General principles of metabolism
This chapter focuses on the general principles of metabolism. Once the food has been digested and absorbed, the various nutrients are distributed to the tissues via the blood and, having passed through the cell membranes, are exposed to the metabolic machinery of the cell. The aim of this machinery is to release some of the energy contained in the nutrients and convert it into a form that can be used for the various functions of the cell, and to use the rest of the material for the synthesis of substances that the body needs for its growth and activities. To do this, the food materials are subjected to a variety of metabolic processes, each of which involves a well-defined sequence of reactions. Nearly every step is catalyzed by a different enzyme and results in a small but specific chemical change. This field of intermediary metabolism constitutes a major part of biochemistry. Metabolism may be divided into three areas. Catabolism deals with the breakdown of materials with the release of energy. Anabolism covers the processes by which complex substances are built up from simple precursors, and this utilizes much of the energy released during the course of catabolism. Between the clearly defined anabolic and catabolic pathways lies a central area of metabolism in which various simple compounds are interconverted.
Once the food has been digested and absorbed, the various nutrients are distributed to the tissues via the blood and, having passed through the cell membranes, are exposed to the metabolic machinery of the cell. The purpose of this machinery is (1) to release some of the energy contained in the nutrients and convert it into a form that can be used for the various functions of the cell, and (2) to use the rest of the material for the synthesis of substances that the body needs for its growth and activities.
In order to do this the food materials are subjected to a variety of metabolic processes, each of which involves a well-defined sequence of reactions. Nearly every step is catalysed by a different enzyme, and results in a small but specific chemical change. This field of intermediary metabolism constitutes a major part of biochemistry. The main metabolic pathways have by now all been elucidated, and metabolic maps prepared, which show the possible origins and fates of all the major cellular constituents.
Broadly speaking, metabolism may be divided into three areas. (1) Catabolism. This deals with the breakdown of materials with the release of energy. In the process, carbon dioxide and water are produced, but these are essentially by-products since it is the energy liberated during their formation that the body requires, and rarely the carbon dioxide and water themselves. (2) Anabolism covers the processes by which complex substances are built up from simple precursors, and this utilizes much of the energy released during the course of catabolism. (3) Between the clearly defined anabolic and catabolic pathways lies a central area of metabolism in which various simple compounds are interconverted. The pathways are said to be amphibolic since they have a dual function (amphi = both) and provide material which may be used either for synthesis or for breakdown. All the metabolic pathways involve the uptake or release of energy. Energy is required for:
Without the expenditure of energy, membranes and other cell structures would disintegrate and it is only by the constant expenditure of energy that living organisms are able to adapt continually to the prevailing conditions.
The study of energy exchanges is known as thermodynamics, and covers the fields of heat movement and overall energy exchange. The First Law of Thermodynamics is the Law of Conservation of Energy, which states that ‘energy is neither created nor destroyed’, although different forms of energy are often interconvertible. In everyday life it is seen that mechanical forms of energy can be converted into electrical energy by a generator and the kinetic energy of water into electricity by a suitable turbine. Moreover, since electrical energy can be stored in a battery and petrol provides the energy to drive internal combustion engines it is clear that energy can be conserved in the form of chemical compounds. Nevertheless, although many forms of energy are interconvertible, conversion is never quantitative, and a large proportion is always lost as heat.
According to the Second Law of Thermodynamics, any organized collection of matter tends towards a state of maximum randomness or disorder. It is this tendency that determines the direction in which energy will move within a system which is not already in equilibrium. For example, the ordered condition of a gas at high pressure in contact with a gas at low pressure will not persist; gas will flow from the high pressure region to the low pressure region thereby replacing an ordered state by a random one. As explained in Chapter 16, similar considerations govern the direction in which chemical reactions will proceed, the tendency which any given reactants have to form products being expressed by the equilibrium constant (Keq). Reactions occur because the final state is more random than the initial state. This randomness is called entropy, and another way of expressing the Second Law of Thermodynamics is to say that all systems tend towards maximum entropy. Living systems are highly ordered, so that their development, at first sight, appears to be in direct conflict with this law. The localized ordering of living systems is achieved by increasing the randomness of their surroundings since a decrease in entropy (increase in orderliness) can occur provided that it is coupled with the release of energy and the overall ΔG0 is negative. Consequently considerably more energy must always be removed from the environment than is incorporated into the living organism.
Cells consist of about 70% by weight of water, so that all cellular reactions take place in a predominantly aqueous environment. The conditions therefore are quite different from those under which man-made machines operate. Furthermore, living cells can only survive if both the temperature and the pressure are maintained within a narrow range. As in the case of heat engines, when fuel is burnt oxygen is used up and carbon dioxide is produced; but in the body the energy is released in a controlled manner which makes it possible for a large part of the energy to be utilized for the synthesis of the special carrier of free energy, adenosine triphosphate (ATP), from its precursor adenosine diphosphate (ADP). When 1 mole of glucose is oxidized to carbon dioxide and water, 2878 kJ (688 kcal) of energy are released, whereas only 29–38 kJ (7–9 kcal) are required to convert 1 mole of ADP to ATP. These two quantities of energy are altogether disproportionate but by breaking down the glucose in a large number of small steps, the amount of energy released during certain of the reactions is converted to the same order of magnitude as that required for the formation on one high-energy bond (page 211). Even so, only about half of the energy released during the breakdown of foodstuffs is conserved in the form of ATP, the remainder appearing as heat. However, since the body is equipped with efficient temperature-regulating mechanisms, the heat is transferred to the surroundings with no appreciable rise in body temperature.
A second important difference between living organisms and machines is that living systems are open systems. Whereas a closed system is isolated from its surroundings and reactions occurring within it will proceed only until equilibrium has been established, an open one is in constant interaction with its surroundings from which material (oxygen and food) is continually being withdrawn, whilst other substances (carbon dioxide, urea, heat) are being returned to them. Owing to the very sensitive control mechanisms that have been built into living organisms, and without which their existence would be impossible, they exist in a finely balanced steady state in which the intake of energy and materials is matched with the output. This dynamic equilibrium is maintained by controlling the passage of materials both into and out of the system. Thus, while innumerable reactions are occurring all the time, and each is progressing in a manner that will tend to establish equilibrium, equilibrium is never attained, since new substrates are continually entering the system and products are continually being removed from it.