Bioelectrostatics: Review of widespread importance in biochemistry

Kovacic, Peter

doi:10.1016/j.elstat.2007.12.004

Cited by 14 publications

(6 citation statements)

References 34 publications

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“…Electric phenomena, which are key to explaining molecular structure and interactions, demonstrate subtle but essential roles in cellular processes on the nanoscale (9). Local electric fields and charged structures are ubiquitous in the cell (10,11), and hence the electrical nature of a large supramolecular assembly is of critical concern. The highly dense cellular medium nurtures a complex dynamics that involves a multitude of local, albeit globally integrated, processes.…”

Section: Introductionmentioning

confidence: 99%

Single Centrosome Manipulation Reveals Its Electric Charge and Associated Dynamic Structure

Hormeño

Ibarra

Chichón

et al. 2009

Biophysical Journal

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The centrosome is the major microtubule-organizing center in animal cells and consists of a pair of centrioles surrounded by a pericentriolar material. We demonstrate laser manipulation of individual early Drosophila embryo centrosomes in between two microelectrodes to reveal that it is a net negatively charged organelle with a very low isoelectric region (3.1 +/- 0.1). From this single-organelle electrophoresis, we infer an effective charge smaller than or on the order of 10(3) electrons, which corresponds to a surface-charge density significantly smaller than that of microtubules. We show, however, that the charge of the centrosome has a remarkable influence over its own structure. Specifically, we investigate the hydrodynamic behavior of the centrosome by measuring its size by both Stokes law and thermal-fluctuation spectral analysis of force. We find, on the one hand, that the hydrodynamic size of the centrosome is 60% larger than its electron microscopy diameter, and on the other hand, that this physiological expansion is produced by the electric field that drains to the centrosome, a self-effect that modulates its structural behavior via environmental pH. This methodology further proves useful for studying the action of different environmental conditions, such as the presence of Ca(2+), over the thermally induced dynamic structure of the centrosome.

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Section: Introductionmentioning

confidence: 99%

Single Centrosome Manipulation Reveals Its Electric Charge and Associated Dynamic Structure

Hormeño

Ibarra

Chichón

et al. 2009

Biophysical Journal

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“…A review was recently published on the importance of electrical effects in living systems 63. Electroencephalographic (EEG) studies were performed on the effects of mescaline on man 64.…”

Section: Electrical Effectsmentioning

confidence: 99%

“…The proposed quinone metabolite could then be involved in ET. Also, electrostatic fields are believed to participate 63,80. In the case of mescaline, molecular electrostatic potential would be associated with the alkyl ammonium ion that may play a part in receptor binding, in addition to the dipolar carbonyl groups.…”

Section: Cell Signalingmentioning

confidence: 99%

Novel, Unifying Mechanism for Mescaline in The Central Nervous System: Electrochemistry, Catechol Redox Metabolite, Receptor, Cell Signaling and Structure Activity Relationships

Kovacic

Somanathan

2009

Oxidative Medicine and Cellular Longevity

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A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone counterpart. Electron transfer may play a role in electrical effects involving the nervous system in the brain. This approach is in accord with structure activity relationships involving mescaline, abused drugs, catecholamines and etoposide. Inefficient demethylation is in keeping with the various drug properties, such as requirement for high dosage and slow acting.There is a discussion of receptor binding, electrical effects, cell signaling and other modes of action. Mescaline is a nonselective, seretonin receptor agonist. 5-HTP receptors are involved in the stimulus properties. Research addresses the aspect of stereochemical requirements. Receptor binding may involve the proposed quinone metabolite and/or the amino sidechain via protonation. Electroencephalographic studies were performed on the effects of mescaline on men. Spikes are elicited by stimulation of a cortical area. The potentials likely originate in nonsynaptic dendritic membranes. Receptor-mediated signaling pathways were examined which affect mescaline behavior. The hallucinogen belongs to the class of 2AR agonists which regulate pathways in cortical neurons. The research identifies neural and signaling mechanisms responsible for the biological effects. Recently, another hallucinogen, psilocybin, has been included within the unifying mechanistic framework. This mushroom constituent is hydrolyzed to the phenol psilocin, also active, which is subsequently oxidized to an ET o-quinone or iminoquinone.

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“…There is prior mechanistic discussion of electrostatics in connection with various physiologically active N-containing organic cations, such as acetyl choline and zwitterions of GABA and α-amino acids 17. In a critical analysis of the Hofmeister series dealing with various effects of ions, the most active was the ammonium type, and the most active anions were sulfate and phosphate 16. The association with involvement of these ions in cell signaling was pointed out.…”

Section: Electrostaticsmentioning

confidence: 99%

“…The term bioelectrostatics is a label used in the biochemical area in which widespread participation is documented 16. Energetics appears to play a significant role.…”

Section: Introductionmentioning

confidence: 99%

Zolpidem, A Clinical Hypnotic that Affects Electronic Transfer, Alters Synaptic Activity Through Potential Gaba Receptors in the Nervous System Without Significant Free Radical Generation

Kovacic

Somanathan

2009

Oxidative Medicine and Cellular Longevity

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Zolpidem (trade name Ambien) has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET), pharmacodynamics, structure activity relationships (SAR) and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action.The pyridinium cation displays molecular electrostatic potential which may well play a role energetically or as a bridging mechanism. An SAR analysis points to analogy with other physiologically active xenobiotics, namely benzodiazepines and paraquat in the conjugated iminium category. Inactivity of metabolites indicates that the parent is the active form of zolpidem. Absence of reactive oxygen species and oxidative stress is in line with minor side effects. In contrast, generally, the prior literature contains essentially no discussion of these fundamental biochemical relationships. Pharmacodynamics may play an important role. Concerning behavior at the blood-brain barrier, useful insight can be gained from investigations of the related cationic anesthetics that are structurally related to acetyl choline. Evidently, the neutral form of the drug penetrates the neuronal membrane, with the salt form operating at the receptor. The pathways of zolpidem have several clinical implications since the agent affects sedation, electroencephalographic activity, oxidative metabolites and receptors in the central nervous system. The drug acts at the GABA(A) receptor benzodiazepine site, displaying high and intermediate affinities to various receptor regions. Structural features for tight binding were determined. The sedative and anticonvulsant activities are due to its action on the alpha-1-GABA(A) receptors. One of the common adverse responses to zolpidem is hallucinations. Proposed mechanisms comprise changes in the GABA(A) receptor, pharmacodynamic interactions involving serotonin and neuronal-weak photon emission processes entailing redox phenomena. Reports cite cases of abuse with cravings based on anxiolytic and stimulating actions. It is important to recognize that insight concerning processes at the fundamental, molecular level can translate into beneficial results involving both positive and adverse side effects. In order for this to occur, interdisciplinary interaction is necessary. Suggestions are made for future research aimed at testing the various hypotheses.

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Bioelectrostatics: Review of widespread importance in biochemistry

Cited by 14 publications

References 34 publications

Single Centrosome Manipulation Reveals Its Electric Charge and Associated Dynamic Structure

Single Centrosome Manipulation Reveals Its Electric Charge and Associated Dynamic Structure

Novel, Unifying Mechanism for Mescaline in The Central Nervous System: Electrochemistry, Catechol Redox Metabolite, Receptor, Cell Signaling and Structure Activity Relationships

Zolpidem, A Clinical Hypnotic that Affects Electronic Transfer, Alters Synaptic Activity Through Potential Gaba Receptors in the Nervous System Without Significant Free Radical Generation

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