Spiteller Gerhard
Lehrstuhl Organische Chemie, Universitätsstrasse 30, Bayreuth, Germany.
Med Hypotheses. 2003 Jan;60(1):69-83. doi: 10.1016/s0306-9877(02)00333-x.
Apparently nature uses the unique sensitivity of polyunsaturated fatty acids (PUFAs) versus oxygen to generate chemical signals if the surface of a cell is influenced by an outside or inside event; for instance the attack of microorganisms, proliferation, aging or by treatment of isolated cells with surfactants. It seems that mammalian and plant cells respond equally to such changes in their structures by transformation of polyunsaturated fatty acids localized in the phospholipid layer of the cell wall to lipidhydroperoxides (LOOHs). These lipid peroxidation (LPO) processes involve all PUFAs, not only arachidonic acid.Slight physiological changes of the cell wall for instance by proliferation seem to activate enzymes, e.g., phospholipases and lipoxygenases (LOX). When an outside impact (for instance by attack of microorganisms) exceeds a certain level LOX commit suicide and liberate iron ions. These start a nonenzymatic LPO. Enzymatic and nonenzymatic LPO distinguish fundamentally which has not been recognized in the past. In the enzymatic LPO processes peroxyl radicals generated as intermediates cannot leave the enzyme complex. In contrast in a nonenzymatic LPO process peroxyl radicals are not trapped. They attack nearly any kind of biological molecules, for instance proteins. Thus only the amount of an outside impact decides if proliferation, apoptosis, or necrosis is started. Some evidence indicates that cancer might be the consequence of a low response of cells to induce apoptotic LPO processes. In contrast to high level of LPO processes induces diseases combined with inflammation, for instance rheumatic arthritis. After consumption of food rich in linoleic acid its LPO products become increased in low density lipoprotein (LDL). This LDL is able to enter endothelial cells and damage cells from inside, long before an inflammatory response is detectable.
显然，如果细胞表面受到外部或内部事件的影响，大自然会利用多不饱和脂肪酸（PUFA）对氧气的独特敏感性来产生化学信号；例如微生物的攻击、细胞增殖、衰老或用表面活性剂处理分离的细胞。哺乳动物和植物细胞似乎通过将位于细胞壁磷脂层中的多不饱和脂肪酸转化为脂质氢过氧化物（LOOH），对其结构的这种变化做出相同的反应。这些脂质过氧化（LPO）过程涉及所有多不饱和脂肪酸，而不仅仅是花生四烯酸。细胞壁的轻微生理变化，例如细胞增殖，似乎会激活酶，例如磷脂酶和脂氧合酶（LOX）。当外部影响（例如微生物的攻击）超过一定水平时，LOX会自我毁灭并释放铁离子。这些铁离子引发非酶促LPO。酶促LPO和非酶促LPO在本质上是有区别的，而这在过去并未被认识到。在酶促LPO过程中，作为中间体产生的过氧自由基无法离开酶复合物。相比之下，在非酶促LPO过程中，过氧自由基不会被捕获。它们会攻击几乎任何种类的生物分子，例如蛋白质。因此，只有外部影响的程度决定是启动细胞增殖、凋亡还是坏死。一些证据表明，癌症可能是细胞对诱导凋亡性LPO过程反应低下的结果。与高水平的LPO过程相反，低水平的LPO过程会引发与炎症相关的疾病，例如风湿性关节炎。食用富含亚油酸的食物后，其LPO产物在低密度脂蛋白（LDL）中会增加。这种LDL能够进入内皮细胞并从内部损伤细胞，早在炎症反应可检测到之前就会发生。
