nAChRs) from bovine adrenal medulla. Specific binding reaches equilibrium within 30 min, and is saturable with a Kd value of 0.5 nM. The affinities of several cholinergic agents were determined, including nicotine (Ki, 0.2 microM), cytisine (Ki, 0.4 microM), carbachol (Ki, 4.7 microM), dihydro-beta-erythrodine (Ki, 33.6 microM), D-tubocurarine (Ki, 0.4 microM), 1,1-dimethyl-4-phenyl-piperazinium (Ki, 0.8 microM), decamethonium (Ki, 234 microM) and methyllycaconitine (Ki, 1.3 microM). These values are similar to reported values for recombinant alpha3beta4 nAChRs in transfected cell lines. These studies demonstrate [3H]epibatidine binding to an easily obtainable adrenal membrane preparation and support the characterization of adrenal nAChRs as alpha3beta4* nAChRs.

Adrenal Medulla↗
PubMed1987

The binding site for alpha-bungarotoxin resides in the sequence 188-201 of the alpha-subunit of acetylcholine receptor: structure, conformation and binding characteristics of peptide [Lys] 188-201.

In order to study where the binding site of cholinergic agents is in the sequence of the alpha-subunit of nicotinic acetylcholine receptor (AChR), we have synthetized 3 peptides with an amino acid sequence corresponding to the following sequences of the alpha-subunit of Torpedo californica AChR: 125-143, 158-167, [Lys] 188-201. For binding studies the peptides were immobilized on Sepharose 4B. Only the peptide [Lys] 188-201 binds 125I-alpha-bungarotoxin (alpha-Bgtx) with Kd of 1.03 microM. The binding of 125I-alpha-Bgtx to the peptide is reduced by 85% after reduction of the S-S bridge present between 192-193 cysteines indicating that an intact disulfide bond is important for toxin binding. The 125I-alpha-Bgtx binding is inhibited by curare, decamethonium, hexamethonium but not by carbamylcholine and Naja naja siamensis alpha-toxin and P15 toxin. All these data provide direct evidence that the sequence 188-201 of the alpha-subunit of AChR binds alpha-Bgtx and that this binding has a pharmacological profile similar to that of nicotinic acetylcholine receptor.

Amino Acid Sequence↗
PubMed1975

Lipid specificity of beta-hydroxybutyrate dehydrogenase activation.

Beef heart mitochondrial beta-hydroxybutyrate dehydrogenase forms a catalytically active complex with lecithin and is inactive in the absence of lecithin. The specificity of the activation process was probed by studying the interaction of the enzyme with phospholipids and other compounds. The compounds were tested for their ability to form active complexes with the enzyme, for the stability of the complex formed, and for the correlation between the activator concentration and the level activation. The phospholipids tested were synthetic lecithins varying in the length (C2 to C18) and degree of unsaturation of the aliphatic chains and in the stereochemistry and type of linkage from the aliphatic chain to the glycerol moiety, synthetic and egg yolk lysolecithins, stearylphosphorylcholine, egg yolk phosphatidylethanolamine, egg yolk phosphatidyl-O-serine, and synthetic cardiolipins. Lecithins, lysolecithins, and stearylphosphoryl-choline form active complexes with the enzyme; the L-alpha-diC4:0 is the smallest lecithin forming an active complex and L-alpha-C12:0 is the smallest lysolecithin. Glycerophosphorycholine, mytistoylcholine, N-trimethyl-n-dodecylamine, decamethonium, sodium dodecyl sulfate, Triton X-100, and Lubrol do not activate the enzyme. A hydrophobic chain followed sequentially by a negative and a positive charge, as in stearylphosphorylcholine, is the minimal structural requirement of an activator. However, the stability of the enzyme-activator complex depends strongly on the aggregation state of the activators, complexes of appreciable stability being formed only with those phospholipids which exist in bilayer membrane-like structures. Thus, lecithins with long aliphatic chains (C9 to C18) form active and stable complexes with the enzyme. The maximal activity and the strength of the lipid-protein interactions depend on the nature of the aliphatic chains of the lipids. Lecithins with saturated and unsaturated fatty acid chains activate the enzyme, but the latter form somewhat more stable complexes. The enzyme-activator interactions in the bilayers can be qualitatively understood in terms of competition between lipid-lipid and lipid-protein interactions: the strength of the interaction between the protein and phosphatidylcholines decreases as the crystalline to amorphous phase transition temperature, which is a measure of the strength of lipid-lipid interactions, increases...

Animals↗