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
Chemical Components of the Cell

"I would like to announce that I have learned to synthesize urea without The Use of an isolated Kidney or any animal, whether human or dog." These words, written 150 years ago by the young German chemist Wöhler, marked the end of the belief in a special vital force inherent in living organisms that accounted for their distinctive features. Yet what was a revelation in Wöhler's time sounds completely commonplace today: living things are made of chemical compounds. In the modern view of life, there is no room either for vitalism or for anything that transcends the laws of chemistry and physics. This does not mean that biology has run out of mysteries; as the following chapters will show, many blank spots remain. Nevertheless, it must be emphasized right away that the volume of accumulated knowledge is truly colossal.

Today we possess detailed information about the most important molecules of The Cell—not just a small number of them, but virtually all. In many cases, we know their exact chemical Structure, as well as the pathways of their formation and breakdown. In broad terms, we understand how chemical energy sustains biosynthetic processes within the cell, how molecular order is established in accordance with the Laws of Thermodynamics, and how the myriad of incessantly occurring chemical transformations within the cell are regulated and coordinated.

In this and the following chapters, we will briefly examine The chemical properties of the living cell. Here we will discuss processes involving small molecules: the mechanisms by which the cell synthesizes its major chemical components and obtains the energy it needs. Chapter 3 will focus on giant molecules (polymers) whose properties determine the Specificity of biological processes and the transmission of biological information.

2.1.1. The Foundation of Cellular Chemistry: Carbon Compounds [1]

A living cell consists of a limited set of elements, with six of them (C, H, N, O, P, S) accounting for over 99% of its total mass. Such a composition, which differs markedly from that of the Earth's crust, points to a unique type of chemistry (Fig. 2-1). What is the distinctiveness of the chemistry of life, and how did it arise in the course of evolution?

The compound that a living cell contains in the greatest quantity is Water. It makes up about 70% of the cell's mass, and the majority of intracellular reactions take place in an aqueous environment. Life on our planet originated in the ocean, and the conditions of this primordial environment have left an indelible imprint on the chemistry of living organisms. The "design" of all living things is intimately tied to the unique properties of water, such as the polar nature of its molecules, The ability to form Hydrogen Bonds, and high surface tension (Scheme 2-1).

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Fig. 2-1. Relative Abundance of chemical elements found in the Earth's crust (the inanimate world) compared to the same elements in the soft Tissues of living organisms. Relative abundance is expressed as a percentage of the total number of atoms present. For example, hydrogen accounts for about 50% of all atoms present in living organisms.

Aside from water, virtually all cellular molecules—with few exceptions—belong to carbon compounds, which are the subject of organic chemistry. Among all the elements on Earth, carbon occupies a special place due to its ability to form large molecules; silicon possesses a somewhat analogous ability, but it falls far short of carbon in this regard. Because of its small size and the presence of four electrons in its outer shell, a carbon atom can form four strong covalent bonds with other atoms. Most importantly, carbon atoms can link to one another, forming chains and rings and thereby creating large, complex molecules whose size is seemingly without limit. Other atoms abundant in the cell (H, N, and O) are, like carbon, small in size and capable of forming very strong covalent bonds (Scheme 2-2).

In principle, the simple rules governing covalent bond formation between carbon and other elements allow for an astronomically large number of compounds. The number of different carbon compounds in the cell is indeed very large, but it represents only a tiny fraction of what is theoretically possible. In some cases, we can rather convincingly explain why a particular compound serves a specific biological function; more often, however, There is a sense that out of many viable options, one was chosen by chance (Fig. 2-2). Certain types of reactions and chemical motifs, once established, were conserved (with minor variations) throughout evolution. The Emergence of new classes of compounds was evidently necessary or advantageous in only rare instances.

2.1.2. Cells Use Four MAIN TYPES OF Molecules [2]

Specific simple combinations of atoms, such as methyl (—CH₃), hydroxyl (—OH), carboxyl (—COOH), and amino (—NH₂) groups, are repeated over and over again in biological molecules. Each such group possesses distinct chemical and physical properties that influence The behavior of any molecule containing them. An Overview of the main types of chemical groups and their individual characteristic properties is provided in Scheme 2-2.

The so-called small organic molecules of the cell are carbon compounds with a molecular weight ranging from 100 to 1000, containing up to 30 carbon atoms. Molecules of this kind are usually found in a free state within the cytoplasmic solution, forming a pool of intermediates that give rise to larger molecules known as macromolecules. They also serve as vital intermediates in Chemical Reactions that convert energy extracted from food into a usable form (see below).

Small molecules account for about one-tenth of all cellular organic matter, and an estimated thousand Different types of such molecules are present in the cell. When broken down, all biological molecules degrade into the simple compounds from which they were synthesized, with both Synthesis and Breakdown proceeding through a limited set of chemical transformations governed by specific rules. Consequently, all compounds found in the cell can be grouped into a small number of distinct families. Large macromolecules (discussed in Chapter 3) are built from small molecules and therefore belong to these same families.

Generally speaking, the small organic molecules contained within cells form four families: simple sugars, Fatty acids, Amino Acids, and NUCLEOTIDES. Each of these families encompasses many different compounds that share common chemical properties. Although some cellular compounds do not fit neatly into these categories, these four families—comprising both small molecules and the macromolecules built from them—account for a surprisingly large fraction of cellular mass (Table 2-1).

2.1.3. Sugars as Fuel for Cells [3]

Sugars of the simplest type—Monosaccharides—are compounds with the general formula (CH₂O)_n, where n is any integer from three to seven. Glucose, for example, has the formula C₆H₁₂O₆ (Fig. 2-3). As shown in Fig. 2-3, sugars can exist either in a ring form or as an open chain. Open-chain sugars contain hydroxyl groups and, in addition, either an aldehyde group or a keto group. The aldehyde and keto groups play a special role. First, they can react with a hydroxyl group on the same molecule, causing the latter to transition into a ring structure. The carbon atom of the original aldehyde or keto group can be identified by the fact that it is the only carbon atom in the molecule bonded to two oxygen atoms. Second, once the ring is formed, one of the carbon atoms bearing a hydroxyl group from another sugar molecule can attach to this carbon atom, yielding a disaccharide (Scheme 2-3). The attachment of additional monosaccharides in a similar manner leads to The formation of Oligosaccharides of increasing length (trisaccharides, tetrasaccharides, etc.) up to very large polysaccharide molecules containing thousands of monosaccharide units. Because each monosaccharide possesses multiple free hydroxyl groups capable of forming bonds with another monosaccharide or some other compound, the number of possible polysaccharide structures is exceptionally large. Even a simple disaccharide consisting of two glucose residues can exist in 11 variants (Fig. 2-4), and three different hexoses (C₆H₁₂O₆) can combine to form several thousand different trisaccharides. Therefore, determining The structure of any particular polysaccharide is an exceptionally complex task; using existing Methods, mapping the arrangement of half a dozen linked sugars (for example, in a glycoprotein) takes longer than deciphering The nucleotide sequence of a DNA molecule consisting of many thousands of nucleotides.

Scheme 2-1. Chemical properties of water and their influence on the behavior of biological molecules.

Scheme 2-2. Covalent bonds and groups found in biological molecules.

Fig. 2-2. Living organisms synthesize only a tiny fraction of all the organic molecules they could potentially form. Out of the six amino acids depicted in the figure, only the topmost one—Tryptophan—is synthesized in cells.

Table 2-1. Approximate Chemical composition of a bacterial cell

Glucose serves as the primary energy source in many cells. Through a sequential series of oxidation reactions (see Section 2.3.2), this hexose is converted into various sugar derivatives with shorter carbon chains, ultimately breaking down into CO₂ and H₂O. The overall reaction equation can be written as follows: С₆Н₁₂О₆ + СО₂ + 6СО₂ + 6Н₂О + Energy.

Fig. 2-3. STRUCTURE OF THE monosaccharide glucose, a simple hexose sugar. A. The open-chain form exists in equilibrium (in solution) with the more stable cyclic structure shown below (B). C. A space-filling model of the cyclic structure (p-D-glucose). Another possible representation of the cyclic structure is the chair conformation (D); this representation is widely used because it most accurately reflects the sugar's geometry. In all four depictions, the oxygen atom of the aldehyde group is indicated by the letter O in color. The structure and chemistry of sugars are illustrated in Scheme 2-3.

Fig. 2-4. Eleven Disaccharides composed of two D-glucose residues. Although they differ only in the type of bond linking the two glucose units, their chemical properties are distinct. Oligosaccharides attached to proteins and Lipids may contain six or more different types of sugars, forming both linear and branched structures via linkages similar to those shown in this figure. Consequently, the number of theoretically possible oligosaccharide types is extraordinarily large.

Fig. 2-5. Palmitic acid. The carboxyl group (highlighted) is shown in its ionized form. A space-filling molecular model is shown on the right.

Glucose degradation releases energy and generates reducing power, both of which are essential for biosynthetic reactions to occur. The released energy and generated reducing equivalents are stored in the form of two crucial compounds: ATP and NADH (see Section 2.3.1).

Simple polysaccharides made of repeating glucose units (primarily Glycogen in animal cells and starch in plant cells) are used for energy storage. However, sugars do not serve solely for energy acquisition and storage. For instance, simple polysaccharides constitute vital extracellular structural Materials (such as Cellulose), and non-repeating sugar chains are frequently covalently linked to proteins in Glycoproteins and to lipids in Glycolipids.

2.1.4. Fatty Acids: Components of Cell Membranes

A fatty acid molecule, such as palmitic acid (Fig. 2-5), consists of two distinct parts: a long hydrocarbon chain that is hydrophobic (water-insoluble) and chemically inert, and a carboxyl group that ionizes in solution, is extremely hydrophilic (water-soluble), and readily forms esters and amides. In fact, in almost all cellular contexts, fatty acid molecules are covalently linked to other molecules precisely through their carboxyl groups. The various fatty acids found in cells differ in chemical properties such as hydrocarbon chain length, as well as the number and position of carbon–carbon double bonds (Scheme 2-4).

Scheme 2-4. Some common types of fatty acids found in cells and the structures they form.

Fatty acids are a rich source of energy, as their oxidation yields twice as much ATP as The breakdown of an equal mass of glucose. Fatty acids are stored in the Cytoplasm of many cells as lipid droplets composed of triacylglycerols (triglycerides). Triacylglycerol molecules consist of three fatty acid chains, each esterified to a glycerol molecule (Scheme 2-4); this is the structure of the animal fats we encounter in everyday life. When needed, fatty acid chains can be cleaved from triacylglycerols and broken down into two-carbon units. Released as acetyl groups within a water-soluble molecule known as acetyl-CoA, these two-carbon units undergo further degradation through various exergonic reactions discussed in subsequent sections.

However, the most vital function of fatty acids is their Participation in the construction of cell membranes. These thin, dense sheets enclosing all cells and intracellular Organelles are composed primarily of Phospholipids—small molecules similar to triacylglycerols in that they contain fatty acid components linked to glycerol. Unlike triacylglycerols, however, phospholipids typically have only two fatty acid chains attached to glycerol rather than three. The remaining site on the glycerol molecule is normally occupied by a phosphate group, which in turn is linked to one of several small hydrophilic HEAD groups, such as ethanolamine, Choline, or Serine.

Each phospholipid molecule features a hydrophobic tail consisting of two fatty acid chains and a hydrophilic polar head containing the phosphate group. Due to these properties, phospholipid molecules behave essentially as detergents. A small amount of phospholipids spread across a water surface will form a phospholipid monolayer, in which tightly packed tails project into the air while the heads are immersed in water (Scheme 2-4). Two such layers can associate tail-to-tail to form a phospholipid "sandwich," or lipid bilayer, which serves as the structural basis for all cell membranes.

2.1.5. Amino Acids: Subunits of Proteins

Amino acids found in biological tissues vary in their chemical composition. Nevertheless, they all share the common feature of possessing a carboxyl group and an amino group attached to the same carbon atom (Fig. 2-6). Amino acids serve as the building blocks for proteins—long, linear polymers of amino acids joined head-to-tail via peptide bonds formed between the carboxyl group of one Amino Acid and the amino group of another (Fig. 2-7). Proteins typically contain 20 different amino acids with distinct side chains attached to the a-carbon atom (Scheme 2-5). The exact same set of 20 amino acids is used repeatedly across all proteins, including those of bacterial, animal, and plant origin. While the evolutionary Selection of these specific 20 amino acids may be partly a matter of chance, their chemical diversity is of vital importance.

Fig. 2-6. The amino acid Alanine in the ionized form characteristic of physiological pH 7. When alanine is incorporated into a polypeptide chain, the charges on the amino and carboxyl groups of the free amino acid are lost. A space-filling model is shown at the bottom.

Fig. 2-7. A small portion of a protein molecule. The four amino acids shown here are linked together by covalent bonds known as peptide bonds, which is why a protein can also be referred to as a polypeptide. The amino acid side chains are highlighted in color.

Panel 2-5. The 20 amino acids involved in Protein Synthesis.

Fig. 2-8. The charge of amino acid side chains depends on the pH. In aqueous solutions, carboxylic acids readily lose an H⁺ ion to form a negatively charged ion designated by the suffix "-ate", such as aspartate or glutamate. A comparable situation occurs with amines, which capture an H⁺ ion in aqueous solution and become positively charged ions (which have no special designation). These reactions are readily reversible, and the relative amounts of the two forms (charged and uncharged) depend on the pH of the solution. At high pH values, carboxylic acids tend to acquire a charge, whereas amines remain uncharged. At low pH values, the situation is reversed: carboxylic acids are uncharged, and amines are positively charged. The pH at which exactly half of the carboxylic acid or amine residues are charged is called the pK of the amino acid. Within the cell, the pH is close to 7, and nearly all carboxylic acids and amines exist in their charged state.

For example, 5 out of the 20 Amino acids have side chains that can carry a charge (Fig. 2-8), whereas the side chains of the Other Amino Acids are electroneutral yet capable of participating in reactions through the formation of specific bonds (Panel 2-5). As we will see, the specific Properties of the side chains of all amino acids within a given protein determine its characteristics and underlie the complex and diverse Functions of protein molecules.

2.1.6. Nucleotides: Subunits of DNA and RNA [5]

In nucleotides, one of several nitrogen-containing cyclic compounds (often called bases because they can accept an H⁺ ion in an acidic environment) is linked to a five-carbon sugar (ribose or deoxyribose), which also bears a phosphate group. The nitrogen-containing rings found in nucleotides are closely related structurally. Cytosine (C), thymine (T), and uracil (U) are termed pyrimidine bases because they are simple derivatives of a six-membered pyrimidine ring; guanine (G) and adenine (A) are purine bases, in which a five-membered ring is fused to a six-membered ring. Each nucleotide is named after the unique base it incorporates (Panel 2-6).

Panel 2-6. The principal types of nucleotides and their derivatives found in cells.

Fig. 2-9. Chemical Structure of adenosine triphosphate (ATP). A space-filling model (A) and a structural formula (B) of the molecule are shown.

Fig. 2-10. A short segment of deoxyribonucleic acid, or DNA. DNA and the closely related RNA are the nucleic acids of the cell.

The DNA chain segment shown in the figure contains the nucleotide sequence G-A-T-C.

Nucleotides can act as energy carriers. Among them, the adenine triphosphate ester ATP (Fig. 2-9) participates far more frequently than other nucleotides in energy transfer between hundreds of individual intracellular reactions. The terminal phosphate of ATP forms a covalent bond during The oxidation of nutrients; The energy released upon the Hydrolysis of this phosphate group can be utilized elsewhere to drive energy-requiring biosynthetic processes. Other nucleotide derivatives serve as carriers of chemical groups, such as hydrogen atoms or sugar residues, transferring them from one molecule to another. In addition, a cyclic phosphorylated derivative of adenine—cyclic AMP (cAMP)—serves as a universal intracellular signal regulating The rate of numerous distinct intracellular reactions.

As mentioned in Chapter 1, nucleotides play a particularly vital role in the Storage of Biological information. Nucleotides serve as the building blocks for the synthesis of nucleic acids—long polymers in which nucleotide subunits are linked together by covalent bonds, forming a phosphodiester linkage between the 3'-hydroxyl group of one nucleotide's sugar residue and the 5'-phosphate group of the next (Fig. 2-10). There are two main Types of Nucleic acids, differing in the type of sugar that makes up their polymer backbone. Nucleic acids containing ribose are called Ribonucleic Acids, or RNA; they contain the bases A, U, G, and C. Those containing deoxyribose (in which the hydroxyl group at the C-2 position of ribose is replaced by a hydrogen atom) are called Deoxyribonucleic Acids, or DNA; they contain the bases A, T, G, and C. The sequence of bases within DNA and RNA polymer molecules encodes the Genetic information of the living cell. The ability of nitrogenous bases in different nucleic acid molecules to "recognize" one another through noncovalent interactions (termed base-pairing)—G with C, and A with T or U—forms the foundation of the mechanisms of heredity and evolution. This subject is examined in the next chapter.

Conclusions

Living organisms are self-sustaining, self-replicating chemical systems. They are constructed from a specific yet limited set of carbon-based small molecules, which are generally identical across all species of living creatures. The Major Groups of these molecules are sugars, fatty acids, amino acids, and nucleotides. Sugars serve as a vital energy source for cells and store energy in the form of Reserve Polysaccharides. Fatty acids, much like sugars, are essential for energy storage, but their most crucial function is the formation of cell membranes. Polymers built from Amino acids are represented by remarkably diverse and multifunctional protein molecules. Nucleotides participate in Intracellular Signaling and play a central role in energy transfer, yet their unique significance lies in serving as the subunits of the informational molecules RNA and DNA.