Optimal Diet For Increasing Lifespan

[SAFarmer]

SAFarmer, these are values corrected for cellular activities, in my opinion this is not more than normal.

I did not say my equation is more than normal. I said the true theoretical equation gives an even higher value for ATP production.

What your equation is saying is that that for 1 mole or molecule of glucose you produce 6 moles or molecules CO2 (ratio 1:6). You are correct about these CHO's can't disappear or form out of nowhere. However the formation of 6CO2, 6H2O and 30ATP is not a given certainty for every molecule of glucose you ingest ONLY when it's fully oxidized.

I did say for fully metabolised, didn't I ?

When uncoupling happens for example you produce less ATP, so also less H2O is formed (unless uncoupling proteins also form H2O, but I didn'' dug into this).

This is my point and question. For someone able to give me an example (with balanced equations) and practical explanation of how and what happens during "uncoupling" ito ATP , heat and other products.

So the ATP is variable as is H2O and heat formation.

This I agree and said as much. I just would like to see an example.

Also in practice part of your glucose intake will be converted into lactid acid (in most people). Lactid acid can be converted back to glucose (costs ATP) but also glycogen or protein. Also intermediates from the metabolism of glucose can be converted into amino acids or excreted. Acetyl CoA can be used for the formation of fatty acids (costs ATP). Glucose can be shunted in the pentose phosphate pathway. Probably there are more pathways I can't think of now.

I dont think this was ever in dispute and not the issue of debate.

 

[Such_Saturation]

What exactly is this issue of debate?

 

[visionofstrength]

VOS, With conventional I indeed mean what is currently being taught. Altough the cellular mechanisms may be point of discussion and differ (I didn't day anything about this) the concept of uncoupling stays the same.

...the formation of 6CO2, 6H2O and 30ATP is not a given certainty for every molecule of glucose you ingest ONLY when it's fully oxidized. When uncoupling happens for example you produce less ATP, so also less H2O is formed (unless uncoupling proteins also form H2O, but I didn't dug into this). So the ATP is variable as is H2O and heat formation.

Also in practice part of your glucose intake will be converted into lactid acid (in most people). Lactid acid can be converted back to glucose (costs ATP) but also glycogen or protein. Also intermediates from the metabolism of glucose can be converted into amino acids or excreted. Acetyl CoA can be used for the formation of fatty acids (costs ATP). Glucose can be shunted in the pentose phosphate pathway. Probably there are more pathways I can't think of now.

I see what you mean about there being probably more pathways than you can think of. As I am starting to read Ling's work (in the Peat context) I am seeing (and hopefully beginning to understand) the pathways for Ling-things that Peat suggests, here:

Several decades ago, it was discovered that ATP mediates many processes in the energized cell, but there is still fundamental disagreement on the question of how ATP is synthesized, and how its energy is used to produce movement, to control the movement of water in cells and organs and to regulate the ionic balance of cells and fluids, and even why its absence produces rigor mortis.

When people actually try to examine the question of how the "high energy bond" of ATP can be transformed into usable energy, they sometimes find that it is easier to propose fundamental changes in the laws of physics than to find an explanation within ordinary physics and chemistry. (For example, Physiologie 1986 Jan-Mar;23(1):65-8, "The non-conservation of parity in the domain of elementary particles and a possible mechanism for the delivery of energy from the ATP molecule," Portelli, C.)

...

Despite the present emphasis in "nonlinear dynamics" on random fluctuations and instabilities, the fact is that complex organisms, and finely mixed emulsions, are very stable, and the direction of their development is essentially determinate. Vernadsky described this fact as a law of evolution, that organisms and systems would tend toward the production of a high metabolic rate and large size. This means that evolution tends toward a maximum of energy use, a maximum of adaptive structures. The brain is the dominant organ of adaptation, and the evolutionary tendency toward "cephalization" is an illustration of Vernadsky's law.

The stability of the fine emulsion, or of the evolved organism (a person has greater homeostatic powers than a rat), involves the fact that, within a given range of available energy, the very complex structure has dissipated the energy within itself to a high degree. Every point of the system has come very close to being in equilibrium. It's a situation analogous to that of a road that climbs a mountain with a nearly infinite number of switchbacks—as the number of switchbacks tends toward a maximum, the slope of the road at any point tends toward a minimum.

Mammalian cells are smaller than frog cells; we are like a well homogenized emulsion, compared to animals with lower rates of metabolism. An unstimulated cell is practically in equilibrium with its environment. This is the "high energy resting state." Activity generates structure, but when a cell is inactive, it is stable and doesn't have to expend energy. This is exactly contrary to the doctrine in which a "cell membrane" maintains the cell's organization by a constant expenditure of energy, running "pumps" to maintain differences in the ions and dissolved substances on the opposite sides of the membrane. In that doctrine, each cell, even at rest, is far from equilibrium; life is a struggle, and the cell must spend energy even to stay as it is. Gilbert Ling showed that the concept of membrane pumps to preserve the cell's order is both unnecessary and impossible. In the real organism, energy is spent to grow, to adapt, and to evolve, but not to merely persist.

If we understand Sidney Fox's spontaneously formed microspheres, I think we will get some insights into our own cells. For example, the microspheres have a remarkable uniformity of size, which they preserve even during growth, by dividing instead of simply enlarging. They tend to assemble into orderly chains, without coalescing with each other. They are stable in warm water, but dissolve in cold water. This indicates that the hydrophobic, "fatty" quality of the proteins, causes them to be expelled from the bulk water, forcing them into association with each other. Cold water has greater tolerance for fatty substances. The proteins, however, also contain regions that are water soluble, and when the proteins assemble into droplets, they continue to associate with a certain amount of water. This water is now "dissolved in the protein," in the sense that the properties of the protein are relatively dominant. (Bungenberg de Jong's studies of "complex coacervates" are still the best introduction to this subject.)

The modern practice of biochemists has been to extract soluble substances from cells, and to study them in dilute watery solutions, and then to believe that the things they observe in the test tube are the real properties of cells, of the "dilute solutions enclosed in a lipid membrane." If I hadn't had the experience of talking to dozens of biochemists who believed that no other kind of biochemistry was conceivable, I would find it hard to imagine that something like this could exist in a culture that defines itself as "scientific."

Small particles have a large surface area in proportion to their mass. The balance, within the proteins, between hydrophilic and hydrophobic groups, will determine the proportion of surface area in contact with the bulk solvent water, relative to the mass of the microsphere droplet. More hydrophilic proteins will form smaller droplets, and at a certain point of hydrophilicity, will no longer form droplets. The temperature, by altering the structure of the water, interacts with the hydrophilicity/hydrophobicity of the protein. Structures are generated as complex physical equilibria are achieved.

In our own cells, the microtubules, which are a part of the cell framework involved in cell division and movement, are dissolved at low temperatures, and are reformed when the temperature is raised. Some enzymes have this same temperature sensitivity. Since the water which is "dissolved in the proteins" of the cell is largely dominated by the proteins, its actions on microtubules and enzymes and other proteins will reflect both temperature and the influences of proteins and a variety of dissolved substances. Estrogen, for example, promotes the formation of microtubules, at a given temperature, as if it had made the water "wetter," or warmer.

When cells are stimulated, they adapt, with substance flowing into complexification until an approximate, appropriate equilibrium is reached. Stimulation is a need, and an opportunity, for adaptation and differentiation. If there is a need for adaptation, without the necessary substance and energy, the cell or organism will either deteriorate or withdraw.

Polyunsaturated fats with inappropriate structure interfere with these adaptive flows of energy and substance in all of the known systems of cellular response. These exogenous substances suppress the respiratory energy system, the intercellular communication systems, and the intracellular response systems. Immunodeficiency, autoimmunity, inflammatory diseases, aging, cancer, heart disease, nervous diseases, and hormonal imbalances are produced when these fats interfere with the spontaneous self-regulatory processes of the organism.

When respiration is suppressed, the cell's production of carbon dioxide is suppressed. If we start with the best known example of carbon dioxide's effect on a protein, the Haldane-Bohr effect on hemoglobin, we will have a model for visualizing what happens to organisms in an environment that is poor in carbon dioxide, but rich in vegetable-derived unsaturated fats. Carbon dioxide associates with protein in a variety of ways, but the best understood association is its reaction with an amino group, to form a carbamino group. In the presence of a large amount of carbon dioxide, the hemoglobin molecule changes its shape slightly, along with its electronic balance, in a way that favors the release of oxygen. The opposite happens in the presence of a high concentration of oxygen and a lower concentration of carbon dioxide. Other factors can modify the effects of these gases on hemoglobin's shape, electronic properties, and its binding affinities. Wherever there is lysine or other free amino group (practically every protein and peptide), carbon dioxide can be expected to react with it to some degree, which will depend on other things in the environment. Lysine also reacts with sugars, so there is a competition between CO2 and glucose. In aging and diabetes, many proteins are altered by the inappropriate binding to sugars. There are enzymes which can remove sugars that have altered proteins, but these enzymes are inhibited by the presence of small fragments of starch molecules.

The absence of carbon dioxide bound to a protein is likely to have an effect on the protein's structure and function, but the presence of a relatively large sugar molecule, in a site normally occupied by carbon dioxide, will have drastic effects on the protein, including tending to solublize it, and to cause it to associate with its environment in other abnormal ways. In general, the presence or absence of carbon dioxide involves relatively quick and subtle changes in structure and function, analogous to the phosphorylation of proteins, but possibly competitive with it, while the presence and absence of sugars, as glycated or glycosylated proteins, tends to be relatively permanent, and to require enzymes to restore the original state. Carbon dioxide's regulatory effects have been studied in only a few enzymes and hormones, but there is enough evidence to show that its reactions with proteins and peptides constitute a major regulatory system.

The formation of carbon dioxide itself, from organic materials, has recently been demonstrated to provide the energy for synthesizing ATP. (Arch Microbiol 1998 Aug;170(2):69-77, "Energy conservation in the decarboxylation of dicarboxylic acids by fermenting bacteria," Dimroth P, Schink B.)

Around 1970, someone used a new technique that etched away the surface of a red blood cell, revealing an interior that was obviously highly structured, partitioned into orderly segments, but when I talked to biology professors, they still believed that a red blood cell was "just a bag of hemoglobin, enclosed in a lipid membrane." One of my biochemistry professors, who was smart enough to have opinions of his own, in private sarcastically referred to the "lipid bilayer membrane" as "the fat sandwich theory." But it would be several years before it became socially acceptable to talk about the cell's internal framework. Early in the century, before electron microscopes existed, a biologist had inserted tiny particles of carbon into cells under the microscope, and described their movement as they fell through the cytoplasm as resembling the movement of a pebble falling through a brush pile; it was obvious that the clear cytoplasm was highly structured. The same biologist also rearranged the organelles within the cell, and demonstrated that they spontaneously returned to their normal positions. The cytoplasm can flow like a liquid, but it has some of the properties of a highly organized solid.

When I moved a microelectrode through a cell, using an apparatus that could move it forward or backward in very small increments, I found that the voltage fluctuated with the location in the cell, and that withdrawing or advancing the electrode, each location would show the same voltage as before, when the electrode returned. This meant that, even electrically, the cytoplasm was behaving as a solid, not as a liquid. According to the "membrane theory" of the cell, the liquid part of the cytoplasm has to have the same voltage in all of its parts.

In that doctrine of a cell as "a drop of water containing dissolved molecules enclosed by a membrane," biochemists were required to think that enzyme-catalyzed reactions are governed by random collisions of the substances reacting with the enzymes, and that only a few properties of the solution, such as temperature, pH, and ionic strength, would have any influence on the behavior of the enzyme. Their doctrine seemed tenable to them, at the beginning of the 1970s, only because they had an essentially unscientific attitude that refused to consider the evidence, on the basis that valid evidence couldn't disagree with their position. In the case of hemoglobin, the idea that substances bound to the protein molecule could change its chemical and physical properties was accepted, and by analogy with that, additional "allosteric" (shape-changing) enzymes were beiing studied.

But, because of the commitments made to the "membrane enclosed cytoplasm" theory, the structural proteins were for a long time treated according to the rules established for enzyme chemistry—only local, random interactions were considered to govern their behavior.

In the 1950s, Gilbert Ling introduced a model of the cytoplasm that took account of its observable features. He called it the "Association-Induction" hypothesis. He proposed that substances such as ATP, hormones, and ions participated in cell physiology according to the ways that they associated with proteins and water, and that a powerfully adsorbed molecule, such as ATP, would influence the structural proteins in the cytoplasm as "cardinal adsorbants," altering the proteins' affinity for other adsorbed substances, such as potassium and sodium. The behavior of hemoglobin was a model for the behavior of the cytoplasm and its components. Unfortunately, most biologists didn't even understand the role of adsorbants in hemoglobin's function, so practically no one bothered reading his work. The well-accepted fact of "backbone chemical shift" that results from something as simple as calcium binding to a protein is just another way of talking about the principle of association-induction. The actual chemical structure of the cytoplasmic framework in most types of cell had hardly been studied, and Ling concentrated on studies of the physiology of cells, treating the cytoplasm as an ensemble. Now that many cytoplasmic proteins are being studied in detail, the significance of his cell physiology can be seen more easily.

The "membrane" people like to talk about "ion channels" and "channel proteins," but they are simply describing fragmentary examples of the adsorption-induction process, in which strongly bound substances change the affinity of a protein for small ions and other associated substances. One of the effects of the membrane theory, and of studying enzymes dissolved in water, is that many biochemists got into the habit of thinking of proteins as water-loving materials; otherwise, why would they have to be enclosed by an oily membrane? But, in fact, proteins have a great affinity for fats. Fats are powerful regulatory substances. In excess, the wrong kind of fat associates with the cell framework, and alters that regulatory system, at the same time that it poisons enzymes and other functions. Insoluble proteins tended to be discarded; sometimes they were called "membrane proteins"; when it turned out that the insoluble structural proteins often had "ATPase" functions, this enzyme came to be thought of as the "membrane pump." Even under ordinary assumptions about the way cells use ATP in their energy economy, Gilbert Ling showed that cells don't have the energetic capability of maintaining all of their gradients by "pumping" ions and other dissolved substances. But, the common idea that the phosphate bond in ATP is a very "high energy bond," with 14 kcal of energy, is an unfounded belief; in 1959, for example, Sidney Bernhard showed that a more realistic figure was around 4 kcal. But under relatively water free conditions, the bond forms spontaneously. One of the implications of this fact is that the control of water, the presence or absence of water, and the state of the water, is itself a matter of high-energy interactions. ATP does have a remarkably high energy of adsorption or binding to proteins, and this binding energy allows it to influence the protein's interactions with water. A very thin layer of water between two objects can bind them together very tightly. The structures and movements in cells exist because of very specific interactions between large molecules, especially proteins, and the water which binds them and separates them. Both the water and the proteins are modified by the presence of carbon dioxide.

Two kinds of experiment show that the standard ideas about ATP and pumps have to be reconsidered. When muscles are stretched, they synthesize ATP (Experientia 1971 Jan 15;27(1):45-6, "Stretch induced formation of ATP-32P in glycerinated fibres of insect flight muscle," Ulbrich M, Ruegg JC); this strongly suggests that its synthesis is a physical process, occurring in an environment in which water is inactive, allowing the reaction to be close to equilibrium. (In the heart, stretching has an anabolic effect.) In another experimental setup, the temperature is measured near the surface of a nerve; when the nerve is stimulated, the temperature rises momentarily above the starting temperature, but as the nerve recovers and repolarizes, the temperature falls below the ambient temperature. This "refrigeration," or heat absorption, isn't compatible with the activation of chemically powered "pumps" to restore the initial arrangement of ions, and it suggests something physically closer to the way that heat is emitted and absorbed by a rubber band when it is stretched and then relaxed. When heat production in a myelinated nerve is measured, the membrane theory would require that the heat production, like the electrical potential, should progress in a saltatory manner, jumping from one node to another, but the measurements showed that the heat production moves continuously along the nerve. This supports the idea that the bulk of the cytoplasm is undergoing a progressive phase transition.

Physically, all of these observations (which make no sense in the membrane theory) are compatible with a view of the cytoplasm as a cooperative molecular ensemble that is poised so that its alternative states are close to equilibrium, allowing it to spontaneously revert to its original state following a stimulus that changes its state slightly, or to cause systematic changes in chemical cycles which produce the substances, such as carbon dioxide and ATP, which tend to restore the original state. Nerve conduction, muscle contraction, and secretion are now recognized to involve the factors that cause "allosteric" shifts in molecular structure, association, and affinities. It is the myth of the cell as a "dilute solution organized by a membrane" that prevents the recognition that cell physiology consists primarily of such processes, coordinated into cooperative phase transitions. The recent discovery that cell filaments form responsive systems extending from the cell's surface to the chromosomes makes it possible to see the process of genetic expression as an extension of this organized and unified system.

The standard doctrine about the structure of the membrane is that it is a lipid bilayer, meaning that an outer layer of fat (phospholipid) is arranged with its acidic water-soluble end turned outward toward the watery environment, and its fatty water-repellent tail turned inward, against the fatty tail of another layer of molecules, which has its acidic end turned inward, toward the supposedly watery cytoplasm. In support of this arrangement, an "oil loving" stain is applied to hardened cells (otherwise no membrane can be seen under the electron microscope), and a double line appears near the cell's surface. This is called the "lipid bilayer." However, since the theory says that the fatty parts of the two layers are pressed against each other, there is in the theory a continuous band of fat, separating two layers made up of the acidic heads of the molecules, and the theoretical structure of the "lipid bilayer" has no resemblance to the double line that is created by the stain. The material generally used to produce the image of a bilayer membrane is osmic acid, an oxidant; it wouldn't be expected to stain the layers of acidic heads of fat molecules. This might seem to be an embarrassing inconsistency, but apparently not to most scientists. After the electron microscope began making pictures of cells, it took some time to find the stain that would produce any membrane at all, and then it took about thirty years to learn to produce a "membrane" image that had a thickness that seemed appropriate for the theory. Considering the great effort required to produce a "membrane" image of the right size in the right location, they are willing to overlook the fact that the fat-loving stain hasn't quite found its way to the single band of fat between the acidic layers which their theory describes. Gilbert Ling described the boundary at the cell surface as a phase bouundary, of the sort that exists where two different materials meet, for example at an oil-water interface. When the two substances have different electrical-chemical properties, the forces between the phases move electrons and/or molecules near the surface into what is called an electric double-layer. Since stains have their own electrical and chemical properties, the stain molecules would be affected by the fields that produce an electric double-layer. Osmic acid would be expected to stain certain protein groups, including sulfhydryls and amines, which could be exposed in such an area of strong fields. (Brain tissue that is deprived of oxygen stains diffusely with these "membrane" stains, suggesting that proteins are changing shape sufficiently to expose groups of this sort.) The forces between fat molecules, that allow them to form "hydrophobic bonds," are actually so weak that they should hardly be called "bonds," at least at normal temperatures. Fatty surfaces seem to seek each other out in a watery environment because water molecules bind so powerfully to each other that they tend to force out anything that doesn't bind to them. So, if we even consider the association between fat molecules as a "bond," it is the weakest bond that exists between any biological molecules. When a cell is attached to a surface, it can be torn to bits in trying to move it, without breaking its attachment to the surface. Obviously, it isn't attached to the surface by its "lipid bilayer membrane." The strength of a lipid bilayer would be limited by the extremely weak affinity of fat for fat; if you step on a sticky floor wearing tissue-paper slippers, your foot won't be ripped from your leg. A lipid bilayer has no more strength than the rainbow that forms on a puddle of water when a microscopic film of oil spreads over its surface. And the rainbow on the puddle is something that really exists.

Even though a cell's substance can flow, it has a cohesiveness that can greatly exceed that of ordinary watery solutions. The toughness of a steak isn't affected just by the extracellular connective tissue, as was once believed; the intracellular filamentous materials contribute greatly to its resistance.

Protein filaments can bind cells firmly to the materials that surround them, including other cells. Red blood cells normally float freely in a watery environment, but under some conditions they stack up into a rouleau, roll of coins, formation. The membrane theorists like to explain this pathological association in terms of ionic surface bonds, but experimentalists have pried the cells apart under the microscope, and photographed long extensible, apparently elastic, strands binding them together. The condition appears when the cells' energy is depleted, suggesting that the strands result from an alteration in the cells' internal framework. This kind of process would have practical application in the formation of a clot, producing strength and continuity that would be inconceivable if the red cell were "bags of hemoglobin enclosed in a lipid membrane."

If the cell's cytoplasm can be mechanically continuous with its environment, then the principle of allosterism, the conditionally responsive change of shape and affinities that is recognized in hemoglobin and some enzymes, has the potential for explaining the cell's ability to respond to its environment, and to alter that environment in a controlled way. Filamentous, or other space-encompassing structures in effect are carriers and transmitters of fields of various kinds. A cooperative phase change (cooperativity means that a change which is slow to start will proceed quickly to completion once it gets started, because of interactions of its parts) can occur in a structure which has fluidity, so the signal transmitting function needn't be tied to mechanically fixed filaments. An ensemble of molecules can behave in a coherent manner resembling the behavior of hemoglobin. In fact, hemoglobin is a molecular ensemble which behaves cooperatively, as a functional unit, so there is nothing essentially novel in thinking about larger molecular ensembles making up the cytoplasm.

Ions such as calcium are bound to oppositely charged ions, counter-ions, which are abundant on proteins. As the cell's state changes, calcium (and other) ions can be liberated from the binding proteins, and the momentarily high concentration of ions can serve to transmit an excited and activated state to other molecules, promoting enzyme activity, muscle contraction, nervous transmission, or other cell function. Not long ago, these movements of ions within the cell were explained in terms of membrane pumps and organelle membranes. Now, calcium-binding proteins and "channel proteins" have been identified; the term "channel" derives from the idea that the impermeable membrane had to have pores for the entry and exit of ions and other substances. Supposedly "leakage" through those pores required pumps to compensate by moving substances in the opposite direction. At present, publications on ion channels are more than ten times as frequent as publications on their associated "membrane pumps." Many years ago, it was discovered that large numbers of sulfhydryl groups (a hydrogen bonded to a sulfur atom, which is often in the cysteine group of a protein) appeared during cell division. This represents a rapid and massive change in cell chemistry. The sulfhydryl group is ionizable, but in the late sixties and early seventies when the sulfhydryl shift still seemed important to biologists, there was no support for the idea that these groups could be involved in ion regulation, as part of Gilbert Ling's association-induction model of the cell. However, recently it has been found that a "calcium channel protein" contains a cysteine group that ionizes during the molecule's change of state. (Am J Physiol 1997 Jul;273(1 Pt 1):C230-8, "Possible thiol group involvement in intracellular pH effect on low-conductance Ca(2+)-dependent K+ channels,"Riquelme G, Diaz M, Sepulveda FV.)

Gradually, the idea of allosteric regulatory molecules that are altered by the reversible binding of regulatory substances has gained common acceptance, but the tendency is still to look for these signal receptors at the cell membrane and in association with the control of gene expression. But the cell filaments that make up the cytoskeleton are now known to form continuous systems from the cell surface, through the nuclear membrane, and into the vicinity of the chromosomes. These various filaments have "membrane-like" properties, allowing them to act at, and across, phase boundaries, but also making them sensitive to subtle changes in their environment, such as temperature, ionic balance, and the presence of fatty materials and materials combining various degrees of polarity in their structure; for example, the extremely toxic bacterial endotoxins are lipopolysaccharides, that derive their unique toxicity from the combination of fat and sugar in the same molecule.

For many years, the enzymes of glycolysis were the paradigm for the idea of random interactions between enzymes and their substrates, the materials they catalyze. They were thought to be the most random elements in a randomly organized system. Although it has been over ten years since Sidney Bernhard showed that these enzymes don't wait for their substrates to randomly diffuse into their active sites, this important fact is still generally ignored. (Others, from 1940 to 1998, have reported evidence that the enzymes of glycolysis are "bound to the cell framework.") The ordered behavior Bernhard demonstrated for these "most random" enzymes should be taken as a clue to the nature of other components of the cell.

Rather than having to transmit randomly received signals through random movements into the nucleus, the model of the cell that is implied by the work of Sidney Fox and Gilbert Ling is one in which "receptors" and "effectors" are distibuted throughout the cell substance. Rather than "feedback" of signals along channels of communication to processing centers, the processes of perception and response are distributed throughout a cooperative system, with the possiblity of response governing the process of judgment. There is intelligence in the system at every level, there is no coercion of stupid slave molecules. Fields, forms, associations, and movements all interact in a sensitive and responsive unity. At least they do in health.

In the process of an organism's development, the cell's form precedes its mature chemical functioning. The form depends on the internal framework, and that depends on the cell's contact with a specific kind of extracellular material. The matrix governs the basic pattern of gene expression, acting through the structural elements. In aging and stress, the matrix tends to deteriorate progressively. The matrix, being outside the cell, isn't constantly being renewed as the cell itself is, but it can be enzymically repaired, if the enzymes are not inhibited. Being located between the bloodstream and the metabolizing cells, it is necessarily exposed to all circulating environmental toxins.

There is a functional continuity between the extracellular matrix and the expression of genes. (Weaver and Bissell, 1996; Pienta, et al., 1992.) This has been recognized for several decades by many researchers, but the doctrine of the cell membrane enclosing a watery solution has obstructed progress in this direction.

 

[visionofstrength]

...Probably there are more pathways I can't think of now.

I see what you mean about there being probably more pathways than you can think of. As I am starting to read Ling's work (in the Peat context) I am seeing (and hopefully beginning to understand) the pathways for Ling-things that Peat suggests, here:

And here's one more pathway, that's based on sodium!

The mitochondria of these animals are “uncoupled,” that is, their use of oxygen isn’t directly proportional to the production of ATP. This means that they are producing more carbon dioxide without necessarily producing more ATP, and that even at rest they are using a considerable amount of energy.

One important function of carbon dioxide is to regulate the movement of positively charged alkali metal ions, such as sodium and calcium. When too much calcium enters a cell it activates many enzymes, prevents muscle and nerve cells from relaxing, and ultimately kills the cell. The constant formation of acidic carbon dioxide in the cell allows the cell to remove calcium, along with the small amount of sodium which is constantly entering the cell.

When there is adequate sodium in the extracellular fluid, the continuous inward movement of sodium ions into the resting cell activates an enzyme, sodium-potassium ATPase, causing ATP to break down into ADP and phosphate, which stimulates the consumption of fuel and oxygen to maintain an adequate level of ATP. Increasing the concentration of sodium increases the energy consumption and carbon dioxide production of the cell. The sodium, by increasing carbon dioxide production, protects against the excitatory, toxic effects of the intracellular calcium.

 

[Suikerbuik]

SAFarmer, we can go argue about words like pure theoretical/ theoretical or individual reality. Or if it was point of debate yes or not.

My initial response was "Just keep in mind that these are pure theoretical values." and it seems we agree. At least I didn't disagree with anything you said. I just missed a few things also in relation to some posts I saw being made in the discussion about RQ.

You could take a look at some references here for more info? (possibly slightly outdated or newer info is present somewhere if you look for it). Also Ling's paper could be enlightening maybe?

 

[visionofstrength]

You could take a look at some references here for more info? (possibly slightly outdated or newer info is present somewhere if you look for it). Also Ling's paper could be enlightening maybe?

Thanks! The author Starkov is good enough to allow that the "chemiosmotic theory of energy transduction in mitochondria considers the “classical uncoupling” as a manifestation of “energy-dissipating pathways” which comprise all mechanisms increasing non-productive energy expenditure in mitochondria."

As if to acknowledge, even tacitly, that there might be another (Lingian/Peatian) theory, besides chemiosmosis.

He's got a paper about this here:
http://oxphos.net/staticfile/pubs/Mild% ... ondria.pdf

It's interesting that the paper is dated 1997, and it seems little has changed since. How far have we not come, pursuing chemiosmotic theory?

 

[visionofstrength]

What exactly is this issue of debate?

For me the issue I'm working on is, how does the association-induction hypothesis provide an explanation for excess energy and CO2 generated during uncoupling?

I've been trying to follow up on what you've mentioned in your previous post, that uncoupling energy is produced from phase changes in the structured order of the cell. Here, carbon dioxide is a cardinal adsorbent, adsorbing to proteins, and being exchanged with carboxyls, and activating the enzyme complex, pyruvate dehydrogenase (PDH), which represents the bridge between glycolysis and the Krebs effect.

There also seems to be a similar role for other cardinal adsorbents which, upon gaining or losing electrons, via long-range electronic effects, allow the shift in the preferential adsorption of one ion over another by the ATP generating enzyme, ATPase, as the ATPase enzyme is linked, electronically, to the entire respiratory chain.

There may also be an association-induction explanation for preferring sugar (and insulin) over fatty acids (and ketosis) here:
http://www.andrewkimblog.com/2013/03/wh ... n-and.html

Most of all, I am struck that, where chemiosmosis describes uncoupling as "energy-dissipating pathways", it seems Ling/Peat consider uncoupling to be the very essence of what life is in restful equilibrium.

Of course, I'm using words here that I am just this minute trying to learn, a little like a three year old learning to speak! So please, speak to me!

 

[Such_Saturation]

Maybe it can regulate ATP when there is too much? You only want the very last bit to be bypassed.

 

[Suikerbuik]

I don't know. My guess is that it is likely more than just one reason. Heat is also extremely important for warm blooded animals since all the enzymes are optimised for 37 degrees celsius. UCP's are said to lower reactive oxygen species too.

 

[Such_Saturation]

Yes but when the proton gradient is too strong you can't pump any more protons and the electrons get backed up and spill out (producing superoxides) so that could be a cause and a reason for opening up the floodgates. Also remember there is a well definable optimal ATP to water ratio in the protoplasm.

 

[visionofstrength]

UCP's are said to lower reactive oxygen species too.

Yes but when the proton gradient is too strong you can't pump any more protons and the electrons get backed up and spill out (producing superoxides) so that could be a cause and a reason for opening up the floodgates.

This is something I'm trying to learn about, that mild uncoupling reduces ROS, if it does. Can you help me to understand this? [I've added the bolded]

During the last decade, the possibility that 'mild' uncoupling could be protective against oxidative damage by diminishing ROS (reactive oxygen species) production has attracted much interest. In the present paper, we briefly examine the evidence for this possibility. It is only ROS production from succinate under reverse electron-flow conditions that is sensitive to membrane potential fluctuations, and so only this type of ROS production could be affected; however, the conditions under which succinate-supported ROS production is observed include succinate concentrations that are supraphysiological. Any decrease in membrane potential, even 'mild uncoupling', must necessarily lead to large increases in respiration, i.e. it must be markedly thermogenic. Mitochondria within cells are normally ATP-producing and thus already have a diminished membrane potential, and treatment of cells, organs or animals with small amounts of artificial uncoupler does not seem to have beneficial effects that are explainable via reduced ROS production. Although it has been suggested that members of the uncoupling protein family (UCP1, UCP2 and UCP3) may mediate a mild uncoupling, present evidence does not unequivocally support such an effect, e.g. the absence of the truly uncoupling protein UCP1 is not associated with increased oxidative damage. Thus present evidence does not support mild uncoupling as a physiologically relevant alleviator of oxidative damage.

http://www.ncbi.nlm.nih.gov/pubmed/21936806

there is a well definable optimal ATP to water ratio in the protoplasm.

I'm looking at the idea that uncoupling is a superior way of creating organization and structure from energy, as compared to ATP. Certainly, ATP has its uses, for example, doing work in muscles, but uncoupling may have a higher function, to create an even greater organization and structure in response to "far from equilibrium" conditions, that ATP cannot. Here's Peat's description of how organization and structure are a response to "far from equilibrium" conditions:

Life interposes itself between the "poles" of energy flow, and the flowing energy creates organization and structure, as it is dissipated into heat. Structures store some of the energy, and tend to increase in complexity, taking advantage of the flow of energy to create phase differences with expanded internal surfaces, like a finely mixed emulsion. Like a finely divided emulsion, the more highly energized the organism is, the stabler it is. It adapts to the available energy; energy is used in adaptation; the structures built with the energy are adaptive structures.

This idea of the development of organismic complexity as a response to conditions that are "far from equilibrium" was first clearly stated by V.I. Vernadsky, about 80 years ago...

 

[jyb]

Wa. That quote about comparing life to an emulsion is amazing.

 

[narouz]

Wa. That quote about comparing life to an emulsion is amazing.

Yea...made me think about Peat's comments
concerning art instructing science.
Peat paints with oils (maybe other media too, dunno),
so the emulsion reference gave me a glimpse
of how his art might instruct his science....

 

[visionofstrength]

Wa. That quote about comparing life to an emulsion is amazing.

It is.

Life interposes itself between the "poles"
of energy flow ...like a finely mixed emulsion.
Like a finely divided emulsion ... It adapts
to the available energy; energy is used in adaptation;
the structures built with the energy are adaptive
structures.

I feel like he's channeling the poetry of Blake.

What immortal hand or eye
Dare frame thy fearful symmetry?

Yea...made me think about Peat's comments
concerning art instructing science.

Yes, n, Blake's painting, too.

 

[Amazoniac]

Just wondering:

If we take a look at the Blue Zones hotspots, they almost draw a line that is close to the Equator. Maybe has to do with the warmer climate and mantaining an efficient metabolism with a lesser expense.


http://bloximages.newyork1.vip.townnews ... .image.jpg

 

[Such_Saturation]

Just wondering:

If we take a look at the Blue Zones hotspots, they almost draw a line that is close to the Equator. Maybe has to do with the warmer climate and mantaining an efficient metabolism with a lesser expense.


http://bloximages.newyork1.vip.townnews ... .image.jpg

I don't know but Sardinians have a primarily organ meat and dairy diet in the mountains.

[BBvideo 560,340:g04eeq3l]http://youtu.be/GfzPzPkSX3s[/BBvideo]

 

[visionofstrength]

Just wondering:

If we take a look at the Blue Zones hotspots, they almost draw a line that is close to the Equator. Maybe has to do with the warmer climate and mantaining an efficient metabolism with a lesser expense.


http://bloximages.newyork1.vip.townnews ... .image.jpg

I think the Peatian perspective would be that these isolated populations have imprinted their metabolisms on their progeny for many generations, though the LaMarckian idea of imprinting was dismissed by reductionist molecular biologists, funded by governments whose purpose was to control their populations.

The non-reductionist imprinting of these various peoples would take the form of a kind of collective consciousness or "field" in which the structure and organization typical of these peoples' metabolisms, or perhaps of their uncoupled respiration, have adapted to the energetic practices of the community, and can be passed on from generation to generation even though reductionist genetics plays only a small part in this.

So, for example, if one studied these peoples, one would expect to find that they are all, in one way or another, selecting a diet that minimizes intestinal inflammation and free fatty acids, and that provides essential amino acids without an excess of cysteine, tryptophan, and arginine, while using safe antiinflammatory supplements, perhaps whatever they have available to them locally, to help decrease their susceptibility to stress-induced aerobic glycolysis.

If you read Peat's newsletters, he is really trying, at least by implication, to lay out these strategies that one would expect these "Blue Zone" peoples must all have put in practice over many generations, perhaps each people in its own way.

If you're at all interested in your own health, I would strongly recommend a subscription to Peat's newsletters. It's only 2.33 per issue (in the US, a little more for postage elsewhere). There isn't a better value anywhere.

 

[Such_Saturation]

He still writes them?

 

[visionofstrength]

He still writes them?

Yes, every two months. I didn't know until Milklove told me about it. The ordering information is here:
http://raypeat.com/bookstore/

 

[charlie]

He still writes them?

Yes, every 2 months the newsletter comes out.