Chapter 2: Chemical Foundations

Chapter Introduction

CHAPTER 2

Chemical Foundations

“Star of David” catenane. Two triply entwined rings composed of carbon, hydrogen, and nitrogen are linked together with bridging iron atoms via a complex chemical synthetic pathway to cross each other six times and form a hexagram (six-pointed star). The chemical structure is indicated on the left, where the two independent rings are colored blue and orange. On the right is the three-dimensional structure determined by x-ray crystallography with the carbon atoms of one ring in blue and the other light gray; irons are pink and nitrogens purple. In the center is a noncovalently bound, negatively charged phosphorus hexafluoride (cyan and green).

See D. A. Leigh, R. G. Pritchard, and A. J. Stephens, 2014, Nature Chem. 6:978–982.

OUTLINE

2.1 Covalent Bonds and Noncovalent Interactions

2.2 Chemical Building Blocks of Cells

2.3 Chemical Reactions and Chemical Equilibrium

2.4 Biochemical Energetics

The life of a cell depends on thousands of chemical interactions and reactions exquisitely coordinated with one another in time and space, influenced by the cell’s genetic instructions and its environment. By understanding these interactions and reactions at a molecular level, we can begin to answer fundamental questions about cellular life: How does a cell extract nutrients and information from its environment? How does a cell convert the energy stored in nutrients into the work of movement or metabolism? How does a cell transform nutrients into the cellular components required for its survival? How does a cell link itself to other cells to form a tissue? How do cells communicate with one another so that a complex, efficiently functioning organism can develop and thrive? One of the goals of Molecular Cell Biology is to answer these and other questions about the structure and function of cells and organisms in terms of the properties of individual molecules and ions.

For example, the properties of one such molecule, water, control the evolution, structure, and function of all cells. An understanding of biology is not possible without appreciating how the properties of water control the chemistry of life. Life first arose in a watery environment. Constituting 70–80 percent of most cells by weight, water is the most abundant molecule in biological systems. It is within this aqueous milieu that small molecules and ions, which make up about 7 percent of the weight of living matter, combine into the larger macromolecules and macromolecular assemblies that make up a cell’s machinery and architecture and thus the remaining mass of organisms. These small molecules include amino acids (the building blocks of proteins), nucleotides (the building blocks of DNA and RNA), lipids (the building blocks of biomembranes), and sugars (the building blocks of complex carbohydrates).

Many of the cell’s biomolecules (such as sugars) readily dissolve in water; these molecules are referred to as hydrophilic (“water liking”). Others (such as cholesterol) are oily, fatlike substances that shun water; these molecules are said to be hydrophobic (“water fearing”). Still other biomolecules (such as phospholipids) contain both hydrophilic and hydrophobic regions; these molecules are said to be amphipathic or amphiphilic (“both liking”). The smooth functioning of cells, tissues, and organisms depends on all these molecules, from the smallest to the largest. Indeed, the chemistry of the simple proton (H⁺) can be as important to the survival of a human cell as that of each gigantic DNA molecule (the mass of the DNA molecule in human chromosome 1 is 8.6 × 10¹⁰ times that of a proton!). The chemical interactions of all these molecules, large and small, with water and with one another define the nature of life.

Luckily, although many types of biomolecules interact and react in numerous and complex pathways to form functional cells and organisms, a relatively small number of chemical principles are necessary to understand cellular processes at the molecular level (Figure 2-1). In this chapter, we review these key principles, some of which you already know well. We begin with the covalent bonds that connect atoms into molecules and the noncovalent interactions that stabilize groups of atoms within and between molecules. We then consider the basic chemical building blocks of macromolecules and macromolecular assemblies. After reviewing those aspects of chemical equilibrium that are most relevant to biological systems, we end the chapter with the basic principles of biochemical energetics, including the central role of ATP (adenosine triphosphate) in capturing and transferring energy in cellular metabolism.

FIGURE 2-1 Chemistry of life: four key concepts. (a) Molecular complementarity lies at the heart of all biomolecular interactions (see Section 2.1), as when two proteins with complementary shapes and chemical properties come together to form a tightly bound complex. (b) Small molecules serve as building blocks for larger structures (see Section 2.2). For example, to generate the information-carrying macromolecule DNA, four small nucleotide building blocks are covalently linked into long strings (polymers), which then wrap around each other to form the double helix. (c) Chemical reactions are reversible, and the distribution of the chemicals between starting reactants (left) and the products of the reactions (right) depends on the rate constants of the forward (k_f, upper arrow) and reverse (k_r, lower arrow) reactions. The ratio of these, K_eq, provides an informative measure of the relative amounts of products and reactants that will be present at equilibrium (see Section 2.3). (d) In many cases, the source of energy for chemical reactions in cells is the hydrolysis of the molecule ATP (see Section 2.4). This energy is released when a high-energy phosphoanhydride bond linking the b and g phosphates in the ATP molecule (red) is broken by the addition of a water molecule, forming ADP and P_i.