B1.1 Carbohydrates and lipids

Almost every molecule made by living organisms is built on a framework of carbon atoms. The reason lies in how carbon bonds.

Covalent bonds

A covalent bond forms when two atoms share a pair of electrons. A carbon atom has four electrons in its outer shell, so it forms up to four covalent bonds:

• four single bonds, as in methane (CH₄) or in each –CH₂– of a fatty acid chain; with four single bonds the bonds point to the corners of a tetrahedron, so molecules are three-dimensional;
• or a combination of single and double bonds, as in C=C in unsaturated fatty acids and C=O in carboxyl groups (a double bond shares two pairs of electrons).

Carbon bonds with other carbon atoms and with atoms of other non-metals, especially hydrogen, oxygen, nitrogen and phosphorus (and sulfur). Because carbon–carbon bonds are stable, carbon atoms can link into structures of almost any size and shape:

SI prefixes: an international convention

Biologists measure things from the size of molecules to the energy in food stores, so they use the SI (International System of Units). Its units and prefixes are fixed by international agreement, so a measurement means exactly the same to every scientist in every country.

Many biological molecules are macromolecules: very large molecules that are polymers, chains of smaller subunits called monomers.

Condensation builds polymers

Monomers are linked by condensation reactions. Two molecules are joined by a new covalent bond, and a molecule of water is released: an –OH is removed from one molecule and an –H from the other. In cells these reactions are catalysed by enzymes and need an input of energy.

Two α-glucose molecules join by condensation to form the disaccharide maltose: the –OH on carbon 1 of one glucose and the –H of the –OH on carbon 4 of the other form water, and the remaining oxygen links the two rings by a 1,4 glycosidic bond. Repeating this many times builds starch or glycogen. For nucleic acids, see A1.2 Nucleic acids.

Hydrolysis breaks polymers

Hydrolysis (“splitting with water”) is the reverse of condensation. A covalent bond between two monomers is broken and a water molecule is used up. The water molecule is split: its –H is added to one product and its –OH to the other, so each monomer gets back the group it lost. Digestion depends on hydrolysis, catalysed by enzymes:

• polysaccharides + water → monosaccharides (for example amylase hydrolyses starch to maltose, and maltase hydrolyses maltose to glucose);
• polypeptides + water → amino acids (proteases);
• triglycerides + water → fatty acids + glycerol (lipase).

Monosaccharides are single sugar units: the monomers of carbohydrates. They contain carbon, hydrogen and oxygen, typically in the ratio 1 : 2 : 1, so pentoses (five carbons) have the formula C₅H₁₀O₅ and hexoses (six carbons) C₆H₁₂O₆. In water, most pentose and hexose molecules close up into a ring that contains one oxygen atom; the remaining carbons carry –H, –OH or –CH₂OH groups.

Recognizing pentoses and hexoses

To classify a ring diagram, count every carbon atom, including any outside the ring:

• ribose (in RNA) is a pentose with a five-membered ring of four carbons and one oxygen, plus one carbon in a CH₂OH group;
• glucose is a hexose with a six-membered ring of five carbons and one oxygen, plus carbon 6 in a CH₂OH group;
• fructose is also a hexose, although its ring is five-membered: four carbons in the ring and two CH₂OH groups outside it.

α-glucose and β-glucose

Glucose has two ring forms. In both, the ring oxygen lies between carbons 1 and 5, and carbon 6 (CH₂OH) is above the ring. They differ only at carbon 1: in α-glucose the –OH is below the ring; in β-glucose it is above. Rotate the 3D model to see this.

How glucose’s properties suit its uses

Polysaccharides are polymers of monosaccharides. Switch the 3D model to Starch, glycogen and cellulose to compare their structures.

Starch and glycogen: energy stores

Plants store energy as starch, in starch grains in seeds, tubers and many other cells. Animals, and also fungi, store glycogen, mainly in the liver and in muscles. Both are made of α-glucose:

• Amylose (about 20–30% of starch) is an unbranched chain of α-glucose joined by 1,4 glycosidic bonds. The angle of the bonds makes the chain coil into a helix.
• Amylopectin (the rest of starch) has 1,4 chains with 1,6 glycosidic bonds forming branches, roughly every 20–30 glucose units.
• Glycogen is like amylopectin but more highly branched, about every 8–12 units.

They make good energy stores because:

1. Compact: coiling and branching pack many glucose units into a small space.
2. Relatively insoluble: their molecules are very large, so they hardly dissolve and do not draw water into cells by osmosis.
3. Easily built up and broken down: α-glucose can be added to, or removed from, the ends of the chains by condensation and hydrolysis. Branched molecules have many ends, so a store can be mobilized quickly when glucose is needed, for example from muscle glycogen during exercise.

Cellulose: a structural polysaccharide

Cellulose, the main material of plant cell walls, is made of β-glucose linked by 1,4 glycosidic bonds. In β-glucose the –OH groups on carbons 1 and 4 point to opposite sides of the ring, so to bond, each glucose is turned over relative to its neighbour. The alternating orientation produces a straight, unbranched chain.

Straight chains can lie side by side. –OH groups on neighbouring chains form hydrogen bonds, cross-linking many parallel chains into bundles called microfibrils, a few nanometres wide. Microfibrils have a very high tensile strength, which lets cell walls resist the pressure of water entering the cell. Most animals cannot hydrolyse the β-1,4 bonds; herbivores rely on microorganisms in their gut to do it.

A glycoprotein is a protein with one or more short carbohydrate chains (oligosaccharides) covalently attached. In the plasma membrane these chains project from the outer surface of the cell into the extracellular fluid (see B2.1 Membranes and membrane transport).

The sequence and branching of the sugars in these chains varies between cell types, between individuals and between species. Proteins on other cells, such as receptors and antibodies, can bind to particular carbohydrate structures, so the chains act as identity tags. This is cell–cell recognition. For example, the immune system uses cell-surface markers to tell the body’s own cells (self) from foreign or infected cells (non-self).

The ABO blood group antigens

The ABO antigens are carbohydrate chains on glycoproteins (and glycolipids) in the plasma membrane of red blood cells:

• Almost everyone makes the H antigen, which ends in the sugars galactose and fucose.
• People with an A allele make an enzyme that adds an extra sugar, N-acetylgalactosamine, to the H antigen, making the A antigen.
• People with a B allele make a slightly different enzyme that adds galactose instead, making the B antigen.
• People with blood group O have neither working enzyme, so their red blood cells carry only the H antigen. Group AB cells have both A and B antigens.

The plasma of each person contains antibodies against the A or B antigens their own cells lack, so group A people have anti-B antibodies and group O people have both. If a patient receives red blood cells carrying an antigen they do not have, their antibodies recognize the cells as non-self and bind to them, making them clump together (agglutination). This is why blood for transfusion must be matched. (The inheritance of ABO blood groups is in D3.2 Inheritance.)

What makes a lipid

Lipids are a varied group of substances, defined by their solubility: they dissolve readily in non-polar solvents such as hexane or chloroform but are only sparingly soluble in water. Their molecules consist mostly of carbon and hydrogen joined by almost non-polar C–H and C–C bonds, with few polar or charged groups, so they form few hydrogen bonds with water: they are hydrophobic. The main groups are:

• fats and oils (triglycerides), used for energy storage;
• waxes, for example the waterproof cuticle on leaves;
• phospholipids, which form membranes;
• steroids, such as cholesterol and the sex hormones.

Triglycerides

A triglyceride is made from one glycerol molecule and three fatty acids. Glycerol has three –OH groups. A fatty acid has a long hydrocarbon chain with a carboxyl group (–COOH) at one end. Each fatty acid is joined to glycerol by a condensation reaction between its –COOH and one of glycerol’s –OH groups, releasing water and forming an ester bond. Three condensation reactions make one triglyceride and three water molecules. A triglyceride is not a polymer: it is not a chain of repeating monomers.

Phospholipids

A phospholipid is made in the same way, but glycerol is linked to only two fatty acids, by ester bonds; its third –OH is linked by condensation to a phosphate group. In most membrane phospholipids a further small polar group, such as choline, is attached to the phosphate.

Switch the 3D model to Lipids to see a triglyceride and a phospholipid side by side, and step through the second part of the animation above to watch the three condensation reactions.

Fatty acids differ in the length of their hydrocarbon chain (often 14–20 carbons in animals and plants) and in the number of C=C double bonds in it:

• Saturated fatty acids have only single bonds between carbon atoms, so each carbon holds as many hydrogen atoms as it can: the chain is “saturated” with hydrogen.
• Monounsaturated fatty acids have one C=C double bond.
• Polyunsaturated fatty acids have two or more C=C double bonds.

Double bonds and melting point

Saturated chains are straight and pack tightly, so many weak attractions form between neighbouring chains and more energy is needed to separate them: they have high melting points. In most natural unsaturated fatty acids each double bond is cis: the two hydrogen atoms on the C=C are on the same side, which puts a bend in the chain. Bent chains pack loosely, so they melt at lower temperatures. In a trans double bond the hydrogen atoms are on opposite sides and the chain stays nearly straight. Trans fatty acids are uncommon in nature; most in food came from partially hydrogenating plant oils.

Triglycerides rich in unsaturated fatty acids are oils, liquid at 20 °C. Those rich in saturated fatty acids are fats, solid at 20 °C.

Oils in plants, fats in endotherms

An energy store must stay liquid enough to be mobilized. Plants cannot keep their tissues warm, so they store energy as oils, rich in unsaturated fatty acids, which stay liquid even in cold conditions; examples are the oils of sunflower seeds and olives. Endotherms (birds and mammals) keep their body at a constant high temperature, about 37 °C in most mammals and around 40 °C in birds, so they can store fats with more saturated fatty acids, which are soft or liquid at body temperature. Fats like lard and butter are solid at room temperature but not inside the animal.

Adipose tissue is made of cells (adipocytes) that each store a large droplet of triglyceride. In mammals it lies mainly under the skin (subcutaneous fat) and around organs such as the kidneys.

Why triglycerides suit long-term energy storage

• More energy per gram: oxidizing triglyceride releases about 37 kJ g⁻¹, roughly twice the ≈ 17 kJ g⁻¹ of glycogen, because fatty acids contain more C–H bonds and less oxygen.
• Stored without water: triglycerides are hydrophobic, so they coalesce into droplets containing almost no water. Glycogen is hydrophilic and is stored with roughly 3 g of water for every gram. A glycogen store holding the same energy would be several times heavier, a large cost for an animal that must move, and especially for one that flies.
• Inert and insoluble: fat droplets have no osmotic effect and do not react with other molecules in the cell.

Glycogen remains useful as a short-term store: it can be hydrolysed to glucose faster, and glucose can be respired anaerobically, whereas fatty acids can only be respired aerobically. So animals store a little glycogen for rapid use and most of their energy as fat for the long term.

Thermal insulation

Fat conducts heat poorly, so a layer of adipose tissue under the skin reduces heat loss from the body. This matters most for endotherms whose body temperature is far above that of their habitat. Blubber, a thick layer of fat in whales and seals, insulates them in polar seas, where the water is close to 0 °C and conducts heat away far faster than air. The thickness of the fat layer reflects habitat: in hot deserts camels store much of their fat in the hump instead of under all their skin, which makes it easier for them to lose heat.

A phospholipid molecule has two very different regions:

• the phosphate head, which is charged (polar), so it is hydrophilic: it is attracted to water and forms hydrogen bonds with it;
• the two fatty acid tails, which are non-polar hydrocarbon chains, so they are hydrophobic.

A molecule with both a hydrophilic and a hydrophobic region is amphipathic.

When phospholipids are mixed with water they arrange themselves, without any energy input, into a bilayer: two layers of molecules with the hydrophobic tails pointing inwards, towards each other, and the hydrophilic heads facing outwards into the water on each side. This arrangement keeps the tails away from water and the heads in contact with it. The tails in the middle are held together by hydrophobic interactions, and the bilayer tends to close up into continuous sheets, without free edges.

The phospholipid bilayer is the basis of every biological membrane. Its hydrophobic core is a barrier to ions and polar molecules, which is why cells need membrane proteins to move them. Membrane structure and transport are covered in B2.1 Membranes and membrane transport.

Triglycerides are different: they have no hydrophilic head, so they are not amphipathic and cannot form bilayers. Instead they gather into droplets, as in adipose cells.

Recognizing a steroid

Steroids are lipids whose molecules are all built on the same skeleton: four fused rings of carbon atoms, three with six carbons and one with five. Steroids differ in the groups attached to this ring system and in the positions of C=C double bonds. To identify a molecule as a steroid from a diagram, look for the four fused rings, arranged as in the figure. Examples include cholesterol (in animal cell membranes) and the sex hormones testosterone, made mainly in the testes, and oestradiol, a form of oestrogen made mainly in the ovaries.

Passing through the bilayer

A steroid molecule is almost entirely carbon and hydrogen, with only one or two polar –OH or C=O groups, so overall it is non-polar. It can dissolve in the hydrophobic core of the phospholipid bilayer and therefore diffuses straight through membranes, without needing a channel or carrier protein. This is why steroid hormones such as testosterone and oestradiol can leave the cells that make them and enter their target cells. Inside a target cell they bind to receptor proteins in the cytoplasm or nucleus, which then affect which genes are expressed.

Compare this with peptide hormones such as insulin, which are polar or large and cannot cross the bilayer, so they bind to receptors on the outer surface of the plasma membrane.