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<h1>Membranes, plasma membranes, and surfaces</h1>
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<p class="nav"><span class="nav-left">Listed under <a href="/ray-peat.html">Ray Peat</a>.</span><span class="nav-right"><a href="/theme.html">Theme</a></span></p>
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<p>From the <a href="https://raypeat.com/articles/articles/membranes.shtml" target="_blank">original article</a> in 2009. Author: <a href="https://raypeat.com/" target="_blank">Ray Peat</a>.</p>
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<p>The
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"essential fatty acids":</p>
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<p>Suppress
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metabolism and promote obesity; are immunosuppressive; cause inflammation
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and shock; are required for alcoholic liver cirrhosis; sensitize to
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radiation damage; accelerate formation of aging pigment, cataracts,
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retinal degeneration; promote free radical damage and excitoxicity;
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cause cancer and accelerate its growth; are toxic to the heart muscle
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and promote atherosclerosis; can cause brain edema, diabetes, excessive
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vascular permeability, precocious puberty, progesterone deficiency....</p>
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<p>Twice,
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editors have printed my articles on unsaturated fats, with adjoining
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"rebuttals," but I was disappointed that all of my points
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were ignored, as if you could rebut an argument by just saying that
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you emphatically disagree with it. I think it is evident that those
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people don't know what would be involved in refuting an argument. They
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are annoyed that I have bothered them with some evidence, but not sufficiently
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annoyed to cause them to try to marshal some evidence against my arguments.</p>
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<p>Marketing
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and medical claims are intertwined with a view of life that permeates
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our culture. I am aware that my criticism of the doctrine of the essentiality
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of linoleic acid threatens the large profits of many people, and threatens
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the prestige of the most popular "theory of cell structure,"
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but I think it is important to point out that nutritional and medical
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advice depend on the truth of the theory of cell structure and function
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which supports that advice, and so it is reasonable to see how sound
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that theory is.</p>
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<p>As
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I understand it, the doctrine of the "essential fatty acids"
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goes this way: </p>
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<p>1.
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They are essential because they are required for making cell membranes
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and prostaglandins. </p>
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<p>2.
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Rats deprived of the unsaturated fatty acids develop a skin disease,
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and "lose water" through the skin. </p>
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<p>3.
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Human skin diseases (etc.) can be cured with polyunsaturated fats.
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</p>
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<p>In
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fact, rats may get a skin disease when fed a fat-free diet, but the
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observation that vitamin B6 cures it should have laid to rest the issue
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of the dietary essentiality of the polyunsaturated oils more than 50
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years ago. Scientifically, it did, but forces greater than science have
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revivified the monster. Experiments that confirm the disproof are done
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periodically--animals living generation after generation without unsaturated
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oils in their diet or any evidence of harm, human cells growing in culture-dishes
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without polyunsaturated fats, for example--without noticeable effect
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on the doctrine, which is perpetuated in many effective, nonscientific
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ways--textbooks, advertisements, college courses, for example.</p>
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<p>Now,
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instead of demonstrating harm from a dietary lack of the "essential"
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fats, the presence of the Mead acid or omega-9 fatty acids is taken
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as evidence of a deficiency. Our cells (and animal cells) produce these
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unsaturated fats when their special desaturase enzymes are not suppressed
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by the presence of exogenous linoleic or linolenic acids. Normally,
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the inactivation of an enzyme system and the suppression of a natural
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biological process might be taken as evidence of toxicity of the vegetable
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oils, but here, the occurrence of the natural process is taken as evidence
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of a deficiency. To me, this seems very much like the "disease"
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of having tonsils, an appendix, or a foreskin--if it is there, you have
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a problem, according to the aggressive surgical mentality. But what
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is the "problem" in the case of the natural Mead or omega-9
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acids? (I think the "problem" is simply that they allow us
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to live at a higher energy level, with greater resistance to stress,
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better immunity, and quicker healing.)</p>
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<p>There
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have been arguments based on "membranes" and on prostaglandins.
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The absence of "good" prostaglandins would seem to be an obvious
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problem, except that the "good" prostaglandins always turn
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out to have some seriously bad effects when examined in other contexts.
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Animals that lack dietary unsaturated fats appear to escape most of
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the problems that are associated with prostaglandins, and I think this
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means that many of the toxic effects of the unsaturated vegetable oils
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result from the quantity and type of "eicosanoid"/lipoxygenase
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products made from them.</p>
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<p>One
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type of membrane argument had to do with the fragility of red blood
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cells, reasoning, apparently, that the cells are "held together"
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by a lipid bilayer membrane. (Just what is the tensile strength of a
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lipid bilayer? Why do fatty acids or saponins weaken blood cells, instead
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of reinforcing them? If the "tensile strength" of a lipid
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layer exists, and is positive rather than negative, it is negligible
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in relation to the tensile strength of the cytoplasm.) Another type
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of :"membrane" argument was that the mitochondria are abnormal
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when animals don't get the essential fatty acids in their diet, because
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the mitochondria are supposed to be essentially membranous structures
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containing the essential fatty acids. (Actually, the deficient mitochondria
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produce more ATP than do mitochondria from animals fed the vegetable
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oils.) Another argument is that "membrane fluidity" is a good
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thing, and that unsaturated essential fatty acids make the membranes
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more fluid and thus better--by analogy with their lower bulk-phase melting
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temperature. (But the measure of fluidity is a very limited thing on
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the molecular level, and this fluidity may be associated with decreased
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cellular function, instead of the postulated increase.)</p>
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<p>The
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most addled sort of argument about "membranes" is that animals
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on the diet lacking polyunsaturated oils have skin that is unable to
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retain water because of "defective cell membranes." The skin's
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actual barrier function is the result of mulptile layers of keratinized
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("cornified," horny) cells, which have become specialized
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by their massive production of the protein keratin--very much as red
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blood cells become specialized by producing the protein, hemoglobin.
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Since these cells lose most of their water as they become horny, the
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issue of whether they still have a "plasma membrane" seems
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to have little interest to researchers; the same can be said regarding
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the cells of hair and nails. After the epidermal cells have become keratinized
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and inert, the sebaceous glands in the skin secrete oils, which are
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absorbed by the dense, proteinaceous cells, causing increased resistance
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to water absorption. The ideas of a plasma membrane on the cell, and
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of the water-barrier function of the skin, are two distinct things,
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that have been blurred together in a thoughtless way. It has been suggested
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that vitamin B6 cures the characteristic skin disorder of a vitamin
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B6 deficiency by altering fat metabolism, but the vitamin is involved
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in cell division and many other processes that affect the skin.</p>
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<p>Given
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the fact that the "essential" oils aren't essential for the
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growth of cells, they can't be essential for making plasma membranes
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(if cells must have plasma membranes), or mitochondrial membranes, or
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any kind of membrane, but as long as there is the idea that fats mainly
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have the function of building membranes, someone is going to argue that
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membranes containing vegetable oils are more fluid, or more youthful,
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or more sensitive, or better in some way than those containing Mead
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acids, palmitic acid, oleic acid, stearic acid, etc.</p>
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<p>For
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over a century, people have suggested that cells are enclosed in an
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oily membrane, because there are higher or lower concentrations of many
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water-soluble substances inside cells, than in the blood, lymph, and
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other extracellular fluids, and the idea of a membrane was invoked (W.
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Pfeffer, 1877; E. Overton, 1895, 1902) to explain how that difference
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can persist. (By 1904, the idea of a membrane largely made of lecithin
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was made ludicrous by A. Nathansohn's observation that water-soaked
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lecithin loses its oily property, and becomes very hydrophilic; the
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membrane was supposed to exclude water-soluble molecules while admitting
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oil-soluble molecules.)</p>
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<p>Inside
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the cell membrane, the cell substance was seen as a watery solution.
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Biochemistry, as a profession, was strongly based on the assumption
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that, when a tissue is ground up in water, the dilute extract closely
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reflects the conditions that existed in the living cell. Around 1970,
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when I tried to talk to biochemists about ways to study the chemistry
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of cells that would more closely reflected the living state, a typical
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response was that the idea was ridiculous, because it questioned the
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existence of biochemistry itself as a meaningful science.. But since
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then, there has been a progressive recognition that organization is
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more important in the life of a cell than had been recognized by traditional
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biochemistry. Still, many biochemists thoughtlessly identify the chemistry
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of the living cell with their study of the water-soluble enzymes, and
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relegate the insoluble residue of the cell to "membrane-associated
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proteins" or, less traditionally, to "structural proteins."
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It has been several decades since the structural/contractile protein
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of muscle was found to be an enzyme, an ATPase, but the idea that the
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cell itself is a sort of watery solution, in which the water-soluble
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enzymes float, randomly mingling with dissolved salts, sugars, etc.,
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persists, and makes the idea of a semipermeable membrane seem necessary,
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to separate a "watery internal phase" from the watery external
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phase. Physical chemists have no trouble with the fact that a moist
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protein can absorb oil as well as water, and the concept that even water-soluble
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enzymes have oil-loving interiors is well established. If that physical-chemical
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information had existed in Overton's time, there would have been no
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urge to postulate an oily membrane around cells, to allow substances
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to pass into them, in proportion to their solubility in oil.</p>
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<p>Because
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biochemists like to study their enzymes in watery test-tube solutions,
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they find it easy to think of the cell-substance as a watery solution.
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With that belief, it is natural that they prefer to think of the primeval
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ocean as where life originated. Their definitions of chemical reactions
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and equilibria in the water-phase (and by extension in cells) ignore
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the alternative reactions and equilibria that would occur in an environment
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in which ordinary water was not the dominant medium. By this failure
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to consider the alternatives, they have created some problems that are
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hard to explain. For example, the polymerization of amino acids into
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protein is energetically expensive in water, but it is spontaneous in
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a relatively dry environment, and this spontaneous reaction creates
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non-random structures with the capacity for building larger structures,
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with stainable bilayer "membranes," and with catalytic action.
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(Sidney Fox, 1965, 1973.) Similarly, the problem of ATP synthesis essentially
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disappears when it is considered in an environment that controls water.
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The scientific basis for the origin of life in a "primeval soup"
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never really existed, and more people are now expressing their scepticism.
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However, biochemists have their commitments:</p>
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<p>"In
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the course of biological evolution, one of the first developments must
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have been an oily membrane that enclosed the water-soluble molecules
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of the primitive cell, segregating them and allowing them to accumulate
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to relatively high concentrations. The molecules and ions contained
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within a living organism differ in kind and in concentration from those
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in the organism's surrounding." (Principles of Biochemistry, supposedly
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by Lehninger, Nelson, and Cox, though Lehninger is dead and I think
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his name is attached to it to exploit his fame.# Worth Publishers, 1993.)</p>
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<p>Hair
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is composed of thoroughly dead cells, but if it is washed until it contains
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no sodium or potassium, and then dipped in serum, or a solution of sodium
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and potassium, it takes up much more potassium than sodium, in the way
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a living cell does, concentrating potassium "against the gradient."
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That is the sort of behavior that led to the postulation of a plasma
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membrane, to maintain the organization that was created by expending
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energy. "Membrane pumps" use energy, supposedly, to establish
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the concentration difference, and the barrier membrane keeps the solutes
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from diffusing away. The lipid bilayer membrane was an early guess,
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and the pumps were added later, as needed. Gilbert Ling reviewed the
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published studies on the various "membrane pumps," and found
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that the energy needed to operate them was 15 times greater than all
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the energy the cell could possibly produce.</p>
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<p>Water
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softeners contain an ion-exchange resin, that uses the same principle
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hair does to concentrate ions, which is simply a selectivity based on
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the acidity of the resin, and the size of the ion. The resin binds calcium
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more strongly than it binds sodium, and so the water gives up its calcium
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in exchange for sodium.* Gilbert Ling devised many experiments that
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demonstrated the passivity of ion-accumulation by living cells.</p>
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<p>Usually,
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cells are surrounded by and imbedded in materials that they have secreted,
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and their surfaces are often covered with materials that, while remaining
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anchored to the cell, have a considerable affinity for water. Physically,
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many of the molecules attached to cells are "surfactants,"
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making the cell wettable, though it isn't customary to describe them
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as such. The glycoproteins that give cells their characteristic immunological
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properties are among these materials. At a certain point, there is a
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transition between the "outside" of the cell, which is relatively
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passive and water-friendly, and the cell itself, in which water is subordinated
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to the special conditions of the cell. (The postulated lipid bilayer
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membrane, in contrast, has two phase discontinuities, one where it meets
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the cytoplasm, another where it meets the outside world.) At this phase
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boundary, between two different substances, it is normal to find an
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electrical potential difference. When two electrically different substances
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are in contact, it isn't surprising to find an electrical double-layer
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at the surface. This is a passive process, which doesn't take any energy
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to maintain, but it can account for specific arrangements of molecules
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in the region of the phase boundary, since they are exposed to the electrical
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force of the electrical double-layer. That is to say that in a completely
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inert and homogeneous substance, a "surface structure" will
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be generated, as a result of the electrical difference between that
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substance and the adjoining substance. (This surface structure, if it
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is to be described as a membrane, must be called a "wet membrane,"
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while the lipid bilayer would be a "dry membrane," since exclusion
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of water is its reason for existing.) Too many biologists still talk
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about "electrogenic membrane pumps," indicating that they
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haven't assimilated the results of Gilbert Ling's research.</p>
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<p>To
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say it another way, there are several kinds of physical process that
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will govern the behavior of fats, and fats of different types will interact
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in different ways with their environments. They interact complexly with
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their environment, serving in many cases as regulatory signal-substances.
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To describe their role as "membranes" is worse than useless.</p>
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<p>Cells
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can be treated with solvents to remove practically all fats, yet the
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cells can still show their characteristic membranes: Plasma membrane,
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mitochondrial membranes, even the myelin figures. The proteins that
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remain after the extraction of the fats appear to govern the structure
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of the cell.</p>
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<p>A
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small drop of water can float for a moment on the surface of water;
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this is explained in terms of the organization of the water molecules
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near the surface. No membrane is needed to explain this reluctance to
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coalesce, even though water has a very high affinity for water.</p>
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<p>People
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believed in the "lipid bilayer membrane" for decades before
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the electron microscope was able to produce an image that could be said
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to correspond to that theoretical structure. Osmic acid, which is believed
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to stain fats, does produce a double layer at the surface of cells.
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However, the arrangement of fat molecules in the lipid bilayer is such
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that the fatty tails of the two layers are touching each other, while
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their acidic heads are pointed away from each other. A lipid bilayer,
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in other words, contains a single zone of fat, bounded by two layers
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of acid. The "fat-staining" property of osmic acid, then,
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argues against the lipid bilayer structure.</p>
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<p>Osmic
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acid is very easily reduced electrically, forming a black product. Proteins
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with their sulfur molecules in a reduced state, for example, would cause
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an osmium compound to be deposited, and the appearance of two layers
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of osmium at the cell's phase boundary would be compatible with the
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idea of an electrical double-layer, induced in proteins.</p>
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<p>Electrically
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charged proteins, which are able to interact with glutathione to increase
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or decrease their degree of reduction/electrical charge, distributed
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throughout the cytoplasm, would explain another feature of osmic acid
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staining, which is incompatible with the "fat-staining" concept.
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Asphyxia increases the stainability of cells with osmic acid, and this
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change seems to represent the availability of electrons, rather than
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the distribution of fats, since the change can appear within 3 minutes.
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(C. Peracchia and J. D. Robertson, <strong>"Increase in osmiophilia
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of axonal membranes of crayfish as a result of electrical stimulation,
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asphyxia, or treatment with reducing agents,"</strong> J. Cell Biol.
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51, 223, 1971; N. N. Bogolepov, Ultrastructure of the Brain in Hypoxia,
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Mir, Moscow, 1983) The amino groups of proteins might also be stained
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by osmic acid, though asphyxia would more directly affect the disulfide
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groups. The increased staining with silver in asphyxia similarly suggests
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an increase in sulfhydryls.</p>
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<p>Freezing
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cells, and then fracturing them and coating the fragments with metal
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or carbon is often used to "demonstrate the lipid bilayer,"
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so it is interesting that the <strong>osmium compound that "reveals"
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the lipid bilayer for the electron microscope destroys the apparent
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membrane in the freezing technique.</strong> (R. James and D. Branton, "The
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correlation between the saturation of membrane fatty acids and the presence
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of membrane fracture faces after osmium fixation," Biochim. Biophys.
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Acta 233, 504-512, 1971; M. V. Nermut and B. J. Ward, <strong>"Effect
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of fixatives on fracture plane in red blood cells," J. Microsc.
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102, 29-39, 1974.)</strong></p>
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<p>So,
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when someone says "we need the essential fatty acids to make cell
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membranes," my response is likely to be "no, we don't, and
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life probably originated on hot lava and has never needed lipid membranes."</p>
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<p>On
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the third argument, that vegetable oils can be used therapeutically,
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I am likely to say yes, they do have some drug-like actions, for example,
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linseed oil has been used as a purgative, but as with any drug you should
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make sure that the side effects are going to be acceptable to you. Currently,
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it is popular to recommend polyunsaturated oils to treat eczema and
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psoriasis. These oils are immunosuppressive, so it is reasonable to
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think that there might be some pleasant consequences if a certain immunological
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process is suppressed, but they are also intimately involved with inflammation,
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sensitivity to ultraviolet light, and many other undesirable things.
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The traditional use of coal tar and ultraviolet light was helpful in
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suppressing eczema and psoriasis, but its tendency to cause cancer has
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led many people to forego its benefits to protect their health.</p>
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<p>If
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you want to use a polyunsaturated oil as a drug, it is worthwhile to
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remember that the "essential fatty acids" suppress metabolism
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and promote obesity; are immunosuppressive; cause inflammation and shock;
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are required for alcoholic liver cirrhosis; sensitize to radiation damage;
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accelerate formation of aging pigment, cataracts, retinal degeneration;
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promote free radical damage and excitoxicity; cause cancer and accelerate
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its growth; are toxic to the heart muscle and promote atherosclerosis;
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can cause brain edema, diabetes, excessive vascular permeability, precocious
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puberty, progesterone deficiency, skin wrinkling and other signs of
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aging.</p>
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<p>Whether
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any of the claimed pharmaceutical uses of the polyunsaturated oils,
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besides purgation, turn out to be scientifically valid remains to be
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seen. The theoretical bases often used to back up the claimed benefits
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are confused or false, or both.</p>
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<p>People
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who are willing to question the validity of an "orthodox method,"
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such as the glass microelectrode, are in a position to make observations
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that were "forbidden" by the method and its surrounding ideology.
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(See Davis, et al., 1970.) Their perception is freed in ways that could
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lead to new understanding and practical solutions to old problems.</p>
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<p>But
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sometimes experiments seem to be designed as advertising, rather than
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science. Recent studies of the effects of fish oils on night vision
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or development of the retina, for example, seem to forget that fish
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oil contains vitamin A, and that vitamin A has the effects that are
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being ascribed to the unsaturated fatty acids.</p>
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<p>With
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the financial cutbacks in university libraries, there is a risk that
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the giant seed-oil organizations will succeed in using governmental
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power to regulate the alternative communication of scientific information,
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allowing them to control both public and "scientific" opinion
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more completely than they do now. </p>
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<h2>References</h2>
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<small>
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<p>Gilbert
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N. Ling, A Revolution in the Physiology of the Living Cell, Krieger
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Publ., Melbourne, Florida, 1993.</p>
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<p>G.
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W. Fox, Nature 205, 328, 1965; Naturwissenschaften 60, 359, 1973.</p>
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Fleischer, B. Fleischer, and W. Stoeckenius, J. Cell Ciol. 32, 193,
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<p>H.
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</p>
|
|
</small>
|
|
<h2>Notes</h2>
|
|
<small>
|
|
<p>#
|
|
In their preface, Nelson and Cox say their book has retained "Lehninger's
|
|
ground-breaking organization, in which a discussion of biomolecules
|
|
is followed by metabolism and then information pathways," but that
|
|
at every other level "this second edition is a re-creation, rather
|
|
than a revision, of the original text. Every chapter has been comprehensively
|
|
overhauled, not just by adding and deleting information, but by completely
|
|
reorganizing its presentation and content...." This is reminiscent
|
|
of the book published under the name of Max Gerson after his death,
|
|
which inserted essentially fraudulent material to support an approach
|
|
that is exactly what Gerson strongly advised against.</p>
|
|
<p>*
|
|
This principle might be applicable to the removal of calcium from living
|
|
cells, with a procedure that wouldn't have the dangers of chelation.
|
|
Increased consumption of sodium and magnesium should facilitate the
|
|
removal and excretion of abnormally retained calcium. Sodium has been
|
|
found to protect tissues against oxidative damage, for example during
|
|
cancer therapy with cis-platinum.</p>
|
|
</small>
|
|
<hr>
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