Human Metabolism. Keith N. Frayn

effects on the serum cholesterol concentration and propensity to heart disease will be discussed.

It will be seen from Figures 1.4 and 1.9 that saturated fatty acids, such as palmitic (16:0), have a natural tendency to fit together in nice orderly arrays. The unsaturated fatty acids, on the other hand, have less regular shapes (Figure 1.9). This is reflected in the melting points of the corresponding triacylglycerols – saturated fats, such as beef suet with a high content of stearic acid (18:0), are relatively solid at room temperature, whereas unsaturated fats, such as olive oil, are liquid. This feature may have an important role in metabolic regulation, although its exact significance is not yet clear. We know that cell membranes with a high content of unsaturated fatty acids in their phospholipids are more ‘fluid’ than those with more saturated fatty acids. This may make them better able to regulate metabolic processes – for instance, muscle cells with a higher content of unsaturated fatty acids in their membranes respond better to the hormone insulin, probably because the response involves the movement of proteins (insulin receptors, glucose transporters) within the plane of the membrane (discussed in Boxes 3.2, 3.4, and elsewhere), and this occurs faster if the membrane is more fluid.

Figure 1.9 Pictures of the molecular shapes of different fatty acids. (a) saturated fatty acid, stearic acid (18:0), showing a straight chain; (b) mono-unsaturated fatty acid, oleic acid (18:1 n-9), showing a ‘bend’ in the chain at the double bond. Source: from Gurr, M. I., Harwood, J. L., Frayn, K. N., Murphy, D. J., & Michell, R. H. (2016). Lipids – Biochemistry, Biotechnology and Health. 6th edn. Oxford: Wiley.

An important feature of the fatty acids is that, as their name implies, they have within one molecule both a hydrophobic tail and a polar carboxylic acid group. Long-chain fatty acids (12 carbons and more) are almost insoluble in water. They are carried in the plasma loosely bound to the plasma protein albumin. Nevertheless, they are more water miscible than triacylglycerols, which are carried in plasma in the complex structures known as lipoproteins (discussed fully in Chapter 10). The simpler transport of NEFAs is perhaps why they serve within the body as the immediate carriers of lipid energy from the stores to the sites of utilisation and oxidation; they can be released fairly rapidly from stores when required and their delivery to tissues is regulated on a minute-to-minute basis.

But NEFAs would not be a good form in which to store lipid fuels in any quantity. Their amphipathic nature means that they aggregate in micelles (small groups of molecules, formed with their tails together and their heads facing the aqueous environment); they would not easily aggregate in a very condensed form for storage. They would also disrupt structural lipids such as those found in membranes. Triacylglycerols, on the other hand, aggregate readily; these hydrophobic molecules form uniform lipid droplets from which water is completely excluded, and which are an extremely efficient form in which to store energy (in terms of kJ stored per gram weight). This is illustrated in Figure 1.10. Thus, triacylglycerols are the form in which fat is mostly stored in the human body, and indeed in the bodies of other organisms; hence they are the major form of fat in food. NEFAs, on the other hand, are the form in which lipid energy is transported in a highly regulated manner from storage depots to sites of utilisation and oxidation.

Figure 1.10 Comparison of fat and carbohydrate as fuel sources. Raw potatoes (right) are hydrated to almost exactly the same extent as glycogen in mammalian cells. Olive oil (left) is similar to the fat stored in droplets in mature human adipocytes. The potatoes (1.05 kg) and olive oil (90 g) here each provide 3.3 MJ on oxidation. This emphasises the advantage of storing most of our energy in the body as triacylglycerol rather than as glycogen.

      1.2.2.3 Proteins

      Proteins are chains of amino acids linked through peptide bonds. Individual proteins are distinguished by the number and order of amino acids in the chain – the sequence, or primary structure. Within its normal environment, the chain of amino acids will assume a folded, three-dimensional shape, representing the secondary structure (local folding into α-helix and β-sheet) and tertiary structure (folding of the complete chain on itself). Two or more such folded peptide chains may then aggregate (quaternary structure) to form a complete enzyme or other functional protein.

In terms of energy metabolism, the first aspect we shall consider is not how this beautiful and complex arrangement is brought about; we shall consider how it is destroyed. Protein in food is usually denatured (its higher-order structures disrupted) by cooking or other treatment, and then within the intestinal tract the disrupted chains are broken down to short lengths of amino acids before absorption into the bloodstream. Within the bloodstream and within tissues we shall be concerned with the transport and distribution of individual amino acids. These are mostly sufficiently water soluble to circulate freely in the aqueous environment of the plasma. Only tryptophan is sufficiently hydrophobic to require a transporter; it is bound loosely (like the NEFAs) to albumin. Amino acids, not surprisingly, do not cross cell membranes by simple diffusion; there are specific transporters, carrying particular groups of amino acids (Chapter 2, Table 2.2).

      Protein is often considered as the structural material of the body, although it should not be thought of as the only structural material; it can only assume this function because of the complex arrangements of other cellular constituents, especially phospholipids forming cell membranes. Nevertheless, apart from water, protein is the largest single component in terms of mass of most tissues.¹ Within the body, the majority of protein is present in the skeletal muscles, mainly because of their sheer weight (around 40% of the body weight) but also because each muscle cell is well packed with the proteins (actin and myosin) which constitute the contractile apparatus. But it is important to remember that most proteins act in an aqueous environment and are, therefore, associated with water. This is relevant if we consider the body’s protein reserves as a form of stored chemical energy. Since protein is associated with water, it suffers the same drawback as a form of energy storage as does glycogen; with every gram of protein are associated about 3g of water. It is not an energy-dense storage medium. Further, although protein undoubtedly represents a large source of energy that is drawn upon during starvation, it should be remembered that there is, in animals, no specific storage form of protein; all proteins have some function other than storage of energy. Thus, utilisation of protein as an energy source involves loss of the substance of the body. In evolutionary terms we might expect that this will be minimised (i.e. the use of the specific storage compounds glycogen and triacylglycerol will be favoured) and, as we shall see in later chapters, this is exactly the case.

The monomers from which proteins are made, amino acids, have important