Membranes, plasma membranes, and surfaces
by Raymond Peat
The “essential fatty acids”:
Suppress metabolism and promote obesity; are immunosuppressive; cause inflammation and shock; are required for alcoholic liver cirrhosis; sensitize to radiation damage; accelerate formation of aging pigment, cataracts, retinal degeneration; promote free radical damage and excitoxicity; cause cancer and accelerate its growth; are toxic to the heart muscle and promote atherosclerosis; can cause brain edema, diabetes, excessive vascular permeability, precocious puberty, progesterone deficiency….
必需脂肪酸:
抑制新陈代谢,促进肥胖;免疫抑制;引起炎症和休克;酒精性肝硬化患者需要的;对辐射损伤敏感;加速老化色素的形成、白内障、视网膜退化;促进自由基损伤和兴奋性;导致癌症并加速其生长;对心肌有毒并促进动脉粥样硬化;会不会引起脑水肿、糖尿病、血管通透性过强、性早熟、黄体酮缺乏….
Twice, editors have printed my articles on unsaturated fats, with adjoining “rebuttals,” but I was disappointed that all of my points were ignored, as if you could rebut an argument by just saying that you emphatically disagree with it. I think it is evident that those people don't know what would be involved in refuting an argument. They are annoyed that I have bothered them with some evidence, but not sufficiently annoyed to cause them to try to marshal some evidence against my arguments.
Marketing and medical claims are intertwined with a view of life that permeates our culture. I am aware that my criticism of the doctrine of the essentiality of linoleic acid threatens the large profits of many people, and threatens the prestige of the most popular “theory of cell structure,” but I think it is important to point out that nutritional and medical advice depend on the truth of the theory of cell structure and function which supports that advice, and so it is reasonable to see how sound that theory is.
有两次,编辑们发表了我关于不饱和脂肪的文章,附带着“反驳”,但令我失望的是,我所有的观点都被忽视了,就好像你可以反驳一个论点,只要说你断然反对它。我认为很明显,那些人不知道反驳一个论点会涉及到什么。他们很恼火,因为我用一些证据打扰了他们,但还没有恼怒到让他们试图整理一些证据来反对我的论点。
营销和医疗主张与渗透在我们文化中的人生观交织在一起。我意识到,我对亚油酸重要性学说的批评,威胁到许多人的巨额利润,威胁到最流行的“细胞结构理论”的声望,但我认为重要的是,营养和医学建议取决于支持该建议的细胞结构和功能理论的真实性,所以我们有理由看到该理论的合理性。
As I understand it, the doctrine of the “essential fatty acids” goes this way:
1. They are essential because they are required for making cell membranes and prostaglandins.
2. Rats deprived of the unsaturated fatty acids develop a skin disease, and “lose water” through the skin.
3. Human skin diseases (etc.) can be cured with polyunsaturated fats.
In fact, rats may get a skin disease when fed a fat-free diet, but the observation that vitamin B6 cures it should have laid to rest the issue of the dietary essentiality of the polyunsaturated oils more than 50 years ago. Scientifically, it did, but forces greater than science have revivified the monster. Experiments that confirm the disproof are done periodically–animals living generation after generation without unsaturated oils in their diet or any evidence of harm, human cells growing in culture-dishes without polyunsaturated fats, for example–without noticeable effect on the doctrine, which is perpetuated in many effective, nonscientific ways–textbooks, advertisements, college courses, for example.
根据我的理解,“必需脂肪酸”的原则是这样的:
1. 它们是必不可少的,因为它们是制造细胞膜和前列腺素所必需的。
2. 缺乏不饱和脂肪酸的老鼠会患上皮肤病,并通过皮肤“流失水分”。
3.人类皮肤病(等)可以用多不饱和脂肪治疗。
事实上,老鼠在吃无脂饮食时可能会患上皮肤病,但观察到维生素B6能治愈这种疾病,早在50多年前就应该解决饮食中多不饱和油脂的重要性问题了。科学上的确如此,但比科学更强大的力量使怪物复活了。定期完成实验,证实了反证,动物生活一代又一代没有不饱和油脂在他们的饮食或任何损害的证据,人类细胞生长在培养皿中没有多不饱和脂肪,例如对教义——没有明显的影响,这是在许多有效的延续,非科学的方式——比如教科书、广告、大学课程。
Now, instead of demonstrating harm from a dietary lack of the “essential” fats, the presence of the Mead acid or omega-9 fatty acids is taken as evidence of a deficiency. Our cells (and animal cells) produce these unsaturated fats when their special desaturase enzymes are not suppressed by the presence of exogenous linoleic or linolenic acids. Normally, the inactivation of an enzyme system and the suppression of a natural biological process might be taken as evidence of toxicity of the vegetable oils, but here, the occurrence of the natural process is taken as evidence of a deficiency. To me, this seems very much like the “disease” of having tonsils, an appendix, or a foreskin–if it is there, you have a problem, according to the aggressive surgical mentality. But what is the “problem” in the case of the natural Mead or omega-9 acids? (I think the “problem” is simply that they allow us to live at a higher energy level, with greater resistance to stress, better immunity, and quicker healing.)
There have been arguments based on “membranes” and on prostaglandins. The absence of “good” prostaglandins would seem to be an obvious problem, except that the “good” prostaglandins always turn out to have some seriously bad effects when examined in other contexts. Animals that lack dietary unsaturated fats appear to escape most of the problems that are associated with prostaglandins, and I think this means that many of the toxic effects of the unsaturated vegetable oils result from the quantity and type of “eicosanoid”/lipoxygenase products made from them.
One type of membrane argument had to do with the fragility of red blood cells, reasoning, apparently, that the cells are “held together” by a lipid bilayer membrane. (Just what is the tensile strength of a lipid bilayer? Why do fatty acids or saponins weaken blood cells, instead of reinforcing them? If the “tensile strength” of a lipid layer exists, and is positive rather than negative, it is negligible in relation to the tensile strength of the cytoplasm.) Another type of :“membrane” argument was that the mitochondria are abnormal when animals don't get the essential fatty acids in their diet, because the mitochondria are supposed to be essentially membranous structures containing the essential fatty acids. (Actually, the deficient mitochondria produce more ATP than do mitochondria from animals fed the vegetable oils.) Another argument is that “membrane fluidity” is a good thing, and that unsaturated essential fatty acids make the membranes more fluid and thus better–by analogy with their lower bulk-phase melting temperature. (But the measure of fluidity is a very limited thing on the molecular level, and this fluidity may be associated with decreased cellular function, instead of the postulated increase.)
现在,米德酸或欧米加-9脂肪酸的存在被认为是缺乏“必需”脂肪的证据,而不是证明饮食中缺乏“必需”脂肪的危害。我们的细胞(和动物细胞)产生这些不饱和脂肪时,它们的特殊去饱和酶不受外源亚油酸或亚麻酸的抑制。正常情况下,酶系统的失活和自然生物过程的抑制可以被认为是植物油毒性的证据,但在这里,自然过程的发生被认为是缺乏的证据。对我来说,这看起来很像扁桃体、阑尾或包皮的“疾病”——如果它在那里,你就有问题,根据激进的外科思想。但是,天然的米德或欧米茄9酸的“问题”是什么呢?(我认为“问题”很简单,它们让我们生活在更高的能量水平,更强的抗压力,更好的免疫力,更快的康复。)
有一些基于“膜”和前列腺素的争论。“好”前列腺素的缺乏似乎是一个明显的问题,除了“好”前列腺素在其他情况下总是有一些严重的坏影响。动物缺乏不饱和脂肪的饮食似乎逃脱大多数与前列腺素相关的问题,我认为这意味着许多毒性作用的不饱和植物油源于“类二十烷酸/脂肪氧合酶的数量和类型产品。
一种关于细胞膜的争论与红血球的脆弱性有关,显然,他们认为这些细胞是由一层脂质双分子膜“连接在一起”的。(脂质双分子层的抗张强度是多少?为什么脂肪酸或皂苷会削弱而不是增强血细胞?如果脂质层的“拉伸强度”存在,并且是正的而不是负的,那么它与细胞质的拉伸强度相比是可以忽略不计的。)另一种:“膜”论点是,当动物在饮食中得不到必需脂肪酸时,线粒体就会异常,因为线粒体本质上应该是包含必需脂肪酸的膜结构。(事实上,缺乏的线粒体产生的ATP比食用植物油的动物线粒体产生的ATP要多。)另一个论点是,“膜流动性”是一个好东西,不饱和必需脂肪酸使膜更流动,因此更好——通过类比它们较低的体相熔化温度。(但在分子水平上,对流动性的测量是非常有限的,这种流动性可能与细胞功能下降有关,而不是假定的增加。)
The most addled sort of argument about “membranes” is that animals on the diet lacking polyunsaturated oils have skin that is unable to retain water because of “defective cell membranes.” The skin's actual barrier function is the result of mulptile layers of keratinized (“cornified,” horny) cells, which have become specialized by their massive production of the protein keratin–very much as red blood cells become specialized by producing the protein, hemoglobin. Since these cells lose most of their water as they become horny, the issue of whether they still have a “plasma membrane” seems to have little interest to researchers; the same can be said regarding the cells of hair and nails. After the epidermal cells have become keratinized and inert, the sebaceous glands in the skin secrete oils, which are absorbed by the dense, proteinaceous cells, causing increased resistance to water absorption. The ideas of a plasma membrane on the cell, and of the water-barrier function of the skin, are two distinct things, that have been blurred together in a thoughtless way. It has been suggested that vitamin B6 cures the characteristic skin disorder of a vitamin B6 deficiency by altering fat metabolism, but the vitamin is involved in cell division and many other processes that affect the skin.
Given the fact that the “essential” oils aren't essential for the growth of cells, they can't be essential for making plasma membranes (if cells must have plasma membranes), or mitochondrial membranes, or any kind of membrane, but as long as there is the idea that fats mainly have the function of building membranes, someone is going to argue that membranes containing vegetable oils are more fluid, or more youthful, or more sensitive, or better in some way than those containing Mead acids, palmitic acid, oleic acid, stearic acid, etc.
关于“细胞膜”最混乱的一种争论是,饮食中缺乏多不饱和油的动物,由于“细胞膜有缺陷”,皮肤无法保持水分。皮肤真正的屏障功能是多层角质化细胞的结果,这些细胞通过大量生产角蛋白而特化,就像红细胞通过生产蛋白质、血红蛋白而特化一样。由于这些细胞在变成角质时失去了大部分水分,研究人员似乎对它们是否仍有“质膜”的问题没什么兴趣;头发和指甲的细胞也是如此。当表皮细胞变得角质化和惰性后,皮肤中的皮脂腺分泌油脂,这些油脂被致密的蛋白质细胞吸收,从而增加了皮肤的吸水阻力。细胞上的质膜和皮肤的水屏障功能是两个截然不同的概念,它们被轻率地混淆在一起。有人认为,维生素B6可以通过改变脂肪代谢来治疗因缺乏维生素B6而导致的典型皮肤疾病,但维生素参与了细胞分裂和许多其他影响皮肤的过程。
考虑到“基本”油不是必不可少的细胞的生长,不能形成等离子体膜(如果细胞必须有等离子体膜),或线粒体膜,或任何类型的膜,但只要有脂肪的功能主要有建筑膜,有人会说,含有植物油的膜更流动,更年轻,更敏感,或者在某些方面比含有米德酸,软脂酸,油酸,硬脂酸等的膜更好。
For over a century, people have suggested that cells are enclosed in an oily membrane, because there are higher or lower concentrations of many water-soluble substances inside cells, than in the blood, lymph, and other extracellular fluids, and the idea of a membrane was invoked (W. Pfeffer, 1877; E. Overton, 1895, 1902) to explain how that difference can persist. (By 1904, the idea of a membrane largely made of lecithin was made ludicrous by A. Nathansohn's observation that water-soaked lecithin loses its oily property, and becomes very hydrophilic; the membrane was supposed to exclude water-soluble molecules while admitting oil-soluble molecules.)
Inside the cell membrane, the cell substance was seen as a watery solution. Biochemistry, as a profession, was strongly based on the assumption that, when a tissue is ground up in water, the dilute extract closely reflects the conditions that existed in the living cell. Around 1970, when I tried to talk to biochemists about ways to study the chemistry of cells that would more closely reflected the living state, a typical response was that the idea was ridiculous, because it questioned the existence of biochemistry itself as a meaningful science.. But since then, there has been a progressive recognition that organization is more important in the life of a cell than had been recognized by traditional biochemistry. Still, many biochemists thoughtlessly identify the chemistry of the living cell with their study of the water-soluble enzymes, and relegate the insoluble residue of the cell to “membrane-associated proteins” or, less traditionally, to “structural proteins.” It has been several decades since the structural/contractile protein of muscle was found to be an enzyme, an ATPase, but the idea that the cell itself is a sort of watery solution, in which the water-soluble enzymes float, randomly mingling with dissolved salts, sugars, etc., persists, and makes the idea of a semipermeable membrane seem necessary, to separate a “watery internal phase” from the watery external phase. Physical chemists have no trouble with the fact that a moist protein can absorb oil as well as water, and the concept that even water-soluble enzymes have oil-loving interiors is well established. If that physical-chemical information had existed in Overton's time, there would have been no urge to postulate an oily membrane around cells, to allow substances to pass into them, in proportion to their solubility in oil.
一个多世纪以来,人们一直认为细胞被包裹在一层油性膜中,因为与血液、淋巴和其他细胞外液体相比,细胞内的许多水溶性物质的浓度或高或低,于是就引出了膜的概念(W. Pfeffer, 1877;E. Overton, 1895, 1902)来解释这种差异是如何持续存在的。(到1904年,由于a . Nathansohn的观察,细胞膜主要由卵磷脂构成的想法被认为是可笑的,因为水浸泡的卵磷脂失去了它的油性,变得非常亲水;膜应排除水溶性分子,接纳油溶性分子)。
在细胞膜内部,细胞物质被看作是水溶液。生物化学作为一门专业,是基于这样一种假设:当一个组织在水中被碾碎时,稀释后的萃取物紧密地反映了活细胞中存在的条件。大约在1970年,当我试图与生化学家讨论研究细胞化学的方法,以更密切地反映生命状态时,一个典型的反应是,这种想法是荒谬的,因为它质疑生物化学本身作为一门有意义的科学的存在。但从那时起,人们逐渐认识到,在细胞的生命中,组织比传统生物化学所认识到的更为重要。尽管如此,许多生物化学家还是轻率地将活细胞的化学性质与他们对水溶性酶的研究联系起来,并将细胞的不溶性残基归为“膜相关蛋白”,或者不那么传统地归为“结构蛋白”。已经有几十年的结构/肌肉收缩蛋白被发现一种酶,atp酶,但认为细胞本身是一种水解决方案,水溶性酶浮动,随机混合溶解的盐,糖,等等,持续下去,并使半透膜的想法似乎有必要,将“含水的内部相”与含水的外部相分离。物理化学家对潮湿的蛋白质既能吸收水也能吸收油这一事实没有异议,而且水溶性的酶也有亲油的内部结构这一概念已被广泛认可。如果在奥弗顿的时代存在这种物理化学信息,就不会迫切地假定细胞周围有一层油膜,让物质按照它们在油中的溶解度比例进入细胞。
Because biochemists like to study their enzymes in watery test-tube solutions, they find it easy to think of the cell-substance as a watery solution. With that belief, it is natural that they prefer to think of the primeval ocean as where life originated. Their definitions of chemical reactions and equilibria in the water-phase (and by extension in cells) ignore the alternative reactions and equilibria that would occur in an environment in which ordinary water was not the dominant medium. By this failure to consider the alternatives, they have created some problems that are hard to explain. For example, the polymerization of amino acids into protein is energetically expensive in water, but it is spontaneous in a relatively dry environment, and this spontaneous reaction creates non-random structures with the capacity for building larger structures, with stainable bilayer “membranes,” and with catalytic action. (Sidney Fox, 1965, 1973.) Similarly, the problem of ATP synthesis essentially disappears when it is considered in an environment that controls water. The scientific basis for the origin of life in a “primeval soup” never really existed, and more people are now expressing their scepticism.
However, biochemists have their commitments:
“In the course of biological evolution, one of the first developments must have been an oily membrane that enclosed the water-soluble molecules of the primitive cell, segregating them and allowing them to accumulate to relatively high concentrations. The molecules and ions contained within a living organism differ in kind and in concentration from those in the organism's surrounding.” (Principles of Biochemistry, supposedly by Lehninger, Nelson, and Cox, though Lehninger is dead and I think his name is attached to it to exploit his fame.# Worth Publishers, 1993.)
Hair is composed of thoroughly dead cells, but if it is washed until it contains no sodium or potassium, and then dipped in serum, or a solution of sodium and potassium, it takes up much more potassium than sodium, in the way a living cell does, concentrating potassium “against the gradient.” That is the sort of behavior that led to the postulation of a plasma membrane, to maintain the organization that was created by expending energy. “Membrane pumps” use energy, supposedly, to establish the concentration difference, and the barrier membrane keeps the solutes from diffusing away. The lipid bilayer membrane was an early guess, and the pumps were added later, as needed. Gilbert Ling reviewed the published studies on the various “membrane pumps,” and found that the energy needed to operate them was 15 times greater than all the energy the cell could possibly produce.
因为生物化学家喜欢在水的试管溶液中研究酶,他们发现很容易把细胞物质想象成水的溶液。有了这种信念,他们自然更愿意认为原始海洋是生命起源的地方。他们对水相中的化学反应和平衡的定义(以及细胞中的化学反应和平衡)忽略了在普通水不是主要介质的环境中可能发生的替代反应和平衡。由于没有考虑替代方案,他们造成了一些难以解释的问题。例如,氨基酸在水中聚合成蛋白质的能量消耗很大,但在相对干燥的环境中是自发的,这种自发反应产生了非随机结构,具有构建更大结构的能力,具有可染色的双层“膜”,并具有催化作用。(西德尼·福克斯,1965,1973)。同样地,ATP合成的问题在控制水的环境中也基本消失了。生命在“原始汤”中起源的科学依据从未真正存在过,现在越来越多的人表达了他们的怀疑。
然而,生物化学家有他们的承诺:
“在生物进化的过程中,最初的发展之一肯定是一种油膜,它将原始细胞的水溶性分子包裹起来,将它们分离出来,使它们积累到相对较高的浓度。生物体内的分子和离子在种类和浓度上都不同于其周围的生物。”(《生物化学原理》,据推测是由Lehninger, Nelson和Cox写的,尽管Lehninger已经去世了,我认为他的名字和它联系在一起是为了利用他的名声。# Worth Publishers, 1993.)
头发是彻底的死细胞组成,但如果是洗到不含钠或钾,然后蘸血清,或解决方案的钠和钾,它占用更多的钾钠,钾在一个活细胞的方式,集中对梯度”。正是这种行为导致了质膜的假设,它维持着通过消耗能量而形成的组织。据推测,“膜泵”利用能量来建立浓度差,而屏障膜阻止溶质扩散。脂质双分子层膜是一个早期的猜测,泵是后来根据需要添加的。Gilbert Ling回顾了已发表的关于各种“膜泵”的研究,发现运行它们所需的能量是细胞可能产生的全部能量的15倍。
Water softeners contain an ion-exchange resin, that uses the same principle hair does to concentrate ions, which is simply a selectivity based on the acidity of the resin, and the size of the ion. The resin binds calcium more strongly than it binds sodium, and so the water gives up its calcium in exchange for sodium.* Gilbert Ling devised many experiments that demonstrated the passivity of ion-accumulation by living cells.
Usually, cells are surrounded by and imbedded in materials that they have secreted, and their surfaces are often covered with materials that, while remaining anchored to the cell, have a considerable affinity for water. Physically, many of the molecules attached to cells are “surfactants,” making the cell wettable, though it isn't customary to describe them as such. The glycoproteins that give cells their characteristic immunological properties are among these materials. At a certain point, there is a transition between the “outside” of the cell, which is relatively passive and water-friendly, and the cell itself, in which water is subordinated to the special conditions of the cell. (The postulated lipid bilayer membrane, in contrast, has two phase discontinuities, one where it meets the cytoplasm, another where it meets the outside world.) At this phase boundary, between two different substances, it is normal to find an electrical potential difference. When two electrically different substances are in contact, it isn't surprising to find an electrical double-layer at the surface. This is a passive process, which doesn't take any energy to maintain, but it can account for specific arrangements of molecules in the region of the phase boundary, since they are exposed to the electrical force of the electrical double-layer. That is to say that in a completely inert and homogeneous substance, a “surface structure” will be generated, as a result of the electrical difference between that substance and the adjoining substance. (This surface structure, if it is to be described as a membrane, must be called a “wet membrane,” while the lipid bilayer would be a “dry membrane,” since exclusion of water is its reason for existing.) Too many biologists still talk about “electrogenic membrane pumps,” indicating that they haven't assimilated the results of Gilbert Ling's research.
To say it another way, there are several kinds of physical process that will govern the behavior of fats, and fats of different types will interact in different ways with their environments. They interact complexly with their environment, serving in many cases as regulatory signal-substances. To describe their role as “membranes” is worse than useless.
软水器含有一种离子交换树脂,它使用与头发浓缩离子相同的原理,只是根据树脂的酸度和离子的大小进行选择性。树脂与钙的结合比与钠的结合更强,所以水放弃了钙来交换钠。Gilbert Ling设计了许多实验来证明活细胞离子积累的被动性。
通常情况下,细胞被它们分泌的物质包围和包围,它们的表面通常被固定在细胞上的物质所覆盖,这些物质对水有相当大的亲和力。从物理上讲,许多附着在细胞上的分子都是“表面活性剂”,使细胞具有可湿性,尽管人们并不习惯这样描述它们。赋予细胞特有免疫学特性的糖蛋白就是这些物质之一。在某种程度上,细胞的“外部”是相对被动的、亲水的,而细胞本身则服从于细胞的特殊条件。(相反,假定的脂质双分子层膜有两个相不连续,一个在与细胞质接触的地方,另一个在与外界接触的地方。)在两种不同物质的相界处,找到电位差是正常的。当两种电性不同的物质接触时,在其表面发现一个电性双层是不足为奇的。这是一个被动的过程,不需要任何能量来维持,但它可以解释在相边界区域分子的特定排列,因为他们暴露在电双层的电力之下。也就是说,在一个完全惰性和均匀的物质中,由于该物质和相邻物质之间的电差异,将产生一个“表面结构”。(这种表面结构,如果要描述为膜,必须称为“湿膜”,而脂质双分子层将是“干膜”,因为它的存在原因是不含水。)太多的生物学家仍然在谈论“电致膜泵”,这表明他们还没有吸收Gilbert的研究结果。
换句话说,有几种物理过程会控制脂肪的行为,不同类型的脂肪会以不同的方式与环境相互作用。它们与环境复杂地相互作用,在许多情况下充当调节信号物质。把它们描述成“膜”比无用更糟糕。
Cells can be treated with solvents to remove practically all fats, yet the cells can still show their characteristic membranes: Plasma membrane, mitochondrial membranes, even the myelin figures. The proteins that remain after the extraction of the fats appear to govern the structure of the cell.
A small drop of water can float for a moment on the surface of water; this is explained in terms of the organization of the water molecules near the surface. No membrane is needed to explain this reluctance to coalesce, even though water has a very high affinity for water.
People believed in the “lipid bilayer membrane” for decades before the electron microscope was able to produce an image that could be said to correspond to that theoretical structure. Osmic acid, which is believed to stain fats, does produce a double layer at the surface of cells. However, the arrangement of fat molecules in the lipid bilayer is such that the fatty tails of the two layers are touching each other, while their acidic heads are pointed away from each other. A lipid bilayer, in other words, contains a single zone of fat, bounded by two layers of acid. The “fat-staining” property of osmic acid, then, argues against the lipid bilayer structure.
Osmic acid is very easily reduced electrically, forming a black product. Proteins with their sulfur molecules in a reduced state, for example, would cause an osmium compound to be deposited, and the appearance of two layers of osmium at the cell's phase boundary would be compatible with the idea of an electrical double-layer, induced in proteins.
细胞可以用溶剂处理,除去几乎所有的脂肪,但细胞仍然可以显示出它们特有的膜:质膜、线粒体膜,甚至是髓磷脂。从脂肪中提取出来的蛋白质似乎控制着细胞的结构。
一小滴水可以在水面上漂浮一会儿;这可以用地表附近水分子的组织来解释。不需要膜来解释这种不愿结合的现象,即使水对水有很高的亲和力。
人们相信“脂质双分子层膜”的存在已经有几十年了,直到电子显微镜能够显示出与理论结构相对应的图像。锇酸被认为可以染色脂肪,但它确实能在细胞表面产生双层结构。然而,脂质双分子层中脂肪分子的排列是这样的:两层脂肪层的尾部互相接触,而它们的酸性头部则彼此远离。一个脂质双分子层,换句话说,包含一个由两层酸包围的单一脂肪区。因此,锇酸的“脂肪染色”特性与脂质双层结构相矛盾。
锇酸很容易电还原,形成黑色产物。例如,处于还原状态的蛋白质中的硫分子会导致锇化合物的沉积,在细胞的相边界出现两层锇,这与在蛋白质中诱导形成电双层的想法是一致的。
Electrically charged proteins, which are able to interact with glutathione to increase or decrease their degree of reduction/electrical charge, distributed throughout the cytoplasm, would explain another feature of osmic acid staining, which is incompatible with the “fat-staining” concept. Asphyxia increases the stainability of cells with osmic acid, and this change seems to represent the availability of electrons, rather than the distribution of fats, since the change can appear within 3 minutes. (C. Peracchia and J. D. Robertson, “Increase in osmiophilia of axonal membranes of crayfish as a result of electrical stimulation, asphyxia, or treatment with reducing agents,” J. Cell Biol. 51, 223, 1971; N. N. Bogolepov, Ultrastructure of the Brain in Hypoxia, Mir, Moscow, 1983) The amino groups of proteins might also be stained by osmic acid, though asphyxia would more directly affect the disulfide groups. The increased staining with silver in asphyxia similarly suggests an increase in sulfhydryls.
Freezing cells, and then fracturing them and coating the fragments with metal or carbon is often used to “demonstrate the lipid bilayer,” so it is interesting that the osmium compound that “reveals” the lipid bilayer for the electron microscope destroys the apparent membrane in the freezing technique. (R. James and D. Branton, “The correlation between the saturation of membrane fatty acids and the presence of membrane fracture faces after osmium fixation,” Biochim. Biophys. Acta 233, 504-512, 1971; M. V. Nermut and B. J. Ward, “Effect of fixatives on fracture plane in red blood cells,” J. Microsc. 102, 29-39, 1974.)
So, when someone says “we need the essential fatty acids to make cell membranes,” my response is likely to be “no, we don't, and life probably originated on hot lava and has never needed lipid membranes.”
On the third argument, that vegetable oils can be used therapeutically, I am likely to say yes, they do have some drug-like actions, for example, linseed oil has been used as a purgative, but as with any drug you should make sure that the side effects are going to be acceptable to you. Currently, it is popular to recommend polyunsaturated oils to treat eczema and psoriasis. These oils are immunosuppressive, so it is reasonable to think that there might be some pleasant consequences if a certain immunological process is suppressed, but they are also intimately involved with inflammation, sensitivity to ultraviolet light, and many other undesirable things. The traditional use of coal tar and ultraviolet light was helpful in suppressing eczema and psoriasis, but its tendency to cause cancer has led many people to forego its benefits to protect their health.
带电的蛋白质能够与谷胱甘肽相互作用,增加或减少它们分布在细胞质中的还原/电荷,这可以解释渗透酸染色的另一个特征,这与“脂肪染色”的概念是不相容的。窒息增加了渗透酸对细胞的耐受性,这种变化似乎代表了电子的可用性,而不是脂肪的分布,因为这种变化可以在3分钟内出现。(C. Peracchia和J. D. Robertson,“电刺激、窒息或还原剂治疗导致小龙虾轴突膜嗜氧性增加”,J. Cell Biol. 51,223, 1971;N. N. Bogolepov, the Ultrastructure of the Brain in Hypoxia, Mir, Moscow, 1983)蛋白质的氨基也可能被锇酸染色,尽管窒息对二硫基的影响更直接。窒息时银染色的增加同样表明巯基的增加。
冷冻细胞,然后将其破碎,并用金属或碳包裹碎片,通常用来“展示脂质双分子层”,所以有趣的是,在电子显微镜下“揭示”脂质双分子层的锇化合物在冷冻技术中破坏了表面的膜。(R. James和D. Branton,“膜脂肪酸饱和与锇固定后膜骨折面存在的相关性”,Biochim。Biophys。Acta photonica sinica, 33,504 - 512,1971;[M. V. Nermut和B. J. Ward,“固定物对红细胞骨折平面的影响”,J. Microsc. 102, 29- 39,1974 .]
所以,当有人说“我们需要必要的脂肪酸来制造细胞膜”时,我的回答很可能是“不,我们不需要,生命可能起源于热熔岩,从来都不需要脂质膜。”
第三个参数,可以使用植物油治疗,我可能会说,是的,他们确实有一些药物样的行动,例如,亚麻籽油已被用作泻药,但与任何药物应该确保副作用会接受你。目前,推荐多不饱和油脂治疗湿疹和牛皮癣的流行。这些油具有免疫抑制作用,因此有理由认为,如果某种免疫过程受到抑制,可能会产生一些令人愉快的结果,但它们也与炎症、对紫外线的敏感性和许多其他不希望发生的事情密切相关。煤焦油和紫外线的传统使用有助于抑制湿疹和牛皮癣,但它有致癌的倾向,导致许多人放弃了它的好处,以保护他们的健康。
If you want to use a polyunsaturated oil as a drug, it is worthwhile to remember that the “essential fatty acids” suppress metabolism and promote obesity; are immunosuppressive; cause inflammation and shock; are required for alcoholic liver cirrhosis; sensitize to radiation damage; accelerate formation of aging pigment, cataracts, retinal degeneration; promote free radical damage and excitoxicity; cause cancer and accelerate its growth; are toxic to the heart muscle and promote atherosclerosis; can cause brain edema, diabetes, excessive vascular permeability, precocious puberty, progesterone deficiency, skin wrinkling and other signs of aging.
Whether any of the claimed pharmaceutical uses of the polyunsaturated oils, besides purgation, turn out to be scientifically valid remains to be seen. The theoretical bases often used to back up the claimed benefits are confused or false, or both.
People who are willing to question the validity of an “orthodox method,” such as the glass microelectrode, are in a position to make observations that were “forbidden” by the method and its surrounding ideology. (See Davis, et al., 1970.) Their perception is freed in ways that could lead to new understanding and practical solutions to old problems.
如果你想用多不饱和脂肪酸油作为药物,值得记住的是,“必需脂肪酸”会抑制新陈代谢,促进肥胖;免疫抑制;引起炎症和休克;酒精性肝硬化患者需要的;对辐射损伤敏感;加速老化色素的形成、白内障、视网膜退化;促进自由基损伤和兴奋性;导致癌症并加速其生长;对心肌有毒并促进动脉粥样硬化;可引起脑水肿、糖尿病、血管通透性过强、青春期早衰、黄体酮缺乏、皮肤起皱等老化迹象。
除了净化作用外,多不饱和油脂的任何声称的药用用途是否在科学上有效还有待观察。通常用来支持声称的好处的理论基础是混淆的或错误的,或两者兼有。
那些愿意质疑“正统方法”(如玻璃微电极)的有效性的人,正处在一种位置上,可以做出被该方法及其周围意识形态“禁止”的观察。(参见Davis等人,1970年)。他们的观念被解放了,这可能导致新的理解和对旧问题的实际解决方案。
But sometimes experiments seem to be designed as advertising, rather than science. Recent studies of the effects of fish oils on night vision or development of the retina, for example, seem to forget that fish oil contains vitamin A, and that vitamin A has the effects that are being ascribed to the unsaturated fatty acids.
With the financial cutbacks in university libraries, there is a risk that the giant seed-oil organizations will succeed in using governmental power to regulate the alternative communication of scientific information, allowing them to control both public and “scientific” opinion more completely than they do now.
但有时实验似乎被设计成广告,而不是科学。例如,最近关于鱼油对夜视或视网膜发育的影响的研究,似乎忘记了鱼油含有维生素A,而维生素A的作用被归因于不饱和脂肪酸。
随着大学图书馆财政的削减,巨大的种子油组织可能会成功地利用政府权力来规范科学信息的替代交流,从而使他们能够比现在更完全地控制公众和“科学”意见。
ADDITIONAL REFERENCES
Gilbert N. Ling, A Revolution in the Physiology of the Living Cell, Krieger Publ., Melbourne, Florida, 1993.
G. N. Ling, “A new model for the living cell: A summary of the theory and experimental evidence for its support,” Int. Rev. Cytol. 26, 1, 1969.
G. N. Ling, A Physical Theory of the Living State, Blaisdell, New York, 1960.
S. W. Fox, Nature 205, 328, 1965; Naturwissenschaften 60, 359, 1973.
S. W. Fox and K. Dose, Molecular Evolution and the Origin of Life, Marcel Dekker, New York, 1977.
S. Fleischer, B. Fleischer, and W. Stoeckenius, J. Cell Ciol. 32, 193, 1967.
H. J. Morowitz and T. M. Terry, Biochem. Biophys. Acta 183, 276, 1969.
L. Napolitano, F. Le Baron, and J. Scaletti, J. Cell Biol. 34, 817, 1967.
F. W. Cope and R. Damadian, “Biological ion exchanger resins: IV. Evidence for potassium association with fixed charges in muscle and brain by pulsed NMR of 39K,” Physiol. Chem. Phys. 6, 17, 1974.
R. Damadian, “Biological ion exchanger resins. III. Molecular interpretations of cellular ion exchange,” Biophys. J. 11, 773, 1971.
R. Damadian, “Biological ion exchanger resins,” Ann. NY Acad. Sci. 204, 211, 1973.
B. V. Deryaguin, “Recent research into the ptroperties of water in thin films and in microcapillaries,” pages 55-60, in The State and Movement of Water in Living Organisms, XIXth Symposium of Soc. Exp. Biol., Cambridge Univ. Press, 1964.
J. S. Clegg and W. Drost-Hansen, “On the density of intracellular water,” J. Biol. Phys. 10, 75-84, 1982.
J. S. Clegg, “Properties and metabolism of the aqueous cytoplasm and its boundaries,” Am. J. Physiol. 26, R133-R151, 1984.
J. S. Clegg, “Intracellular water and the cytomatrix: some methods of study and current views,” J. Cell Biol. 99, 167S-171S, 1984.
W. Drost-Hansen, “Structure and properties of water at biological interfaces,” in Chemistry of the Cell Interface, vol. 2, pages 1-184, H. D. Brown, editor, Academic Press, 1971.
W. Drost-Hansen and J. Clegg, editors, Cell-Associated Water, Academic Press, 1979.
C. F. Hazlewood, “A view of the significance and understanding of the physical properties of cell-associated water,” pages 165-259 in Cell-Associated Water, Drost-Hansen and Clegg, editors, Academic Press, 1979.
P. M. Wiggins, “Water structure as a determinant of ion distribution in living tissue,” J. Theor. Biol. 32, 131-144, 1971.
R. Damadian and F. W. Cope, Physiol. Chem. Phys. 5, 511, 1973.
F. W. Cope, “A review of the applications of solid state physics concepts to biological systems,” J. Biol. Phys. 3, 1 1975.
D. N. Nasonov, Local Reaction of Protoplasm and Gradual Excitation, Israel Program for Scientific Translations, Jerusalem, Office of Technical Services, U.S. Dept.of Commerce, Washington, DC, 1962.
A. Nathansohn, Jahrb. Wiss. Bot. 39, 607, 1904.
A. S. Troshin, Problems of Cell Permeability, Pergamon Press, London, 1966.
A. S. Troshin, Byull. Eksp. Biol. Med. 34, 59, 1952.
I. Tasaki, Nerve Excitation: A Macromolecular Approach, Thomas, Springfield, 1968.
Albert Szent-Gyorgyi, Bioenergetics, Academic Pressn New York, 1957.
Albert Szent-Gyorgyi, The Living State and Cancer, Marcel Deker, New York, 1978.
T. L. Davis, et al., “Potentials in frog cornea and microelectrode artifact,” Amer. J. Physiol. 219(1), 178-183, 1970.
NOTES:
# 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.
* 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.