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Simple carbohydrates have the empirical formula C_n(H₂O)_n; complex carbohydrates have an empirical formula which is similar to this (e.g. C_n(H₂O)_0.8n). The name carbohydrate reflects the idea, based on this empirical formula, that these compounds are hydrates of carbon. It is not strictly correct but illustrates an important point about this group of compounds – the relative abundance of hydrogen and oxygen, in proportions similar to those in water, in their molecules. From the discussion above, it will be apparent that carbohydrates are mostly relatively polar molecules, miscible with, or soluble in, water. Carbohydrates in nature include the plant products starch and cellulose and the mammalian storage carbohydrate glycogen (‘animal starch’), as well as various simple sugars, of which glucose is the most important from the point of view of human metabolism. The main source of carbohydrate we eat is the starch in vegetables such as potatoes, rice, and grains.

The chemical definition of a sugar is that its molecules consist of carbon atoms, each bearing one hydroxyl group (–OH), except that one carbon bears a carbonyl group (=O) rather than a hydroxyl. In solution, the molecule exists in equilibrium between a ‘straight-chain’ form and a ring structure, but as the ring structure predominates sugars are usually shown in this form (Figure 1.7). Nevertheless, some of the chemical properties of sugars can only be understood by remembering that the straight-chain form exists. The basic carbohydrate unit is known as a monosaccharide. Monosaccharides may have different numbers of carbon atoms, and the terminology reflects this: thus, a hexose has six carbon atoms in its molecule, a pentose five, and so on. Pentoses and hexoses are the most important in terms of mammalian metabolism. These sugars also have ‘common names’ which often reflect their natural occurrence. The most abundant in our diet and in our bodies are the hexoses glucose (grape sugar, named from the Greek γλυκύς [glykys] sweet), fructose (fruit sugar, from the Latin fructus for fruit), and galactose (derived from lactose, milk sugar; from the Greek γαλακτος [galaktos], milk), and the pentose ribose, a constituent of nucleic acids (the name comes from the related sugar arabinose, named from Gum arabic).

Figure 1.7 Some simple sugars and disaccharides. Glucose and fructose are shown in their ‘ring’ form. Even this representation ignores the true three-dimensional structure, which is ‘chair’ shaped: if the middle part of the glucose ring is imagined flat, the left-hand end slopes down and the right-hand end up. Glucose forms a six-membered ring and is described as a pyranose; fructose forms a five-membered ring and is described as a furanose. In solution the α- and β- forms are in equilibrium with each other and with a smaller amount of the straight-chain form. The orientation of the oxygen on carbon atom 1 becomes fixed when glucose forms links via this carbon to another sugar, as in sucrose; α- and β-links then have quite different properties (e.g. cellulose vs starch or glycogen).

Complex carbohydrates are built up from the monosaccharides by covalent links between sugar molecules. The term disaccharide is used for a molecule composed of two monosaccharides (which may or may not be the same), oligosaccharide for a short chain of sugar units, and polysaccharide for longer chains (>10 units), as found in starch and glycogen. Disaccharides are abundant in the diet, and again their common names often denote their origin: sucrose (table sugar, named from the French, sucre), which contains glucose and fructose (Figure 1.7); maltose (two glucose molecules) from malt; lactose (galactose and glucose) from milk. The bonds between individual sugar units are relatively strong at normal hydrogen ion concentrations, and sucrose (for instance) does not break down when it is boiled, although it is steadily broken down in acidic solutions such as cola drinks; but there are specific enzymes in the intestine (described in Chapter 4) which hydrolyse these bonds to liberate the individual monosaccharides.

Polysaccharides differ from one another in a number of respects: their chain length, and the nature (α- or β-) and position (e.g. ring carbons 1–4, 1–6) of the links between individual sugar units. Cellulose consists mostly of β-1,4 linked glucosyl units; these links give the compound a close-packed structure which is not attacked by mammalian enzymes. In humans, therefore, cellulose largely passes intact through the small intestine where other carbohydrates are digested and absorbed. It is broken down by some bacterial enzymes. Ruminants have complex alimentary tracts in which large quantities of bacteria reside, enabling the host to obtain energy from cellulose, the main constituent of their diet of grass. In humans there is some bacterial digestion in the large intestine (Chapter 4, Box 4.3). Starch and the small amount of glycogen in the diet are readily digested (Chapter 4).

The structure of glycogen is illustrated in Figure 1.8. It is a branched polysaccharide. Most of the links between sugar units are of the α-1,4 variety but after every 9–10 residues there is an α-1,6 link, creating a branch. Branching makes the molecules more soluble, and also creates more ‘ends’ where the enzymes of glycogen synthesis and breakdown operate. Glycogen is stored within cells, not simply free in solution but in organised structures which may be seen as granules on electron microscopy. Each glycogen molecule is synthesised on a protein backbone, or primer, glycogenin. Carbohydrate chains branch out from glycogenin to give a relatively compact molecule called proglycogen. The glycogen molecules that participate in normal cellular metabolism are considerably bigger (Figure 1.8), typically with molecular weights of several million. The enzymes of glycogen metabolism are intimately linked with the glycogen granules.

Figure 1.8 Structure of glycogen. Left-hand side: each circle in the upper diagram represents a glucosyl residue. Most of the links are of the α-1,4 variety. One of the branch points, an α-1,6 link, is enlarged below. Amylopectin, a component of starch, has a similar structure. Amylose, the other component of starch, has a linear α-1,4 structure. Right-hand side: glycogen is built upon a protein backbone, glycogenin. The first layer of glycogen chains forms proglycogen, which is enlarged by addition of further glucosyl residues (by glycogen synthase and a specific branching enzyme, that creates the α-1,6 branch-points), to form macroglycogen. When glycogen is referred to in this book, it is the macroglycogen form that is involved. Source: pictures of proglycogen and macroglycogen taken from Alonso, M. D., Lomako, J., Lomako, W. M., & Whelan, W. J. (1995). FASEB Journal, 9:1126–1137. Copyright 1995 by Federation of American Societies for Experimental Biology (FASEB). Reproduced with permission of FASEB.

The carbohydrates share the property of relatively high polarity. Cellulose is not strictly water soluble because of the tight packing between its chains, but even cellulose can be made to mix with water (as in paper pulp or wallpaper paste). The polysaccharides tend to make ‘pasty’ mixtures with water, whereas the small oligo-, di-, and monosaccharides are completely soluble. These characteristics have important consequences for the metabolism of carbohydrates, some of which are as follows:

1 Glucose and other monosaccharides circulate freely in the blood and interstitial fluid, but their entry into cells is facilitated by specific carrier proteins.

2 Perhaps because of the need for a specific transporter for glucose to cross cell membranes (thus making its entry into cells susceptible to regulation), glucose is an important fuel for many tissues, and an obligatory fuel for some. Carbohydrate cannot be synthesised from the more abundant store of fat within the body. The body must therefore maintain a store of carbohydrate.

3 Because of the water-soluble nature of sugars, this store will be liable to osmotic influences: it cannot, therefore, be in the form of simple sugars or even oligosaccharides, because of the osmotic problem this would cause to the cells. This is overcome by the synthesis of the macromolecule glycogen, so that the osmotic effect is reduced by a factor of many thousand compared with monosaccharides. The synthesis of such a polymer from glucose, and its breakdown, are brought about by enzyme systems which are themselves regulated, thus giving the opportunity for precise control of the availability of glucose.

4 Glycogen in an aqueous environment (as in cells) is highly hydrated; in fact, it is always associated with about three times its own weight of water. Thus, storage of energy in the form of glycogen carries a large weight penalty (discussed further in Chapter 7).