Emergence of homochirality in far-from-equilibrium systems: mechanisms and role in prebiotic chemistry

Since the model proposed by Frank (Frank FC, Biochem Biophys Acta 1953;11:459-463), several alternative models have been developed to explain how an asymmetric non-racemic steady state can be reached by a chirally symmetric chemical reactive system. This paper explains how a stable non-racemic regime can be obtained as a symmetry breaking occurring in a far-from-equilibrium reactive system initiated with an initial imbalance. Departing from the variations around the original Frank's model that are commonly described in the literature, i.e. open-flow systems of direct autocatalytic reactions, we discuss recent developments emphasizing both an active recycling of components and an autocatalytic network of simple reactions. We will present our APED model as the most natural realization of such thermodynamic openness and non-equilibrium, of recycling and of network autocatalysis, each of these in prebiotic conditions. The different experimental and theoretical models in the literature will be classified according to mechanism. The place and role of such self-structured networks responsible for the presence of homochirality in the primitive Earth will be detailed.     

Phenomenon of Life: Between Equilibrium and Non-Linearity

A model of ordering applicable to biological evolution is presented. It is shown that a steady state (more precisely approaching to a steady state) system of irreversible processes, under conditions of disproportionation of entropy, produces a lower-entropy product, that is, ordering. The ordering is defined as restricting of degrees of freedom: freedom of motion, interactions etc. The model differs from previous ones in that it relates the ordering to processes running not far from equilibrium, described in the linear field of non-equilibrium thermodynamics. It is shown that a system, which includes adenosine triphosphate (ATP) to adenosine diphosphate (ADP) conversion meets the demands of the physical model: it provides energy maintaining steady state conditions, and hydrolysis of ATP proceeding with consumption of water can be tightly conjugated with the most important reactions of synthesis of organic polymers (peptides, nucleotide chains etc.), which proceed with release of water. For these and other reasons ATP seems to be a key molecule of prebiotic evolution. It is argued that the elementary chemical reaction proceeding under control of an enzyme is not necessarily far from equilibrium. The experimental evidence supporting this idea, is presented. It is based on isotope data. Carbon isotope distribution in biochemical systems reveals regularity, which is inherent to steady state systems of chemical reactions, proceeding not far from equilibrium. In living organisms this feature appears at the statistical level, as many completely irreversible and non-linear processes occur in organisms. However not-far-from-equilibrium reactions are inherent to biochemical systems as a matter of principle. They are reconcilable with biochemical behavior. Extant organisms are highly evolved entities which, however, show in their basis the same features, as the simplest chemical systems must have had been involved in the origin of life. Some consequences following from the model, which may be significant for understanding the origin of life and the mechanism of biological evolution, are pointed out.     

Non-equilibrium thermodynamics of the selection of biological macromolecules

The Eigen's model for the Darwinian selection of self-reproductive macromolecules is viewed by non-equilibrium thermodynamics of chemical reactions. An excess entropy suitable for the purpose is introduced. It, as the case may be, becomes a Liapunov function to investigate the stability of the selected state characterized by an extremum principle. The selection under the condition for the total concentration of self-reproductive macromolecular species to remain constant in time is discussed on the three cases; the selection described by the simplest Eigen's equation that the effect of mutation is neglected, the selection of quasi-species, and the selective behavior of elementary hypercycle.     

Slugs and snails and opiate tales: opioids and feeding behavior in invertebrates

There is accumulating evidence that opioid systems are involved in the regulation of fundamental behavioral and physiological processes in invertebrates. Feeding is a basic physiological function that is essential for maintaining homeostasis. Results of studies examining the feeding responses of molluscs and arthropods treated with various opiate agonists and antagonists indicate that delta, kappa, mu, and possibly sigma opioid systems differentially and selectively mediate the components of their natural feeding behavior. Moreover, it appears that at an early evolutionary stage the mu and kappa systems have developed to selectively affect the components of feeding behavior associated with the acquisition and ingestion of food. In addition, evidence suggests that neuropeptides that have been proposed as possible endogenous antagonists of opioid-mediated feeding in mammals may also be involved in the control of feeding in invertebrates. This indicates that there may be an interplay of opioid agonists and antagonists in the regulation of feeding and satiation in invertebrates analogous to that proposed for vertebrates. Moreover, these findings indicate that opioid influences on feeding have been conserved through evolution.     

Ionic transport in lipid bilayer membranes.

The current-voltage relationships of model bilayer membranes have been measured in various phospholipid systems, under the influence of both a gradient of potential and an ionic concentration, in order to describe the ion translocation through hydrated transient defects (water channels) across the bilayer formed because of lipid structure fluctuations and induced by temperature. The results have been analyzed in the light of a statistical rate theory for the transport process across a lipid bilayer, recently proposed by Skinner et al. (1993). In order to take into account the observed I-V curves and in particular the deviation from an ohmic behavior observed at high potential values, the original model has been modified, and a new version has been proposed by introducing an additional kinetic process. In this way, a very good agreement with the experimental values has been obtained for all of the systems we have investigated (dimyristoylphosphatidyl ethanolamine bilayers and mixed systems composed by dimyristoylphosphatidyl ethanolamine/dimyristoylphosphatidylcholine mixtures and dimyristoylphosphatidyl ethanolamine/phosphatidic acid dipalmitoyl mixtures). The rate constants governing the reactions at the bilayer interfaces have been evaluated for K+ and Cl- ions, as a function of temperature, from 5 to 35 degrees C and bulk ionic concentrations from 0.02 to 0.2 M. Finally, a comparison between the original model of Skinner and the modified version is presented, and the advantages of this new formulation are briefly discussed.     

Evidence that use of Triton WR1339 underestimates the triacylglycerol entry rate into the plasma of lactating rats owing to continued accumulation of lipid in the mammary gland.

An analysis is presented of the catalytic factors responsible for the rate-enhancement that may be observed when a protein modification reaction is compared with a reaction of the same modifying agent with a model micromolecular compound exhibiting the same reactive group as the protein under study. It is seen that affinity-mediated rate-enhancement of protein modification is realized by the loss of activation entropy. On the assumption that attainment of maximal affinity-mediated rate-enhancement presents with an activation entropy of the protein modification reaction equal to zero, whereas the activation enthalpy of the reaction remains unchanged, it is shown that the value for maximal affinity-mediated rate-enhancement is equal to e-delta s++/R. Accordingly, protein modification reactions may be differentiated into (i) reactions the rate-enhancement of which (relative to the reaction of the same modifying agent with a model compound) is primarily entropy-controlled and (ii) reactions the rate-enhancement of which is primarily enthalpy-controlled. It is seen that modifying agents of low reactivity towards model compounds, but with a high, i.e. highly negative, activation entropy are better suited as prospective affinity-based protein-modifying agents, since the potential affinity-mediated rate-enhancement, and hence the selectivity, of these compounds is necessarily high. Kinetic and thermodynamic constants of the reaction of modifying agents with proteins, and with model compounds, and values of maximal affinity-mediated rate-enhancement, based on published data of the reaction of several modifying agents with model compounds, are presented and discussed.     

Chromatophore heterogeneity explains phenomena seen in Rhodobacter sphaeroides previously attributed to supercomplexes

It is generally considered that metabolic reactions are well described by homogeneous kinetic models in which the reaction phase is statistically uniform. In membranes, especially in photosynthetic systems where the protein complement is high, it has recently been recognized that effects of local heterogeneity might contribute additional factors that perturb the kinetic behavior, and require more extensive treatment. We show in this paper that statistical heterogeneity in vesicular systems can also contribute to quite marked discrepancies from the behavior expected from standard kinetic and thermodynamic models, for reactions involving free diffusion in the aqueous phase. We explain the kinetic and thermodynamic effects observed in studies of photosynthetic electron transfer in cells and chromatophores from Rhodobacter sphaeroides previously attributed to supercomplexes, in terms of a model based on heterogeneity in distribution of electron transfer components among the chromatophore population. We discuss examples of data inconsistent with the supercomplex model, but well explained by the heterogeneity model.     

Coping with the cold: the cold shock response in the Gram-positive soil bacterium Bacillus subtilis

All organisms examined to date, respond to a sudden change in environmental temperature with a specific cascade of adaptation reactions that, in some cases, have been identified and monitored at the molecular level. According to the type of temperature change, this response has been termed heat shock response (HSR) or cold shock response (CSR). During the HSR, a specialized sigma factor has been shown to play a central regulatory role in controlling expression of genes predominantly required to cope with heat-induced alteration of protein conformation. In contrast, after cold shock, nucleic acid structure and proteins interacting with the biological information molecules DNA and RNA appear to play a major cellular role. Currently, no cold-specific sigma factor has been identified. Therefore, unlike the HSR, the CSR appears to be organized as a complex stimulon rather than resembling a regulon. This review has been designed to draw a refined picture of our current understanding of the CSR in Bacillus subtilis. Important processes such as temperature sensing, membrane adaptation, modification of the translation apparatus, as well as nucleoid reorganization and some metabolic aspects, are discussed in brief. Special emphasis is placed on recent findings concerning the nucleic acid binding cold shock proteins, which play a fundamental role, not only during cold shock adaptation but also under optimal growth conditions.     

Effect of microheterogeneity on the sedimentation behavior of self-associating proteins

The effect of microheterogeneity on the sedimentation behavior of self-associating proteins has been examined theoretically with particular reference to rapidly equilibrating tetramerization reactions. Scieral models of microheterogeneity have been considered. Each one exhibits a sedimentation behavior departing substantially from that expected of homogeneous systems. It is anticipated that the results may be helpful for interpreting the sedimentation patterns of self-associating proteins when the patterns cannot be analyzed in terms of the Gilbert theory.     

Pseudomonas cepacia lipase: Esterification reactions in AOT microemulsion systems

Summary The activity of purifiedPseudomonas cepacia lipase has been investigated in esterification reactions of various aliphatic alcohols with natural fatty acids. The reactions were carried out in microemulsions formed in isooctane by bis(2ethylhexyl)sulfosuccinate sodium salt (AOT). The optima pH, T and water content (w_o) for the enzyme activity in this type of microemulsions have been determined. Studies on the effect of various fatty acids and alcohols on the enzyme specificity have shown a preference of this lipase for palmitic and caprylic acid as well as for propanol, while reactions involving cyclic alcohols can not be catalyzed at all. The differences on the behavior of this lipase as compared to other lipases studied in microemulsion systems as well as in other systems are discussed.     

Higher mental functions and the systems analysis of behavior under conditions of uncertainty

Superior psychical functions (skills) are usually formed in great subjective uncertainty conditions. Because of that exact knowledge of information mechanisms of behavior activity under uncertainty conditions is very importent. Some difficulties of traditional notions (classic behavior act model developed by P. K. Anokhin, systems quantization of behavior) are discussed. The model of probabilitive training allows to describe various training uncertainty conditions, and it operates as the Anokhin model in a specific case. The system-shaping factor in this model is an adaptive result. Afferent synthesis, aim for action, acceptor of the action result and the programme of actions have the traditional senses. Besides those it is proposed to use a concept of probability decision to alter the program of action, as well as an idea of memory buffer (results of search reactions). The organizational features of the functional system of behavior under great uncertainty conditions should be taken into account while specifying the informational mechanism responsible for systems quantization of behavior. The above mechanism can be used for explain the discreteness of an action in the program alteration process when the same quantum of behavior is implemented. These ideas are profitable for systems analysis of superior psychical functions, based on the reflex formation under environmental uncertainty conditions.     

Possible mechanisms for forming typological features of behavior of WAG/Rij line rats

Typological behavior reactions of WAG/Rij rats were studied from the standpoint of divergent modulatory integration hypothesis. This rat strain has a genetically determined dominant dysfunction of the benzodiazepine system of the thalamic nuclei. This disorder provokes an epileptiform disease such as absence epilepsy. It was suggested that the dysfunction of this system would result in a modification of the modulatory systems, which support the motivation states of escape and avoidance reactions as well as of the modulatory systems, which form the emotional states. Modifications of these states are the background of typological behavioral features of WAG/Rij rats. It was shown that WAG/Rij have the lower threshold of the development of haloperidol catalepsy, higher levels of fear and depression. On the first day of training in a shuttle box, WAG/Rij rats demonstrated better avoidance performance than Wistar rats. On the second and 28th days, the amnestic effect of the epileptiform disease was observed. The amnestic effect was also observed after passive avoidance conditioning. The results are discussed in terms of the modulatory integratin hypothesis.     

Oscillating reactions in open systems

The probable existence of oscillating chemical reactions has been attracting some interest in recent years for their possible role in explaining certain biological phenomena. Perhaps the simplest model of oscillating reactions is that of Lotka (1910), which consists of a chain of autocatalytic reactions. Two “reactor systems” in which such a chain of reactions could take place are considered in this work and are called homogeneous and compartmental models, respectively. The differential equations governing the temporal behavior of the reacting species are solved on an analog computer, and the conditions under which sustained oscillations occur are obtained and discussed. Comparisons of the solution obtained in the two models are discussed.     

The role of the anion in the reaction of reducing sugars with ammonium salts

Reactions of reducing sugars with ammonia and its compounds are important commercially, particularly in the preparation of flavors and caramel colors. However, such reactions generally produce a complex series of products ranging from simple molecules to complex polymeric materials, particularly since commercial systems generally involve mixtures of sugars as opposed to single sugars. This complexity has made understanding the mechanisms of such reactions difficult. Therefore, investigatory work has generally been focused on model systems. Herein we report one such study with model systems: the effects of the nature of the anion of the reactions of reducing sugars with ammonium salts. D-Glucose was reacted in aqueous solution with each of the following ammonium salts: acetate, bicarbonate, carbonate, chloride, citrate, formate, monohydrogenphosphate (DAP), sulfate, and sulfite. These reactions were carried out in a Parr bomb at 93 degrees C for 2.5 h. The initial pH of the reaction mixtures was adjusted to pH 8.0 at 25 degrees C. The resulting mixtures were analyzed by LC-MS, and the results were analyzed by comparing the product yields and distributions with those obtained with DAP. The major reaction product of interest was 2,6-deoxyfructosazine, as it had been shown to be a marker for the polymeric material formed from such reactions. It was found that ammonium salts of weak acids were much more effective in effecting the desired reactions than were those of strong acids; however, none was as effective as DAP.     

On the validity of Shannon-information calculations for molecular biological sequences

The usefulness of information-theoretic measures of the Shannon-Weaver type, when applied to molecular biological systems such as DNA or protein sequences, has been critically evaluated. It is shown that entropy can be re-expressed in dimensionless terms, thereby making it commensurate with information. Further, we have identified processes in which entropy S and information H change in opposite directions. These processes of opposing signs for delta S and delta H demonstrate that while the Second Law of Thermodynamics mandates that entropy always increases, it places no such restrictions on changes in information. Additionally, we have developed equations permitting information calculations, incorporating conditional occurrence probabilities, on DNA and protein sequences. When the results of such calculations are compared for sequences of various general types, there are no informational content patterns. We conclude that information-theoretic calculations of the present level of sophistication do not provide any useful insights into molecular biological sequences.     

NE-100, a novel sigma receptor ligand: In vivo tests

It has been suggested that sigma receptor antagonists may be useful as antipsychotic drugs. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) is a novel compound with high affinity for the sigma receptor (IC50 = 4.16 nM), but low affinity (IC50 > 1000 nM) for D1, D2, 5-HT1A, 5-HT2 and phencyclidine (PCP) receptors. The head-weaving behavior induced by either (+)SKF10047 or PCP was dose-dependently antagonized by NE-100 with oral ED50 at 0.27 and 0.12 mg/kg, respectively. NE-100 did not affect dopamine agonists-induced stereotyped behavior and/or hyperactivity. NE-100 failed to induce catalepsy in rats. These findings indicate that NE-100 may have antipsychotic activity without the liability of motor side effects typical of neuroleptics.