Molecular Biology of the Cell - Volume 1 - Alberts B., Bray D., Lewis J., Raff M., Roberts K., Watson J. 1994

Introduction to Cell Biology
Small Molecules, Energy, and Biosynthesis
Biological Order and Energy

Cells must obey the laws of physics and chemistry. The principles of mechanics and the law of conservation and transformation of energy apply to a Cell just as they do to a steam engine. However, we must acknowledge that cells possess A number of features that seem puzzling at first glance and might appear to place them in a special category. Everyday experience shows that anything left to itself eventually falls into a state of disorder: buildings crumble, dead organisms decay, and so on. This general tendency is expressed in The Second Law of Thermodynamics, which states that in any isolated system the degree of disorder can only increase.

What is puzzling is that living systems are highly ordered at all Levels of Organization. This order is strikingly apparent in large structures, such as a butterfly's wing or an octopus's eye, in subcellular formations, such as Mitochondria or flagella, and in the shape and arrangement of their constituent molecules. A vast number of atoms are assembled into exceptionally precise structures, yet ultimately all of them were extracted from an environment where they existed in an extremely disorganized state. Even non-dividing cells require a continuous maintenance of order to survive. Because all organized cellular structures are prone to disruption, systems are needed to repair them. How does this fit within the framework of thermodynamics? As we will see shortly, the answer lies in the fact that The Cell constantly releases heat into its environment and, therefore, from the standpoint of thermodynamic laws, it is not an isolated system.

2.2.1. The orderliness of biological systems is driven by the cellular release of thermal energy [7]

Some Principles of Thermodynamics are easier to grasp if we consider the cell and its immediate surroundings as a closed box situated in a uniform sea of matter that constitutes the rest of the universe (Fig. 2-11). To grow and sustain its existence, the cell must constantly maintain order within the box. However, as already mentioned, the second law of thermodynamics dictates that the orderliness of a closed system must always decrease. It follows that any increase in order inside the box must always be more than compensated for by an even greater rise in the disorder of the rest of the universe. Although no exchange of molecules takes place between the box and its environment, they can exchange heat—which is the quantitative manifestation of the relationship between heat and order. Heat represents the energy of chaotic molecular motion, i.e., energy in its most disordered form. By releasing heat into space, the cell increases the vigor of molecular motion, thereby raising the randomness, or disorder, of that motion.

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Fig. 2-11. A simple thermodynamic analysis of a living cell can be approached as follows: the cell and its immediate surroundings are assumed to be enclosed in a sealed box, where they can exchange heat with the rest of the universe while remaining impermeable to molecules. The top diagram shows the molecules of the cell and the rest of the universe in a relatively disordered state. The lower diagram shows heat being released from The Cell as a result of a reaction that has led to the ordering of the molecules contained within the cell. The increase in random motion (including bond deformations) of the molecules in the rest of the universe creates a degree of disorder that more than compensates for the increase in order within the cell, which is consistent with the Laws of Thermodynamics for spontaneous processes. Thus, the release of heat by the cell into its surroundings enables it to generate a higher degree of internal order. At the same time, the universe as a whole becomes more disordered.

The existence of a quantitative relationship between heat and order, discovered in the late 19th century, in principle enables us to calculate The amount of heat a cell must release to compensate for a specific degree of internal order (such as the assembly of Proteins from Amino Acids), provided that the overall process increases the disorder of the universe as a whole. This relationship can be derived by examining how molecular motion changes when a specific quantity of thermal energy flows from a hot body to a cold one. There is no need to present a detailed calculation of such a process here; we need only note that Chemical Reactions accompanied by the release of heat must be closely coupled at THE MOLECULAR LEVEL with processes that lead to order. Such interconnected reactions are known as coupled reactions, and we will examine them later. The intrinsic link between heat generation and the increase in order is precisely what distinguishes cellular METABOLISM from the wasteful process of fuel combustion.

Fig. 2-11 illustrates in a very schematic way how these coupled reactions release thermal energy, which increases the disorder of the extracellular medium and thereby compensates for the increase in intracellular order brought about by these reactions. The increase in the universe's disorder is precisely the mechanism that allows the progression of coupled reactions to drive up the level of order within the cell.

Energy can neither be created nor destroyed during chemical reactions; therefore, the continuous loss of heat by the cell, which drives biological order, requires a continuous input of energy into the cell. This energy must exist in a form other than heat. For plants, the primary source of energy is solar electromagnetic radiation, whereas animals utilize the energy of covalent bonds in organic molecules obtained from their food. However, since these organic nutrients are themselves produced by photosynthetic organisms, such as green plants, the ultimate primary source of radiation for both types of organisms is the Sun.

2.2.2. Photosynthetic organisms use sunlight to synthesize Organic compounds [8]

The utilization of solar energy by the living world (the biosphere) occurs through Photosynthesis, carried out by photosynthetic organisms—plants and Bacteria. During photosynthesis, electromagnetic energy is converted into chemical bond energy. Simultaneously, a fraction of the sunlight's energy is dissipated as heat, and it is precisely the release of this heat into the surroundings that increases the disorder of the universe, which serves as the driving force of the photosynthetic process.

Fig. 2-12. Two Stages of Photosynthesis in green plants.

Photosynthetic reactions are described in detail in Chapter 7; broadly speaking, they take place in two distinct phases. In The first phase (light reactions), light quanta excite an electron in a pigment molecule to a higher energy state; subsequently, as it returns to a lower energy level, it releases the energy required to synthesize molecules such as ATP and NADPH. In the second phase (dark reactions), ATP and NADPH are used to drive a series of carbon-fixation reactions in which sugar molecules are produced from atmospheric carbon dioxide (Fig. 2-12).

The overall net result of photosynthesis (in the case of green plants) can be written as the equation

Energy + CO₂ + H₂O + Sugar + O₂,

which is the reverse of the equation for the oxidative breakdown of sugar. Behind this simple expression lies the complex Nature of the dark reactions, which involve numerous interconnected partial reactions. Moreover, while initial CO₂ fixation leads to The formation of sugars, subsequent metabolic reactions rapidly convert these sugars into other small or large molecules essential to The plant cell.

2.2.3. Chemical Energy is transferred from plants to animals

Animals and other non-Photosynthetic organisms are incapable of directly utilizing solar energy; therefore, they must subsist on energy acquired "second-hand"—by eating plants—or even "third-hand"—by preying on other animals. The organic molecules synthesized by plant cells provide plant-eating organisms with both structural building blocks and a reserve of "fuel." All types of plant molecules can serve this purpose, including sugars, proteins, Polysaccharides, Lipids, and many others.

Not all Interactions Between Plants and animals are so one-directional. Plants, animals, and microorganisms have coexisted on our planet for so long that many have become an essential part of the environment for other organisms. Oxygen released during photosynthesis is consumed by nearly all organisms to oxidize organic molecules; a portion of the CO₂ molecules fixed today into larger organic molecules via photosynthesis in green leaves was released into the atmosphere just yesterday through animal Respiration. Thus, carbon utilization is a cyclical process that encompasses the entire biosphere and establishes connections between individual organisms (Fig. 2-13). Similarly, atoms of nitrogen, phosphorus, and sulfur can pass from one biological molecule to another in a series of analogous cycles.

Fig. 2-13. The carbon cycle. Individual carbon atoms are incorporated into the organic molecules of living nature through the photosynthetic activity of plants, bacteria, and marine Algae. These atoms enter the cells of animals and microorganisms, as well as the organic compounds of soils and oceans, via cyclical pathways. When organic molecules are oxidized by cells or burned by humans as fossil fuels, CO₂ is returned to the atmosphere.

2.2.4. Cells derive energy from The oxidation of biological molecules [9]

Carbon and hydrogen atoms within a cell are far from being in their most stable state. Because the Earth's atmosphere contains vast amounts of oxygen, the energetically most stable form of carbon is CO₂, and that of hydrogen is H₂O. Consequently, a cell can extract energy from protein or glucose molecules by creating conditions under which the carbon and hydrogen atoms of these molecules combine with oxygen to form CO₂ and H₂O, respectively. However, the oxidation of molecules within a cell does not occur in a single step, unlike combustion, for instance. Molecules must pass through A large number of reactions, of which only very few involve the direct addition of oxygen. To examine all these reactions and understand the driving forces behind them, we must first develop a clear concept of oxidation.

Oxidation, in the sense described above, is not restricted merely to The addition of an oxygen atom; rather, the term is more general and applies to any reaction in which electrons are transferred from one atom to another. In this sense, the removal of electrons can be called oxidation, and the addition of electrons—reduction (the reverse of oxidation). For example, Fe²⁺ is oxidized when it loses an electron, turning into Fe³⁺, whereas a chlorine atom is reduced when it gains an electron and becomes Cl^-. The same terminology is used when referring merely to the partial displacement of electrons in atoms linked by a covalent bond. For instance, when a carbon atom forms a covalent bond with an electronegative atom such as oxygen, chlorine, or sulfur, it effectively yields a portion of its electron density to them, acquiring a partial positive charge, and can be considered oxidized. Conversely, in a C–H bond, the electrons are more strongly shifted toward the carbon atom, allowing us to consider it reduced (Fig. 2-14).

During the "combustion" of nutrients within a cell, the carbon and hydrogen atoms of organic molecules (which exist in a relatively electron-rich, or reduced, state) are converted into СО₂ and Н₂О, in which they surrender their electrons to oxygen and thus become heavily oxidized. The transfer of electrons from carbon and hydrogen to oxygen allows all these atoms to reach their most stable state, making the process energetically favorable.

Fig. 2-14. A methane carbon atom is converted into carbon dioxide through the successive removal of hydrogen atoms. At each step, electrons are shifted further away from the carbon atom as it transitions to a more stable energy state (in other words, becomes increasingly oxidized).

2.2.5. The breakdown of organic molecules proceeds via a series of sequential enzymatic reactions [10]

Although СО₂ is the energetically most favorable form for carbon and Н₂О for hydrogen, a living Organism does not simply go up in smoke for the same reason that a book in your hand does not burst into flames: both the organism and the book represent metastable energy states of matter (Fig. 2-15) that require activation energy to transition into a more stable form. In the case of the book, this activation energy can be supplied by a lit match. For a living cell, the same ultimate result is achieved through a much less radical and destructive method. Highly specific protein catalysts, or Enzymes, bind to biological molecules in a way that lowers the activation energy for the specific reactions those molecules can undergo. By selectively reducing the activation energy of a particular sequence of reactions (a metabolic pathway), enzymes determine which of several alternative possibilities will be realized (Fig. 2-16). It is precisely in this manner that various cellular molecules are channeled along specific reaction pathways, which ultimately dictates the Chemistry of the cell.

The flourishing of various life forms can be largely attributed to the remarkable capacity of cells to produce a vast array of specific enzymes. Each enzyme is a protein with a unique three-dimensional Structure (conformation) that forms an Active Site, where a specific set of molecules (substrates) binds to the enzyme's surface. The binding of a substrate to an enzyme often increases The rate of one of the many chemical reactions the substrate can undergo by a factor of 10¹⁴. Like all other catalysts, enzyme molecules remain entirely unchanged upon completion of the catalytic process and can therefore perform their Functions repeatedly.

Fig. 2-15. Diagram illustrating THE PRINCIPLE OF activation energy. Compound X can reach a lower, energetically favorable state by converting into compound Y. However, this transition will not occur until X acquires sufficient activation energy to enter the reaction.

Fig. 2-16. The "rocking box model," illustrating how enzymes guide molecules into the required metabolic pathways. In this model, the colored ball (compound X) represents a potential substrate for an enzymatic reaction; the ball bounces up and down due to continuous bombardment by colliding Water molecules. The four walls of the box represent the activation energy (energy barrier) for four different energetically favorable chemical reactions. In the left box, none of these reactions takes place because the energy imparted to the ball by collisions is insufficient to overcome any of the energy barriers. In the right box, Enzymatic Catalysis lowers the activation energy solely for reaction 1, making this reaction (The conversion of compound X into compound Y) possible with the available amount of energy.

2.2.6. A fraction of The energy released in oxidation reactions is channeled into the formation of ATP [11]

Cells derive their required energy from the "combustion" of glucose only because they break it down through highly intricate and tightly controlled processes. Synthetic, or anabolic, chemical reactions that sustain the orderliness of biological systems are closely coupled with degradative reactions (catabolic reactions) that supply energy. The fundamental distinction between coupled and uncoupled catabolic reactions is well illustrated by a mechanical analogy. In Fig. 2-17, an energetically favorable chemical reaction is represented by boulders tumbling down a cliff. The kinetic energy of the falling boulders is normally converted entirely into heat upon impact with the ground (Fig. 2-17, A). With a clever setup, however, a portion of that kinetic energy can be harnessed to drive a paddle wheel that hoists a bucket of water (Fig. 2-17, B). As seen in the figure, the boulders reach the ground only by turning the wheel. Consequently, the spontaneous reaction—the falling boulder—is directly coupled to the non-spontaneous reaction—lifting the water bucket. Because some of the energy is now consumed to perform work (B), the boulders hit the ground at a lower velocity than in case A, and consequently, less energy is lost as heat.

Fig. 2-17. Mechanical model illustrating the principle of coupled chemical reactions. A. A spontaneous reaction serves as an analogue for the direct oxidation of glucose to СО₂ and Н₂О, accompanied by the release of heat alone. B. The same reaction is coupled to a secondary reaction; this second reaction serves as an analogue for ATP synthesis. The diverse forms of energy generated in case B can be utilized to drive other cellular processes, much like the setup shown in figure C. ATP represents the cell's most versatile form of energy storage.

Enzymes play the exact same role in the cell as the paddle wheel in our example, coupling the spontaneous oxidation of nutrients to reactions that synthesize the nucleotide triphosphate ATP. The energy stored in a water bucket hoisted to a certain height (Fig. 2-17) can be expended in small increments to power A wide variety of hydraulic machines (Fig. 2-17, C); similarly, the energy accumulated in ATP—the universal energy currency—can be harnessed to drive the multitude of diverse chemical reactions essential to the cell.

2.2.7. ATP Hydrolysis maintains cellular order [12]

How does ATP function as a chemical energy carrier? Under standard cytoplasmic conditions, the hydrolysis of ATP with the release of inorganic phosphate (Р_і) occurs very readily and is accompanied by the liberation of a large amount of biologically useful energy (Section 2.4.1). A chemical group attached to the ATP molecule by such a reactive bond is readily transferred to another molecule, allowing us to view the terminal phosphate of ATP as being in an activated state. The bonds cleaved in such hydrolysis reactions are sometimes referred to as high-energy bonds. Crucially, the hydrolysis In aqueous solutions yields two molecules with significantly lower energy (ADP and PI); the covalent bonds themselves possess no special intrinsic properties.

Other chemical reactions can proceed at the expense of energy released during ATP hydrolysis, provided they are coupled to this process in some manner. Among the hundreds of reactions driven by ATP hydrolysis, notable Examples include the synthesis of biological molecules, active Transport Across Cell Membranes, and processes responsible for generating mechanical cellular forces and motility. These Three types of processes play a decisive role in maintaining the orderliness of biological systems. Macromolecules produced in biosynthetic reactions carry information, catalyze specific reactions, and assemble into exceptionally ordered structures both within the cell and in the extracellular space. Membrane-bound pumps maintain the specific COMPOSITION OF THE intracellular environment and facilitate the transmission of intra- and intercellular signals. Finally, the presence of mechanical forces and motility enables the self-ORGANIZATION OF THE Cytoplasm, while also allowing cells to migrate and aggregate to form specialized Tissues.

Conclusion

Living cells are remarkably ordered, and maintaining this order is essential for their growth and survival. From a thermodynamic standpoint, this is only possible through a continuous influx of energy, part of which is dissipated by cells into the environment as heat. Generally speaking, the primary source of energy is solar electromagnetic radiation; in photosynthetic organisms, such as green plants, it drives the formation of organic molecules. Animals obtain energy by capturing these organic molecules and oxidizing them through a series of enzyme-catalyzed reactions coupled to the synthesis of ATP. ATP serves as the universal energy currency for all cells, and the hydrolysis of this compound, coupled with other reactions, drives numerous energetically unfavorable processes, thereby ensuring the Creation of biological order.