There are a variety of molecular building blocks that are important in living matter. They can be divided into a range of classes of molecules: proteins (see lectures 3 and 4 of this topic: ‘Protein structures’ and 'Protein folding’), nucleic acids (see Lecture 1 ‘The structure of DNA and RNA’), carbohydrates and lipids. The latter two will be discussed in this lecture.

Carbohydrates and lipids each represent an enormous family of molecules with some common characteristics. However, when it comes to biological purpose, even small and subtle differences in the placement of a single additional group can make a vast difference. This lecture introduces the different key molecules in these classes, and discusses their structures and properties briefly. Slide 1 shows a scanning electron microscopy image of starchy potato, with its growth rings revealed by enzymatic etching.

5.1 Carbohydrates

5.1.1 Simple sugars

Carbohydrates are compounds of only carbon, hydrogen and oxygen. As a class of molecules, they cover both the (small molecule) sugars and the long-chain polysaccharides. They form a major part of the human diet, though with variations in type around the world. The simplest molecules in this class are the monosaccharides, which include the common sugars glucose and fructose. The simplest way of representing such a sugar is in linear form (Slide 2a) known as a Fischer projection, but in practice the molecules exist in ring form (also shown in Slide 2a), which is thermodynamically more stable. This is formed by condensation of the carbonyl group with a hydroxyl group at the far end of the chain to form a so-called acetal. This structure is better able to explain the reactions of simple sugars. However, even this does not really give an adequate view of the structure – such a two-dimensional projection is not the most helpful way of visualizing the structure, and slide 2a shows the so-called Haworth projection, which provides more insight into the three-dimensional structure of the molecule (Slide 2b). In this, the ring is treated as planar, drawn as if perpendicular to the page. The bonds of the various carbon atoms of the ring are drawn perpendicular to this plane.

The numbering of the carbon atoms follows organic chemistry convention in counting from the more oxidized end of the molecule, in this case the carbonyl group. Such a representation indicates that there are in fact two equivalent but distinguishable structures for the ring form. In the so-called Α-form, the hydroxyl group on carbon atom 1 points down in the Haworth projection, whereas in the Β-form, the hydroxyl group points up. All other parts of the molecule are unchanged.

The ring structure of the simple sugars forms the basic building block for larger molecules: oligosaccharides, containing just a few sugar rings, and polysaccharides, with many repeating rings in a chain. The common disaccharides lactose and sucrose are shown in Slide 3. Again, these are built up from the six-membered ring form of the simple sugar. The disaccharides are formed by a condensation reaction, in which the glycosidic bond linking the two sugar rings is formed with the production of water. The glycosidic bond (the covalent bond that joins a carbohydrate molecule to another group) can itself be in an Α- or Β-form, depending on whether the hydroxyl group involved in the bond is in the Α or Β configuration. T P Coultate (see references) offers a useful discussion of simple sugars.

5.1.2 Polysaccharides

These same principles apply when the long chain polysaccharides are formed, but there are clearly many possible variants. Unlike proteins, polysaccharide molecules of a particular type are not all identical. The total chain length (giving rise to the molecule’s relative molar mass), the details of any branching and the precise sequence of sugars along the chain may vary within the same population. This is much more akin to the lack of regularity found in synthetic polymers than in proteins. It should also be noted that some of the important polysaccharide molecules may be derived not from pure sugars but from glucosamines, in which – as their name suggests – amine residues are also present. One example of such a molecule is chitin, a major constituent of arthropod shells.

The familiar polysaccharide starch is actually made up of two closely related biopolymers: linear amylose and highly branched amylopectin. Both (shown in Slide 4) are based on the glucose unit repeated many times. Their total relative molar mass can run into millions of daltons. In most wild species of plant, the ratio of the two components is around 70% amylopectin and 30% amylose, but there are mutants, including those of natural origin, in which amylose is completely absent. These are known as waxy mutants. In the freely jointed chain model of polymer elasticity, the molecular size R, in relation to the basic building block length b, is given by R = b√N, which indicates that for a typical number of repeats (N) of thousands, the molecular size is large, with the mean end-to-end distance being proportional to the square root of the number of repeats (see Lecture 1 ‘The structure of DNA and RNA’). For polysaccharides such as the amylose and amylopectin molecules of starch, the freely jointed model is reasonably good as the bonds have considerable rotational freedom.

Cellulose (Slide 5), the major constituent of plant cell walls and possibly the most abundant organic material on earth, is rather similar to starch. However, the switch from Α 1-4 bonding in the backbone of amylose and amylopectin to Β 1-4 in cellulose means that the molecule adopts a highly extended planar shape that is capable of both intra- and intermolecular hydrogen bonding. The freely jointed chain (see lectures 1 and 2) is not appropriate to model the conformation, and the end-to-end distance will be closer to Nb rather than √Nb. In turn, the nature of this bonding means that whereas starch is readily soluble, particularly in warm water (as used frequently in cooking), cellulose is extremely difficult to dissolve. The paper and textile industries know this to their cost and need to use noxious solvents to break cellulose down.

The extended shape of the molecule and interchain hydrogen bonding is crucial in conferring strength on cellulose assemblies, such as the plant cell wall. This entity is complex, with a subtle packing known as helicoidal, reminiscent of the way in which layers of plywood are stacked with a rotating orientation to ensure good mechanical properties in all directions (Slide 6). When sections of such packing are imaged - for instance by transmission electron microscopy - arcs are seen, as represented by the schematics on the right of the figure.

In passing, it should be noted that the highly aligned packing of cellulose in the layers of the cell wall is liquid crystalline: there is orientational ordering of the molecules but no positional ordering, so the molecules do not sit on anything resembling a lattice. When cellulose molecules are dispersed in solution, liquid crystalline phases will also form, by virtue of the fact that the molecules possess a high aspect ratio – a key factor in facilitating liquid crystalline packing. Many biological molecules and assemblies (notably viruses) possess similarly highly rigid and anisotropic shapes and form liquid crystalline phases in solution. (For further discussion of liquid crystallinity in biology, see Donald et al.)

5.1.3 Polysaccharide derivatives

While cellulose is the structural material of the plant kingdom, for many arthropods the crucial material is chitin. This is not a pure polysaccharide but a modified one, now containing nitrogen: it is a long-chain polymer of N-acetyl glucosamine, a derivative of glucose. As with cellulose, the bonding in the chain is Β 1-4, leading to an extended structure that is capable of forming a strong network of hydrogen bonding leading to a very stiff material. In nature in, for example, insect cuticle, the chitin is embedded in a proteinaceous matrix, leading to a tougher material: pure chitin would be very brittle.

5.1.4 Carbohydrate function

Carbohydrates play a key role in many aspects of cell function, much of it associated with the energetics of life, but also – notably in plants and bacteria – in the structure and strength of an organism. Small sugars play an important part in energy metabolism, whereas some of the polysaccharides act as an energy store in times of plenty, with their subsequent breakdown releasing energy as required. Glucose is a key example and will be used here to illustrate how organisms, including humans, can utilise small sugars.

In many vertebrates, glucose is the main sugar in the blood and consequently the main energy source for living cells. Glucose arises directly from the diet, or is generated by the breakdown of appropriate polysaccharides (glycogen in vertebrates, the disaccharide sucrose in the vascular system of plants or stored starch elsewhere in plants), as discussed in more detail below.

The oxidation of glucose is highly exothermic. In aerobic conditions, when the availability of oxygen is not limited, glucose is completely oxidized to carbon dioxide and water and the maximum amount of energy – 2881 kJ/mol – is given out (Slide 7).

However, in many cases the process (respiration) takes place either in the absence of oxygen (anaerobic respiration) or in limited oxygen. Anaerobic respiration (respiration when the oxygen supply is limited) proceeds via glycoloysis, in which glucose is broken down to pyruvate in a series of stages involving adenosine triphosphate (ATP)(see lectures 1 and 2 in the ‘Biological energy’ topic).

Polysaccharides are also used for energy storage. In plants, the storage occurs in many different parts in the form of starch granules. In the leaf, these are small and turn over every day with a circadian rhythm; in plants such as wheat and maize, the granules are large and form in the heads of the crop where they grow over an extended period; in potatoes, the granules reside underground in the tuber and again mature over a significant timespan. The granules contain two broad classes of starch molecules: the linear molecule amylose and the highly branched molecule amylopectin, packed together in a hierarchical way (Slide 8). These molecules demonstrate the point mentioned earlier about the variability of polysaccharide molecules. Branch points occur essentially randomly, although for a given species one can identify an average frequency and length.

5.2 Structural proteins

5.2.1 Collagen and keratin

Although arthropod cuticle is made of a polysaccharide-derived material, many structural elements, not least in our own bodies, are based on proteins. In this category are keratin (e.g. in our skin and hair) and collagen (a major constituent of muscle, bone and skin). Cellulose and keratin are stiff molecules – conferring good mechanical properties – because they are highly extended and have substantial hydrogen bonding. Crudely speaking, any attempt to stretch such molecules, or their assemblies, requires the distortion of covalent bonds, unlike the case for more coiled polymers, such as those in starch. The structural proteins are likewise hard to deform but tend to rely on their secondary structure to produce the overall stiffness. Both collagen and keratin form superhelical structures, held in place again by hydrogen bonding. In the case of collagen it is a triple helix that forms (Slide 9).

5.2.2 Lipids

Lipids are another hugely important and diverse class of biological molecule. Their role in the cell membrane is discussed elsewhere (see lectures 3, 4 and 5 in the 'Statistical thermodynamics' topic). Lipids that form cell membranes are necessarily amphiphilic, that is they have a hydrophobic core and a hydrophilic tail, this structure being an essential requisite for the bilayer formation of the membrane. They are frequently phospholipids (Slide 10) with the charged and hydrophilic head group being phosphorylated and with a double hydrophilic tail.

However, many other lipids – often known more colloquially as fats – are simply hydrophobic and are therefore insoluble in water. Examples of these are shown in Slide 10. In biology generally, as in our bodies, lipids are often used as a means of energy storage, as well as key components in membranes. They can also act as signalling molecules.

Lipids typically use some form of fatty acid as a major part of the molecule. There are a whole family of fatty acids, which basically consist of a hydrocarbon chain attached to the –COOH acid end group. The length of the hydrocarbon chain determines the type of fatty acid, and there may be one or more double (unsaturated) bonds present (Slide 11). The length of the chain is the dominant factor – along with the proportion of carbon–carbon bonds that are single bonds – which affects the melting point of the chain, with shorter chains having a lower melting point and therefore yielding a more fluid substance. Additionally, the higher the degree of unsaturation, the lower the melting point, because (as Slide 9 shows) unsaturation leads to kinks in the chain, which reduces the ability of chains to pack closely. In many situations, mixtures of fats are present to control the fluidity of the material. This is most important for organisms that cannot control their own temperature but simply reflect that of their environment. For some plants, for instance, the lipid make-up of membranes can be changed to alter their transition temperature (between fluid and solid) by as much as 20 oC.

In practice, the fatty acids are usually present as part of molecules known as triglycerides, derived from glycerol, in which different fatty acids are attached to the three hydroxyl groups of glycerol (Slide 12). These triglycerides – neutral lipids – are a major form in which fatty acids are transported between tissues. They are also a fundamental source of energy storage for organisms and, of course, a major source of calories for humans (e.g. think of cocoa butter in chocolate, the properties of which are derived from the balance of triglycerides present; the particular mixture depends on the country of origin).