The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki
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The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

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CHAPTER 4 An Introduction to Lipid Metabolism When the mitochondrial free radical theory was first conceived, researchers presumed that the process of steady mitochondrial decline was happening independently, and roughly equally, in all cells of a given type. It is now quite certain, however, that the process is very uneven indeed: some cells undergo complete OXPHOS collapse, whereas others apparently undergo none. Moreover, the cells that undergo OXPHOS collapse are extremely few in number. The evidence for the above will be discussed in later chapters. But it has a crucial corollary: if MiFRA is “correct”—that is, if the mechanism that MiFRA proposes is really the main driving force in aging—then these few anaerobic cells must somehow be doing harm to their mitochondrially healthy colleagues, or else there would be no macroscopic (that is, tissue-wide) consequences of it. The mechanism for this that I believe to be the most plausible, and which will be presented in Chapter 9, is a side-effect of the body’s systems for moving lipids—fats and related molecules—between tissues. An introduction to these systems is therefore necessary. 4.1. The Major Fat-Related Molecules in Cells: Structural Roles We saw in Section 2.3.2.3 that fats in the diet can be broken down and fed, two carbon atoms at a time, into the same metabolic pathway that derives energy from breaking down sugars. But, unlike sugars, fats and related molecules also have a fundamental structural role in cells. They are the building blocks of membranes—cell membranes, mitochondrial membranes, and many others. All these molecules—the fats and the related molecules—are collectively termed lipids. Most of the structural molecules in membranes are in fact not exactly fat molecules: they are modified in a generic way. A fat molecule is a triglyceride: a molecule of glycerol with a many-carbon organic acid attached to each of its three carbons. When a fat molecule is broken down, the acids are stripped off and fed into the tricarboxylic acid cycle as described in Section 2.3.2.3. When a fat molecule is to be used in a membrane, however, only one of the three chains is removed; also, rather than being replaced by a hydrogen atom, it is replaced by a group centred around a phosphorus atom. The resulting molecule is called a phospholipid. Two phospholipids can thus differ in the nature of the phosphorus-centered group (the head group) and/or in the two fatty-acid side chains that are retained (see Fig. 4.1). Neither makes an enormous difference to the chemistry of the molecule, but differences in the head groups have more effect on that than differences in the side chains, so the nomenclature of phospholipids is based on the head groups. (The head groups of membrane phospholipids also have different effects on the surrounding water: we will return to this in Sections 11.2 and 11.3.) What the side chains do affect is the physical properties of a membrane made of phospholipids: if one of the chains is polyunsaturated (contains two or more C=C double bonds) then the molecule takes up more room, so a membrane with large amounts of that type of phospholipid is more fluid than otherwise, which is a property The Mitochondrial Free Radical Theory of Aging, by Aubrey D.N.J. de Grey. ©1999 R.G. Landes Company.

48 The Mitochondrial Free Radical Theory of Aging Fig. 4.1. Some types of lipid (and their components) prevalent in biological systems.

48<br />

<strong>The</strong> <strong>Mitochondrial</strong> <strong>Free</strong> <strong>Radical</strong> <strong>The</strong>ory <strong>of</strong> <strong>Aging</strong><br />

Fig. 4.1. Some types <strong>of</strong> lipid (and their components) prevalent in biological systems.

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