Human Metabolism. Keith N. Frayn

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.