FOOD, glorious food, where would we be without it? A balanced diet supplies us with a mixture of energy-rich fats, proteins and carbohydrates. Chewing food physically breaks it up into pieces and chemical processes dismantle it further into smaller fats, sugars and amino acids. These molecules are absorbed into the bloodstream and transported to cells, where they undergo a series of chemical reactions that are collectively called metabolism. Metabolic processes are divided into two groups: catabolic processes that break up large molecules into small sub-units, often releasing energy, and anabolic processes in which small units are linked together to form larger molecules, often requiring an input of energy.
A constant demand for energy is a key requirement of every living animal, plant, fungus or bacterium. For all life on Earth, the ultimate source of energy is the Sun. Plants are able to harness this solar power directly (through a process called photosynthesis) and use it for anabolic purposes such as building their structures, maintaining an energy reserve for night time, or storage as starch in seeds or tubers (potatoes, for example), enabling a new plant to start growing without having to photosynthesise immediately.
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Losing electrons
THE SHAPE of an organism is, to a large extent, determined by its need to acquire energy. For example, leaves provide plants with a large surface area to photosynthesise, herbivores such as cows typically have vast stomachs, or rumens, in which they can ferment large quantities of grass, and carnivores tend to be small and fast so that they can chase moving prey. By eating vegetation, herbivores make use of the solar energy stored in plants. Carnivores also indirectly tap into the Sunās power by eating other animals.
A regular energy supply is the only way that living organisms can survive in a Universe where the second law of thermodynamics holds sway. According to this law, all physical and chemical systems tend to become more disorganised. As randomness increases, a system is said to be increasing its level of entropy (see Inside Science No. 75).
In an organism, the majority of chemical reactions occur within cells. Each cell in our body can be likened to a complex chemical factory equipped to perform hundreds of reactions. In a typical liver cell, for example, more than 600 separate reactions occur routinely. In order for cells to perform chemical reactions at a rate that is fast enough to sustain life, the reactions need to be catalysed. This job is done by biological catalysts called enzymes. Metabolic processes consist of sequences of individual steps, where the product of one reaction becomes the substrate (reactant) for the next. Consequently, enzymes need to be grouped into organised systems, allowing molecules to be processed step by step, as if they were on a factory conveyor belt.
Cells contain various tiny āorgansā, or organelles, which perform specific tasks. Mitochondria, present in most living cells, are effectively small packages of enzymes needed to produce energy from food. The enzymes are either found within the central space (or matrix) of the mitochondrion, or are bound to its highly folded inner membranes. Here the cell produces most of its energy by the chemical process of oxidation. Biologists call the whole energy producing procedure cell respiration.
Oxidation always involves the loss of electrons from molecules, atoms or ions. This is achieved either by adding oxygen or by removing hydrogen. This can be simply summarised as:
X ā X+ + 1 electronā ā X
Nutrients that have molecules with a high ratio of hydrogen to oxygen are more likely to lose electrons and release energy. They make excellent energy sources. A fat such as stearic acid (C17H35COOH), for example, has a hydrogen to oxygen (H:O) ratio of 18:1. Oxidising one gram of stearic acid can release some 38 kilojoules of energy. Glucose (C6H12O6), with a 2:1 H:O ratio, is already partially oxidised but is capable of releasing 17 kilojoules per gram.
Reduction is the opposite of oxidation. Molecules are said to have been reduced when they increase the number of electrons they contain, often by the addition of hydrogen or loss of oxygen:
X+ + 1 electronā
Whereas oxidation releases energy, reduction is driven by an input of energy. An example of reduction in biological systems is the formation of large, complex molecules from smaller ones, as happens in growth. This process requires energy, which is supplied by the oxidation of other molecules.
One of the primary sources of energy is glucose, the basic building block of starch and many sugars in our diet. Its oxidation in cell respiration can be subdivided into three phases: glycolysis, the Krebs cycle and the system of electron transport.
Pathways of power
Cycles and chains
THE FIRST stage, glycolysis, involves the breakdown of glucoseās six-carbon ring into two three-carbon molecules called pyruvate. To start the ball rolling, energy must be added to glucose to make it more reactive. This is achieved by adding two high-energy phosphate groups donated from two molecules of adenosine triphosphate (ATP). ATP is the universal carrier of energy in living cells. It plays a key role in linking metabolism to energy-requiring activities such as growth and muscle contraction. Once the high-energy phosphates have been added, the activated glucose molecule is able to split into two smaller compounds. These undergo a series of oxidation reactions -losing hydrogen and supplying energy for the formation of four molecules of ATP. The end-product is a pair of three-carbon pyruvate molecules and a net gain of two ATP molecules.
In most organisms, the fate of pyruvate depends on whether or not oxygen is present. Producing energy in the absence of oxygen is called anaerobic respiration. If oxygen is not available then no more energy can be extracted and there is a net gain of only two ATPs and four hydrogen atoms per glucose molecule. And in order for glycolysis to continue producing energy in the absence of oxygen, the hydrogens must be mopped up, otherwise they would bring the reaction grinding to a halt. The single-celled organism called yeast does this by combining each hydrogen atom with one molecule of pyruvate, forming alcohol (ethanol) and carbon dioxide. This reaction, called fermentation, is exploited by the brewing industry. Another kind of fermentation occurs in the absence of oxygen in animals: this time each pyruvate accepts a pair of hydrogen ions and forms a compound similar to alcohol called lactate. Tissues can tolerate large amounts of lactate before they start to malfunction, but when the lactate concentration becomes too high, muscles develop cramp-like pains.
Forming ethanol or lactate in anaerobic respiration is a highly inefficient way of using glucose. If a molecule of glucose is completely oxidised it releases 2880 kilojoules of energy. Each ATP molecule yields 30.6 kilojoules, but only two are gained during glycolysis (four are made and two are used up), so a total of 61.2 kilojoules made available to the organism. This means that anaerobic respiration has only 2.1 per cent efficiency.
Removing excess hydrogen ions by forming lactate rather than ethanol has the advantage that as soon as a supply of oxygen resumes, the lactate can re-enter the metabolic pathway and be further oxidised, releasing the energy it contains.
If oxygen is present, much more energy can be yielded. This is called aerobic respiration. The pyruvate enters a further complex pathway of chemical reactions, and after many steps the hydrogen ions eventually combine with oxygen forming water. Even though oxygen is only required at the very end of the process, without it there is no way of mopping up electrons and the process comes to a standstill.
Cell respiration continues if oxygen is present with the transportation of each pyruvate molecule into a mitochondrion, where it is converted into a two-carbon acetyl molecule, releasing a pair of hydrogen atoms and carbon dioxide. The acetyl molecule can then enter a cycle of chemical reactions called the Krebs cycle, named after its discoverer, the German-born Hans Krebs. This circular pathway of reactions is also known as the tricarboxylic acid (TCA) cycle or the citric acid cycle, after the chemical intermediates that are produced along the way. The Krebs cycle transforms each acetyl group into two carbon dioxide molecules, four pairs of hydrogen atoms and provides energy to build two more ATP molecules. Carbohydrate, fat and some amino acids are oxidised in the Krehs cycle, each plugging into different points in the circle of reactions. Enzymes required for this process are arranged in an orderly sequence within the mitochondrion.
Although the glucose molecule is completely oxidised by this stage, only four ATP molecules have been released in total. The bulk of the energy is generated when the 24 hydrogen atoms produced during the oxidation of glucose offload their electrons into the electron transport system.
This is the final sequence of reactions and involves a series of hydrogen and electron carriers known as co-enzymes. In the first step the hydrogen atoms are passed from the co-enzyme nicotine adenine dinucleotide (NAD), to a second called flavin adenine dinucleotide (FAD). At this point each hydrogen atom passing through the system divides into an electron and a hydrogen ion (a proton). The electrons continue through the rest of the electron transport chain of co-enzymes. The protons rejoin the electrons once they have passed through the chain and combine with oxygen to produce water. The step-by-step transfer of electrons through the system allows protons to be pumped in the opposite direction, out of the inner matrix and across the inner mitochondrial membrane. A large concentration of protons therefore builds up between the inner and outer mitochondrial membranes, forming a āmembrane potentialā (see Inside Science No. 47). This potential is released as the protons flow back into the mitochondrial matrix and energy in the form of ATP is produced.
A total of 38 ATP molecules have now been formed by the oxidation of each glucose molecule, representing a release of 1162.8 kilojoules, 40 per cent of the total energy locked up in the molecule. Energy produced from metabolism enables an animal to perform all the anabolic processes required to grow, repair damaged and worn-out parts and produce substances for secretion. Energy is also needed to transport substances. Cell membranes are packed with pumps that move ions and molecules such as glucose from one side to the other against a concentration gradient, a process called active transport. Nerve cells consume energy maintaining the concentration gradients of ions in their axons.
Muscles need energy to power their contraction. At rest, muscles use fatty acids, broken down from fat, as an energy source. During exercise they break down stores of glycogen into glucose which they take up from the bloodstream. Initially, blood glucose may rise as the liver breaks down vast amounts of glycogen, but after a few minutes of strenuous exercise the glucose level will fall.
Metabolic demand
Maintain status quo
SOME energy is deliberately used solely to produce heat. In a tissue called brown fat the electron transport system is said to be āuncoupledā. This means that while electrons are free to pass along the series of carriers, no ATP molecules are generated, only energy in the form of heat.
Altogether, animals are quite inefficient at using energy and on average, 55 per cent of all food energy is lost as heat. The amount of heat being released can be used as a gauge of the rate of the chemical reactions going on inside the body. This is called the metabolic rate of an organism.
Many factors influence metabolic rate. It tends to decrease with age, and males tend to have higher rates than females. Fasting and sleeping cause it to decrease, and rates increase by as much as 15 per cent after a meal when food is being broken down in the gut, absorbed into the bloodstream and utilised in cells. Exercise, anxiety and stress all increase metabolic rate. These conditions lead to higher levels of the hormone adrenaline, which speeds up the rate at which cells can perform reactions. Also, muscles tend to be held in permanent tension during times of stress. This requires energy and so increases the amount of heat produced in the body.
Biologists have developed the concept of basal metabolic rate (BMR) to compare individuals accurately. This is a measure of the overall rate of chemical reactions in the subjectās body at least eight hours after a meal, and while they are in a resting state and at room temperature.
Thyroid hormones, which are produced by the thyroid gland in the neck, play an important role in controlling basal metabolic rate. The gland secretes two different molecules ā thyroxine (90 per cent) and triiodothyronine (10 per cent). Both molecules stimulate the production of proteins, including enzymes, and so increase cellular chemical activity. They also stimulate the building of new mitochondria in cells.
When the thyroid gland secretes maximal quantities of thyroid hormone, the metabolic rate doubles compared with the average rate. A total loss of thyroid secretion reduces the metabolic rate by a half. Studies of the metabolic rates of people living at different latitudes have shown that rates are between 10 and 20 per cent lower in tropical regions compared with arctic regions. This difference is caused largely by adaptive changes in the activity of the thyroid gland, with increased secretion in cold climates (generating more body heat) and decreased secretion in hot climates.
While hormones may play an important role in stimulating metabolism, it is also regulated directly at the reaction level in cells. The enzymatic reactions are influenced by the relative concentration of their substrates and products. If the substrate is in short supply then the rate will slow down. However, the rate will also decrease if reaction products build up. This is an example of negative feedback. Two principal mechanisms are at work. Firstly, most biochemical reactions are reversible, and can proceed in either direction depending on the concentration of substrate or product. If product accumulates, the equilibrium changes, causing the reaction to slow down or even to go into reverse. Secondly, some enzymes are actively inhibited by their own reaction products or those produced further along the metabolic pathway. So if the concentration of the product increases it may prevent enzymes from catalysing an earlier step of the process.
Energy balance
Food for thought
BOTH these types of negative feedback actively regulate the rate of ATP production. As we have already seen, the availability of oxygen also determines metabolic rate. A lack of oxygen prevents the last step in the electron transport system from being completed, causing an accumulation of products up to that point and negative feedback. The only way to remedy this is to convert pyruvate into lactate or ethanol, āshort-circuitingā this pathway. If, on the other hand, plenty of ATP molecules are available and are not being used up very quickly, then the ATP itself actively inhibits three enzymes (hexokinase, phosphofructokinase and pyruvate kinase) that catalyse different stages in glycolysis. This prevents any further ATP molecules being formed from glycolysis.
According to the first law of thermodynamics, which states that energy is conserved, all the energy contained in food consumed by an organism must be accounted for by growth, activity, heat, storage or excreta. It should thus be possible to measure all the energy consumed by an animal and see how it is utilised.
Animals do not store heat for more than a few hours. If you can measure the heat released from an animal over 24 hours or longer, it is generally safe to assume that the quantity of heat lost from the animal is equal to the quantity produced by all its chemical reactions during this period. Heat is lost through radiation, conduction and convection from the body surface and by the evaporation of water from skin and lungs. Measuring this heat loss gives an indication of the overall metabolic rate.
Animals must balance their expenditure of energy with their energy intake. To maintain a stable weight during adult life, intake and expenditure should differ by less than 0.01 per cent. Any persistent excess of intake will lead to an accumulation of fat stores, resulting in obesity. And a deficiency will lead to starvation and wasting.
There are obviously times in life, such as at pregnancy, in childhood and in adolescence, when the aim is to gain weight. For this to occur the intake of energy must exceed the immediate need for keeping the body alive in order to supply the energy that is needed for growth. Mothers who are breast-feeding a baby also need to have enough energy to supply all the childās requirements through their milk.
Much of our daily energy requirement is to maintain the function of our brain. Even during fasting, the brainās energy requirement is estimated to account for between 70 and 80 per cent of all glucose used. That certainly is food for thought.
1: ATP ā The universal carrier of free energy
ADENOSINE triphosphate (ATP) is a nucleotide consisting of an adenine base, a five-carbon sugar called ribose and a string of three phosphate units. Energy is released when each of the outer two phosphate groups is removed. The freey energy liberated is used to drive reactions that require an input of free energy, such as protein synthesis or muscle contraction.
While ATP serves as the principal immediate donor of free energy, it is not used to store energy. On average, an ATP molecule only lasts for a minute. Once it has been broken into ADP and a phosphate group these are ready to be reassembled and supply energy once again. Efficient recycling is vital as a grand total of 40 kilograms of ATP is used each day in the average resting adult man, and during intense exercise ATP can be used at a rate of up to 0.5 kilograms per minute.
2: Calorimetry ā the measurement of energy
A METHOD called direct calorimetry allows us to measure the total amount of heat lost from the body. The subject sits in a highly insulated container and the heat released from her body warms the air. Various methods are used to measure this warming. Heat loss due to evaporation is calculated by measuring the difference in the humidity of air entering and leaving the chamber.
Such chambers are expensive to build and difficult to run. However, there is an alternative method, known as indirect calorimetry. This makes use of the fact that the main nutrients supplying energy are carbohydrates, fats and proteins. To release their energy they are oxidised, which consumes oxygen. In an average diet, which consumes oxygen. In an average diet, when 1 litre of oxygen is used 20 kilojoules of energy are released. So the metabolic rate can be calculated by accurately measuring the rate at which the body is using oxygen.
A more recent approach has been developed which involves giving the subject small quantities of water containing the isotopes hydrogen-2 (deuterium) and oxygen-18 and measuring the rate at which they are lost from the body. Hydrogen-2 will only be lost in water, whereas oxygen-18 will leave the body in water and in carbon dioxide. Without having to be confined to a chamber, the personās overall metabolic rate can then be estimated by calculating how much of the oxygen-18 loss can be attributed to the production of carbon dioxide, by comparing it with hydrogen-2 loss.
To devise appropriate diets, it is important to know exactly how much energy is contained in different foods. This can easily be measured by placing a small sample inside a bomb calorimeter, which is then filled with pressurised oxygen. An electric current ignites the sample and the amount of energy released as heat is recorded.
This procedure measures the total amount of energy contained in a sample. In reality, not all molecules can be digested by an organism, and are therefore not available for oxidation. For example, it is often said that there is more energy in a breakfast cereal box than in the cereal itself. This may be true, but little of the energy in the cardboard box is actually available to us because we are unable to dismantle the cellulose molecules.
To make a full assessment of how much of the energy in food is used by an animal one also needs to measure what is lost in urine and faeces. This can be done by collecting them, drying a sample of each and then oxidising the samples, again using a bomb calorimeter.