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Cholinergic regulation of biological hydrodynamics
Medical Hypotheses (2000) 54(3), 444–447 © 2000 Harcourt Publishers Ltd DOI: 10.1054/mehy.1999.0873, available online at http://www.idealibrary.com on
Cholinergic regulation of biological hydrodynamics S. Axelsson In association with the Department of Obstetrics and Gynaecology, Swedish University of Agricultural Sciences, Uppsala, Sweden
Summary The structures of biological life are formed in water. Their function depends on changes in the entropy of water. It is regulated by the cholinergic system. The initiating event is the ChE-splitting of water with liberation of free protons. They will draw electrons from the fairly inert dioxygen. The induced oxygen reactivity will give liberation and transfer of electrons and hydrodynamic pH-dependent changes in protein configurations. A multitude of sub-systems will be activated. The sequence of events normally ends with the formation of water, thus preventing uncontrolled radical chain reactions. Cholinergic receptors appear as restricting units of the general disordering entropy tendency. ChE-induced hydrodynamics is propagated to the inner of cells by the water soluble protons and the electrolytes. Especially Ca appear to have a strong influence on the hydrodynamic dipole moment of water. Because water is an integral structure of DNA genetics also will be influenced. Conditions caused by deprivation of oxygen or of reactive oxygen and disorders by hyperactivity and inactivity are briefly discussed. The CNS takes the shape of a large-scale quantum computer with a function far beyond our ability of immediate perception. The atomic nuclear proportions of quantum bits (qubits) will admit the functional one-cell unit of immune memory cells. Cholinergic hydrodynamics appear to substantiate the much discussed chaos theory. © 2000 Harcourt Publishers Ltd
MOVEMENT, WATER AND MEMBRANES Movement is a universal principle. Today both time and space are thought to be moving from the condensed state of a black hole. Gravitational and quantum field forces counteract the dissipative inflation and create aggregations such as galaxies, stars and planets. In micro-cosmos, quarks and leptons form the elements. The orbiting, spinning and vibrations continue in atoms and molecules. This motion of particles can be measured as heat. It was initially of enormous proportions, billions of times hotter than the core of stars with their typical temperatures of 15 million Kelvins. In sharp contrast, biological life is mainly restricted to 0–100° Celsius when water is in liquid phase.
Received 15 February 1999 Accepted 14 April 1999 Correspondence to: Sven Axelsson, 615 32 Valdemensvik, Sweden. Fax: +446 123 10429
444
In temperature regulating species the limit is only a few degrees C. Evidently, water keeps heat-producing motion within limits. Then, hydrophobic–hydrophilic interactions can form the lipid membranes of cells. They will constitute the bedding for functionally complex insertions and anchorings. These structures are the base of the aqueous dynamics of life. CHOLINERGIC PRIORITY A recent study indicated cholinergic lipolytic priority in the regulation of biological hydrodynamics, but also raised some doubts on current concepts of cholinergic function (1). An absolute priority would mean that only the cholinergic system exploits the general entropy tendency of structures. The activation of countless sub-systems should then occur via the produced alterations in aqueous entropism and not by direct activation. Hence, it is only natural that membrane receptors appear as locally stable units in a fluid environment, their versatility obvious by their numbers. In the cholinergic system, receptors
Cholinergic regulation of biological hydrodynamics
most probably stem from ChEs (AChE, BuChE) which have lost their enzymatic activity during evolution, but conserved their common binding structures to acetylcholine (ACh). Consequently, competition will occur with about equal affinities at receptors and ChEs will not per se be involved in receptor channel opening. WATER SPLITTING, DIOXYGEN ACTIVATION AND WATER FORMATION When ChE splits body water, electrons from its hydrogen bonds will stay with the OH-groups in the fairly inert choline (Ch). The protons will then be free in solution; ACh + AChE + H2O → Ch + Ac + AChE + H+. The low buffering capacity of acetate will not prevent the extremely acidic free protons to activate molecular dioxygen by removal of electrons. Thereby, a high energy barrier must be surmounted. It is reflected by the exceptional O2/H2O redox potential of +0.82 V at pH 7. However, free protons do not have their own electrons to prevent close contacts. They will therefore draw electrons from dioxygen at the time scale of nano- to femtoseconds (10–9–10–15 s) which is typical of nuclear motions in solvents (2). The timing and speed of events will be of greatest importance because of the continual need of reactive oxygen for water formation. For example, if a reaction takes place a thousand times faster than another, the probability of its transfer of force (motion) will be increased accordingly. It is the content of water and the basic dioxygen stability that prevent organic material to burn spontaneously. Even in physical combustion, water initially protects from ignition and burning before electrons are removed from dioxygen in an accelerating and uncontrolled way by the exothermic heat (motion) production. In biology, the crucial preventing of excessive radical chain reactions following the removal of one (a) or possibly two (b) electrons can be depicted as; a/ 2H+ + O2 → H2 (stable) + O2 – (reactive superoxide) → 4H+ + O2– → 2H2O, or H+ + 2O2– + RCH3 → H2O + RCH2 O– (radical species), b/ 2H+ + 2O2 → H2O + O22– (reactive peroxide anion), 2H+ + O22– + RCH3 → H2O + RCH2O– (radical species), or 4H+ + 2O22– → 2H2O. Both a/ and b/: RCH2O– + 2e– + 2H+ → RCH3 + H2O. Organic radical species will thus consume free electrons and free protons in their inactivating conversions back to water. Surplus hydrophobic free electrons will move but not solve in water. One part of them will occupy empty atomic and molecular orbitals and thus restore and maintain general molecular stability. Another part of electrons will dissipate to the surroundings from the internal water phase of nerves. Obviously, these often measured currents will reflect only part of cholinergic function. Besides forming dihydrogen oxide (H2O), reactive oxygen will also combine to form other oxides such as nitric oxides and © 2000 Harcourt Publishers Ltd
445
carbon dioxide. Some internal carbon dioxide will be consumed in the proton-buffering bicarbonate cycle. A great deal of hydrogen and carbon dioxide will be formed; HCO3– + H+ → H2 CO3 → H2 CO3 → H2O + CO2. The extraordinarily rapid accommodation of water to alterations in charge distributions will influence protein stereo-conformations on a fluctuating time scale of submicroseconds (10–6–10–10 s). Secondary hydrodynamic activations of for instance enzymes for phosphoryl- and acyl-group transfer will produce more protons: ATP + H2O → ADP + Pi + 2H+, respective AcetylCoA + H2O → Ac + CoA + H+. Only the ChE-action takes place exclusively between cells and organs. This confinement gives ChE the biochemical control of metabolism, later to be propagated into cells and used in the production of high energy metabolites for biological work. PROPAGATION OF HYDRODYNAMICS Gated ChE-hydrodynamics and vectorial membrane properties are conferred to the inner of cells by for instance the water soluble protons and electrolytes (Ca, Na, K). Of prime interest is calcium which is involved in almost all biological activities. It is sometimes regarded as a life and dead signal (3). For example, such an impression is very easy to get from the outcome of treatment of the common bovine paresis syndromes. They proceed with clinical signs of cholinergic dysfunction that varies from tetany to coma and neuromuscular paralysis only. A mortality of ~80% is turned into a ~70% recovery by very heavy Ca-infusions. This is achieved in spite of normal Ca-dissociations and Ca-concentration distributions which largely do not differ from those in physiological conditions such as parturition and oestrus. The stabilization of the chaotically disordered membranes will not depend on providing Ca-channels with more signalling units. More likely, divalent Ca-interactions with water will result in restored dipole moment and order. This important hydrodynamic action of Ca is secondary to a previous ACh-induced change in gating receptor channels. Gated aqueous Ca-, Mg-, Na- and K-channels have also locally specific hydrolytic APTases and will thus deliver protons to the inner of cells. Also nerve signal conduction is a function of ChE-induced hydrodynamic saltatory redistributions of Na and K ions causing hydrophobic electron flow in the water phase of nerve fibres. Since water is an integral structure of DNA, genetics also will be regulated by the aqueous cholinergic entropism. Accordingly, cholinergic activation results in transcription. The immune cells will use the trophic as well as the destructive capacity of ChEs in their respective helper and killer sub-sets, just as plants and primitive organisms have used them in defence and aggression since the beginning of life on earth. Medical Hypotheses (2000) 54(3), 444–447
446
Axelsson
ENERGY TRANSDUCTIONS Metabolic pathways are today known in biochemical details, while their general regulation has been less well understood. By large, cholinergic regulation consists of a change in the physical dimensions of time and space to give duration and proximity for motion transfer between normally inert biomolecules. Solar photons are the main initial source of this motion energy and water is the common starting- and end-product. The decessive role of water is based on the physical fact that all protons of higher biological life are derived from the hydrogen of water. They have no restaints imposed by the strong nuclear forces between protons and neutrons of heavier elements. After ChE-hydrolysis, these protons will not be spatially restrained by orbiting electrons. A great deal of this motion energy is used to build, conserve, restore and stabilize structures. This is a precondition for basic and continued function and constitutes the structural life–death aspect of the cholinergic system. These complicated trophic processes are served by basic cholinergic lipolytic activity. Most important are the energy demanding re-esterification of free fatty acids and the re-cycling of acetyl-groups to choline. ACh will be restored and the so called ‘auto-cannibalism’ of cells will be prevented. Although exothermic, even strong defence reactions will give limited temperature rises due to motion restrictions in the aqueous milleu. An example of physiological lifedetermining function relates to the ChEs in circulation and in erythrocyte and leucocyte membranes. These ChE-enzymes will instantly convert haem-transported dioxygen to reactive oxygen in most locations of an organism. So, anti-oxidants will not produce much water from free radicals under physiological conditions. However, general and local hypoxic or ischaemic conditions by blood flow obstructions will give a deficit of reactive oxygen and thus increase free radicals. ChE-inhibitions will of course have the greatest impact on the availability of reactive oxygen. That is why suffocation is an early sign and cause of death in ChE-inhibitions. Should the enzymes for anaerobic glycolysis be activated, the respite of time will be limited by the low ATPenergy yield of 1/18 compared to the aerobic process. The anoxic protonic mechanism is evident as the severe brain acidosis. DISORDER The very fast and polymorphic ChEs with their varied hydration patterns and anchoring are well suited as normal regulatory units of the tendency to general disorder. They have the double function of activators and inactivators by first splitting water and then induce reactivity of dioxygen for the inactivating formation of water. Acute
Medical Hypotheses (2000) 54(3), 444–447
overactivation results in the well-known swelling of cells with destabilizations and lipolysis of membranes. Even more than water influx, an increased metabolic production of water may explain this enlargement of cells. It may cause membrane blebbing because of the restrictions of disorder imposed by the more stable receptor and filamentous structures (cytoskeleton). Beyond a certain degree of disorder, cell death will occur. The dominating roles of ChEs, especially in the CNS is obvious in acute and chronic ChE-inhibitions. Examples are the almost instant death by nerve gases, in respect to the impressive list of chaotic symptoms in chronic ChE-inhibitions, maybe as in the Gulf War syndrome. Only some of them can be mentioned here; tension, anxiety, restlessness, fatigue, behavioural changes, forgetfulness, insomnia, headache, emotional instability, neurosis, taste aversions, excessive dreaming, spatial memory impairment and nightmares. Besides chemical ChE-inhibition, the psychosomatic effect of war comes to one’s mind, especially since the syndrome is reported from battle places where toxic compounds have hitherto not been suspected (4). TOO MUCH ORDER Irreversible order may be significant in neurodegenerative conditions such as Alzheimers’ disease, the spongiform encephalopathies and in aging. One of initiating events may be random physical breaks in the universal Lchirality, causing formation and aggregation of insoluble heterochiral peptides or whole proteins (5). Single Damino acids will be made harmless by specific D-amino acid oxidases. Therefore, degradation resistant proteins will arise only in the peptide chains of post-translational proteins. Then, more heterochiral proteins will form by lasting cholinergism which gives alignment to the physical templates and thus competitive replication which will increase with the time factor of aging (e.g. amyloidosis). These degradation resistant proteins have lost their stereochemical motility and cannot interact properly with water. The basic physical level(s) is difficult to decide as long as the elementarity of particles remains uncertain (6). Extraterrestrial origin of violation of symmetry (7) indicates an initial cosmic physical break, but contributions from telluric and man made radiation sources can not be excluded. There is of course no evolutionary advantage in a long term lethal process and thus no inheritance of degradation resistant proteins. On the other hand, cholinergic constituents and constitutions are programmed and appear to be self-regulating. TIME AND MIND The ChE-induced chain of reactions occurs on a speed that is far beyond our ability of immediate perception.
© 2000 Harcourt Publishers Ltd
Cholinergic regulation of biological hydrodynamics
The capacity of information in the CNS is related to this velocity and is primarily depending on proton liberations. Electronic currents (EEG) are a consequence and part of the ChE-function and the release of free protons. The random redistributions of electrons in the biological water phase is apparently not adapted to leave the strict binary electricity which is necessary in electronic computers. However, the nuclear spin of protons in for instance carbon and hydrogen nuclei will represent bits of quantum computers (qubits) in molecules (8). The speed of exchange of quantum informations will increase exponentially by qubit numbers (2n) and the whole brain will thus contain and store much more information than the 2-digit electronic computers which do not have the superposition mechanism of qubits and which can be described completely by classical physics. While qubits can be tested experimentally and described by quantum algorithms (9) the biological side will be much more hidden in the complexity of our minds. The CNS will take the shape of a physiological large-scale quantum computer. Its life supporting function is approximately 10 orders of magnitude faster than our ability to realize and react. This ultra-fast world of the CNS governs our minds; the way we think, feel, learn, dream, remember, meditate, enjoy art and music and so on. Moreover, we react and act before we have actually determined to do so. The brain seems to make a decision before our minds become conscious of it. This feature has deeply confounded philosophers for more than two millennia. In the above time aspect it now appears quite normal. When we are aware of something, we have used previous time factor products which will also anticipate what will be thought and done in the nearest future. So, even our free will might be questioned. However, no specificity and consciousness arise from single qubits. So, it must be the correlated patterns of activity in the whole or in parts of the CNS that display a combined awareness in our sensory divisions, which in the first place have also imprinted outside messages for continous quantum exchange storage. The network of supervising cholinergic projections and the parallel processing by countless sub-systems will delay the process to the 10th of a second that we experience on our sensory displays. All processes do not mount to the surface of recognition. Important exceptions are most parts of the autonomous nervous system which is programmed to perform motility, secretory and a lot of other homeostatic functions. Below the level of consciousness are also reflexes from earlier challenges and learning. This will include the important division of
© 2000 Harcourt Publishers Ltd
447
memory cells in the immune system. The dimensions of particles in atoms and thus the number of nuclear qubits in biomolecules will give place for a ‘whole brain’ in one single memory cell. This capacity is based on the natural isolation of the atomic nucleus from the environment. Immune memory cells should conceivably be well suited for studies on biological quantum computing. THE SUBSTANTIATED CHAOS THEORY Cholinergic biodynamics is based on the formation of ordered structures in water and their use in biological work by alternating decreases–increases of disorder in the restrained dipole moment of water. Motion behaviour towards chaos is thus essential for life. Such irregular processes are often described by non-linear mathematics, which predicts that life is a balance on the edge of chaos between self-organization, evolutionary complexity, order and disorder (10). It is therefore no wonder that evolution had to choose mechanisms working in the ordering structures of water. The only exception is the ChE’s double function as activators as well as inhibitors. We are inclined to think negative of chaos, still we have to live on it. ACKNOWLEDGEMENTS The broad-minded support of Dr Kristina Odensvik and Professor Hans Kindahl is highly appreciated.
REFERENCES 1. Axelsson S. Research overview article: Membrane lipolysis and cholinergic priority. Med Hypotheses 1999; 53: 157–165. 2. Fleming G. R. Protein dynamics and photon echoes. Proc Natl Acad Sci USA 1998; 95: 15161–15162. 3. Berridge M. J., Bootman M. D., Lipp P. Calcium – a life and dead signal. Nature; 395: 645–648. 4. Ismail K. et al. Is there a Gulf War syndrome? Lancet 1999; 353: 179–182. 5. Axelsson S. Physical bioenergetics of degradation-resistant proteins in diseases and aging. Med Hypotheses 1988; 51: 47–51. 6. Weinberg S. The first elementary particle. Nature 1997; 386: 213–215. 7. Cronin J. R., Pizzarello S. Enantiomeric excess in meteoritic amino acids. Science 1997; 275: 951–954. 8. Brazzard G., Chuang I., Lloyd, S., Monroe C. Quantum computing. Proc Natl Acad Sci USA 1998; 95: 11032–11033. 9. Chuang I. L., Vandersypen L. M. K., Zhou X., Leung D. W., Lloyd S. Experimental realization of a quantum algorithm. Nature 1998; 393: 143–146. 10. Coffey D. S. Self-organization, complexity and chaos: The new biology for medicine. Nature Med 1998; 4: 882–885.
Medical Hypotheses (2000) 54(3), 444–447
Cholinergic regulation of biological hydrodynamics S. Axelsson In association with the Department of Obstetrics and Gynaecology, Swedish University of Agricultural Sciences, Uppsala, Sweden
Summary The structures of biological life are formed in water. Their function depends on changes in the entropy of water. It is regulated by the cholinergic system. The initiating event is the ChE-splitting of water with liberation of free protons. They will draw electrons from the fairly inert dioxygen. The induced oxygen reactivity will give liberation and transfer of electrons and hydrodynamic pH-dependent changes in protein configurations. A multitude of sub-systems will be activated. The sequence of events normally ends with the formation of water, thus preventing uncontrolled radical chain reactions. Cholinergic receptors appear as restricting units of the general disordering entropy tendency. ChE-induced hydrodynamics is propagated to the inner of cells by the water soluble protons and the electrolytes. Especially Ca appear to have a strong influence on the hydrodynamic dipole moment of water. Because water is an integral structure of DNA genetics also will be influenced. Conditions caused by deprivation of oxygen or of reactive oxygen and disorders by hyperactivity and inactivity are briefly discussed. The CNS takes the shape of a large-scale quantum computer with a function far beyond our ability of immediate perception. The atomic nuclear proportions of quantum bits (qubits) will admit the functional one-cell unit of immune memory cells. Cholinergic hydrodynamics appear to substantiate the much discussed chaos theory. © 2000 Harcourt Publishers Ltd
MOVEMENT, WATER AND MEMBRANES Movement is a universal principle. Today both time and space are thought to be moving from the condensed state of a black hole. Gravitational and quantum field forces counteract the dissipative inflation and create aggregations such as galaxies, stars and planets. In micro-cosmos, quarks and leptons form the elements. The orbiting, spinning and vibrations continue in atoms and molecules. This motion of particles can be measured as heat. It was initially of enormous proportions, billions of times hotter than the core of stars with their typical temperatures of 15 million Kelvins. In sharp contrast, biological life is mainly restricted to 0–100° Celsius when water is in liquid phase.
Received 15 February 1999 Accepted 14 April 1999 Correspondence to: Sven Axelsson, 615 32 Valdemensvik, Sweden. Fax: +446 123 10429
444
In temperature regulating species the limit is only a few degrees C. Evidently, water keeps heat-producing motion within limits. Then, hydrophobic–hydrophilic interactions can form the lipid membranes of cells. They will constitute the bedding for functionally complex insertions and anchorings. These structures are the base of the aqueous dynamics of life. CHOLINERGIC PRIORITY A recent study indicated cholinergic lipolytic priority in the regulation of biological hydrodynamics, but also raised some doubts on current concepts of cholinergic function (1). An absolute priority would mean that only the cholinergic system exploits the general entropy tendency of structures. The activation of countless sub-systems should then occur via the produced alterations in aqueous entropism and not by direct activation. Hence, it is only natural that membrane receptors appear as locally stable units in a fluid environment, their versatility obvious by their numbers. In the cholinergic system, receptors
Cholinergic regulation of biological hydrodynamics
most probably stem from ChEs (AChE, BuChE) which have lost their enzymatic activity during evolution, but conserved their common binding structures to acetylcholine (ACh). Consequently, competition will occur with about equal affinities at receptors and ChEs will not per se be involved in receptor channel opening. WATER SPLITTING, DIOXYGEN ACTIVATION AND WATER FORMATION When ChE splits body water, electrons from its hydrogen bonds will stay with the OH-groups in the fairly inert choline (Ch). The protons will then be free in solution; ACh + AChE + H2O → Ch + Ac + AChE + H+. The low buffering capacity of acetate will not prevent the extremely acidic free protons to activate molecular dioxygen by removal of electrons. Thereby, a high energy barrier must be surmounted. It is reflected by the exceptional O2/H2O redox potential of +0.82 V at pH 7. However, free protons do not have their own electrons to prevent close contacts. They will therefore draw electrons from dioxygen at the time scale of nano- to femtoseconds (10–9–10–15 s) which is typical of nuclear motions in solvents (2). The timing and speed of events will be of greatest importance because of the continual need of reactive oxygen for water formation. For example, if a reaction takes place a thousand times faster than another, the probability of its transfer of force (motion) will be increased accordingly. It is the content of water and the basic dioxygen stability that prevent organic material to burn spontaneously. Even in physical combustion, water initially protects from ignition and burning before electrons are removed from dioxygen in an accelerating and uncontrolled way by the exothermic heat (motion) production. In biology, the crucial preventing of excessive radical chain reactions following the removal of one (a) or possibly two (b) electrons can be depicted as; a/ 2H+ + O2 → H2 (stable) + O2 – (reactive superoxide) → 4H+ + O2– → 2H2O, or H+ + 2O2– + RCH3 → H2O + RCH2 O– (radical species), b/ 2H+ + 2O2 → H2O + O22– (reactive peroxide anion), 2H+ + O22– + RCH3 → H2O + RCH2O– (radical species), or 4H+ + 2O22– → 2H2O. Both a/ and b/: RCH2O– + 2e– + 2H+ → RCH3 + H2O. Organic radical species will thus consume free electrons and free protons in their inactivating conversions back to water. Surplus hydrophobic free electrons will move but not solve in water. One part of them will occupy empty atomic and molecular orbitals and thus restore and maintain general molecular stability. Another part of electrons will dissipate to the surroundings from the internal water phase of nerves. Obviously, these often measured currents will reflect only part of cholinergic function. Besides forming dihydrogen oxide (H2O), reactive oxygen will also combine to form other oxides such as nitric oxides and © 2000 Harcourt Publishers Ltd
445
carbon dioxide. Some internal carbon dioxide will be consumed in the proton-buffering bicarbonate cycle. A great deal of hydrogen and carbon dioxide will be formed; HCO3– + H+ → H2 CO3 → H2 CO3 → H2O + CO2. The extraordinarily rapid accommodation of water to alterations in charge distributions will influence protein stereo-conformations on a fluctuating time scale of submicroseconds (10–6–10–10 s). Secondary hydrodynamic activations of for instance enzymes for phosphoryl- and acyl-group transfer will produce more protons: ATP + H2O → ADP + Pi + 2H+, respective AcetylCoA + H2O → Ac + CoA + H+. Only the ChE-action takes place exclusively between cells and organs. This confinement gives ChE the biochemical control of metabolism, later to be propagated into cells and used in the production of high energy metabolites for biological work. PROPAGATION OF HYDRODYNAMICS Gated ChE-hydrodynamics and vectorial membrane properties are conferred to the inner of cells by for instance the water soluble protons and electrolytes (Ca, Na, K). Of prime interest is calcium which is involved in almost all biological activities. It is sometimes regarded as a life and dead signal (3). For example, such an impression is very easy to get from the outcome of treatment of the common bovine paresis syndromes. They proceed with clinical signs of cholinergic dysfunction that varies from tetany to coma and neuromuscular paralysis only. A mortality of ~80% is turned into a ~70% recovery by very heavy Ca-infusions. This is achieved in spite of normal Ca-dissociations and Ca-concentration distributions which largely do not differ from those in physiological conditions such as parturition and oestrus. The stabilization of the chaotically disordered membranes will not depend on providing Ca-channels with more signalling units. More likely, divalent Ca-interactions with water will result in restored dipole moment and order. This important hydrodynamic action of Ca is secondary to a previous ACh-induced change in gating receptor channels. Gated aqueous Ca-, Mg-, Na- and K-channels have also locally specific hydrolytic APTases and will thus deliver protons to the inner of cells. Also nerve signal conduction is a function of ChE-induced hydrodynamic saltatory redistributions of Na and K ions causing hydrophobic electron flow in the water phase of nerve fibres. Since water is an integral structure of DNA, genetics also will be regulated by the aqueous cholinergic entropism. Accordingly, cholinergic activation results in transcription. The immune cells will use the trophic as well as the destructive capacity of ChEs in their respective helper and killer sub-sets, just as plants and primitive organisms have used them in defence and aggression since the beginning of life on earth. Medical Hypotheses (2000) 54(3), 444–447
446
Axelsson
ENERGY TRANSDUCTIONS Metabolic pathways are today known in biochemical details, while their general regulation has been less well understood. By large, cholinergic regulation consists of a change in the physical dimensions of time and space to give duration and proximity for motion transfer between normally inert biomolecules. Solar photons are the main initial source of this motion energy and water is the common starting- and end-product. The decessive role of water is based on the physical fact that all protons of higher biological life are derived from the hydrogen of water. They have no restaints imposed by the strong nuclear forces between protons and neutrons of heavier elements. After ChE-hydrolysis, these protons will not be spatially restrained by orbiting electrons. A great deal of this motion energy is used to build, conserve, restore and stabilize structures. This is a precondition for basic and continued function and constitutes the structural life–death aspect of the cholinergic system. These complicated trophic processes are served by basic cholinergic lipolytic activity. Most important are the energy demanding re-esterification of free fatty acids and the re-cycling of acetyl-groups to choline. ACh will be restored and the so called ‘auto-cannibalism’ of cells will be prevented. Although exothermic, even strong defence reactions will give limited temperature rises due to motion restrictions in the aqueous milleu. An example of physiological lifedetermining function relates to the ChEs in circulation and in erythrocyte and leucocyte membranes. These ChE-enzymes will instantly convert haem-transported dioxygen to reactive oxygen in most locations of an organism. So, anti-oxidants will not produce much water from free radicals under physiological conditions. However, general and local hypoxic or ischaemic conditions by blood flow obstructions will give a deficit of reactive oxygen and thus increase free radicals. ChE-inhibitions will of course have the greatest impact on the availability of reactive oxygen. That is why suffocation is an early sign and cause of death in ChE-inhibitions. Should the enzymes for anaerobic glycolysis be activated, the respite of time will be limited by the low ATPenergy yield of 1/18 compared to the aerobic process. The anoxic protonic mechanism is evident as the severe brain acidosis. DISORDER The very fast and polymorphic ChEs with their varied hydration patterns and anchoring are well suited as normal regulatory units of the tendency to general disorder. They have the double function of activators and inactivators by first splitting water and then induce reactivity of dioxygen for the inactivating formation of water. Acute
Medical Hypotheses (2000) 54(3), 444–447
overactivation results in the well-known swelling of cells with destabilizations and lipolysis of membranes. Even more than water influx, an increased metabolic production of water may explain this enlargement of cells. It may cause membrane blebbing because of the restrictions of disorder imposed by the more stable receptor and filamentous structures (cytoskeleton). Beyond a certain degree of disorder, cell death will occur. The dominating roles of ChEs, especially in the CNS is obvious in acute and chronic ChE-inhibitions. Examples are the almost instant death by nerve gases, in respect to the impressive list of chaotic symptoms in chronic ChE-inhibitions, maybe as in the Gulf War syndrome. Only some of them can be mentioned here; tension, anxiety, restlessness, fatigue, behavioural changes, forgetfulness, insomnia, headache, emotional instability, neurosis, taste aversions, excessive dreaming, spatial memory impairment and nightmares. Besides chemical ChE-inhibition, the psychosomatic effect of war comes to one’s mind, especially since the syndrome is reported from battle places where toxic compounds have hitherto not been suspected (4). TOO MUCH ORDER Irreversible order may be significant in neurodegenerative conditions such as Alzheimers’ disease, the spongiform encephalopathies and in aging. One of initiating events may be random physical breaks in the universal Lchirality, causing formation and aggregation of insoluble heterochiral peptides or whole proteins (5). Single Damino acids will be made harmless by specific D-amino acid oxidases. Therefore, degradation resistant proteins will arise only in the peptide chains of post-translational proteins. Then, more heterochiral proteins will form by lasting cholinergism which gives alignment to the physical templates and thus competitive replication which will increase with the time factor of aging (e.g. amyloidosis). These degradation resistant proteins have lost their stereochemical motility and cannot interact properly with water. The basic physical level(s) is difficult to decide as long as the elementarity of particles remains uncertain (6). Extraterrestrial origin of violation of symmetry (7) indicates an initial cosmic physical break, but contributions from telluric and man made radiation sources can not be excluded. There is of course no evolutionary advantage in a long term lethal process and thus no inheritance of degradation resistant proteins. On the other hand, cholinergic constituents and constitutions are programmed and appear to be self-regulating. TIME AND MIND The ChE-induced chain of reactions occurs on a speed that is far beyond our ability of immediate perception.
© 2000 Harcourt Publishers Ltd
Cholinergic regulation of biological hydrodynamics
The capacity of information in the CNS is related to this velocity and is primarily depending on proton liberations. Electronic currents (EEG) are a consequence and part of the ChE-function and the release of free protons. The random redistributions of electrons in the biological water phase is apparently not adapted to leave the strict binary electricity which is necessary in electronic computers. However, the nuclear spin of protons in for instance carbon and hydrogen nuclei will represent bits of quantum computers (qubits) in molecules (8). The speed of exchange of quantum informations will increase exponentially by qubit numbers (2n) and the whole brain will thus contain and store much more information than the 2-digit electronic computers which do not have the superposition mechanism of qubits and which can be described completely by classical physics. While qubits can be tested experimentally and described by quantum algorithms (9) the biological side will be much more hidden in the complexity of our minds. The CNS will take the shape of a physiological large-scale quantum computer. Its life supporting function is approximately 10 orders of magnitude faster than our ability to realize and react. This ultra-fast world of the CNS governs our minds; the way we think, feel, learn, dream, remember, meditate, enjoy art and music and so on. Moreover, we react and act before we have actually determined to do so. The brain seems to make a decision before our minds become conscious of it. This feature has deeply confounded philosophers for more than two millennia. In the above time aspect it now appears quite normal. When we are aware of something, we have used previous time factor products which will also anticipate what will be thought and done in the nearest future. So, even our free will might be questioned. However, no specificity and consciousness arise from single qubits. So, it must be the correlated patterns of activity in the whole or in parts of the CNS that display a combined awareness in our sensory divisions, which in the first place have also imprinted outside messages for continous quantum exchange storage. The network of supervising cholinergic projections and the parallel processing by countless sub-systems will delay the process to the 10th of a second that we experience on our sensory displays. All processes do not mount to the surface of recognition. Important exceptions are most parts of the autonomous nervous system which is programmed to perform motility, secretory and a lot of other homeostatic functions. Below the level of consciousness are also reflexes from earlier challenges and learning. This will include the important division of
© 2000 Harcourt Publishers Ltd
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memory cells in the immune system. The dimensions of particles in atoms and thus the number of nuclear qubits in biomolecules will give place for a ‘whole brain’ in one single memory cell. This capacity is based on the natural isolation of the atomic nucleus from the environment. Immune memory cells should conceivably be well suited for studies on biological quantum computing. THE SUBSTANTIATED CHAOS THEORY Cholinergic biodynamics is based on the formation of ordered structures in water and their use in biological work by alternating decreases–increases of disorder in the restrained dipole moment of water. Motion behaviour towards chaos is thus essential for life. Such irregular processes are often described by non-linear mathematics, which predicts that life is a balance on the edge of chaos between self-organization, evolutionary complexity, order and disorder (10). It is therefore no wonder that evolution had to choose mechanisms working in the ordering structures of water. The only exception is the ChE’s double function as activators as well as inhibitors. We are inclined to think negative of chaos, still we have to live on it. ACKNOWLEDGEMENTS The broad-minded support of Dr Kristina Odensvik and Professor Hans Kindahl is highly appreciated.
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