xx part Foundations of Biochemistry I 1 The Molecular Logic of Life facing page 2 Cells The Orion Nebula, a tremendous cloud of gas in which many hot, young stars are evolving rapidly toward cata- 3 Biomolecules clysmic cosmic explosions called supernovae. Energy released by nuclear explosions in such supernovae 4 Water brought about the fusion of simple atomic nuclei, forming the more complex elements of which the earth, Fifteen to twenty billion years ago, the universe arose as a cataclysmic its atmosphere, and all living things are composed. eruption of hot, energy-rich subatomic particles. Within seconds, the sim- plest elements (hydrogen and helium) were formed. As the universe ex- panded and cooled, material condensed under the influence of gravity to form stars. Some stars became enormous and then exploded as supernovae, releasing the energy needed to fuse simpler atomic nuclei into the more complex elements. Thus were produced, over billions of years, the earth it- self and the chemical elements found on the earth today. About four billion years ago, life arose—simple microorganisms with the ability to extract en- ergy from organic compounds or from sunlight, which they used to make a vast array of more complex biomolecules from the simple elements and compounds on the earth’s surface. Biochemistry asks how the thousands of different biomolecules interact with each other to confer the remarkable properties of living organisms. In Part I, we will summarize the biological and chemical background to biochemistry. Living organisms obey the same physical laws that apply to all natural processes, and we begin by discussing those laws and several ax- ioms that flow from them (Chapter 1). These axioms make up the molecu- lar logic of life. They define the means by which cells transform energy to accomplish work, catalyze chemical transformations, assemble complex molecules from simpler subunits, form supramolecular structures that are the machinery of life, and store and pass on the instructions for the assem- bly of all future generations of organisms from simple, nonliving precursors. Cells, the units of all living organisms, share certain features; but the cells of different organisms, and the various cell types within a single or- ganism, are remarkably diverse in structure and function. Chapter 2 is a brief description of the common features and the diverse specializations of cells, and of the evolutionary processes that have led to such diversity. Nearly all of the organic compounds from which living organisms are constructed are products of biological activity. These molecules were se- lected during the course of biological evolution for their fitness in perform- ing specific biochemical and cellular functions. Biomolecules can be char- acterized and understood in the same terms that apply to molecules of inanimate matter: the types of bonds between atoms, the factors that con- tribute to bond formation and bond strength, the three-dimensional 1 2 Part I Foundations of Biochemistry structures of molecules, and chemical reactivities. Three-dimensional structure is especially important in biochemistry. Biological interactions, such as those between enzyme and substrate, antibody and antigen, hor- mone and receptor, are highly specific, and this specificity is achieved by steric and electrostatic complementarity between molecules. Prominent among the forces that stabilize three-dimensional structure are noncovalent interactions, individually weak but with significant cumulative effects. Chapter 3 provides the chemical basis for later discussions of the structure, catalysis, and metabolic interconversions of individual classes of biomole- cules. Water is the medium in which the first cells arose, and it is the solvent in which most biochemical transformations occur. The properties of water have shaped the course of evolution, and the structure and interactions of biomolecules are profoundly influenced by the aqueous solution in which biomolecules reside. The weak interactions within and between biomole- cules are strongly affected by the solvent properties of water. Even water- insoluble components of cells, such as membrane lipids, interact with each other in ways dictated by the polar properties of water. In Chapter 4 we consider the properties of water, the weak noncovalent interactions that oc- cur in aqueous solutions of biomolecules, and the ionization of water and of solutes in aqueous solution. These initial chapters are intended to provide a chemical backdrop for the later discussions of biochemical structures and reactions, so whatever your background in chemistry or biology, you can immediately begin to fol- low, and to enjoy, the action. chapter The Molecular Logic of Life 1 Living organisms are composed of lifeless molecules. When these molecules are isolated and examined individually, they conform to all the physical and chemical laws that describe the behavior of inanimate matter. Yet living or- ganisms possess extraordinary attributes not exhibited by any random col- lection of molecules. In this chapter, we first consider the properties of liv- ing organisms that distinguish them from other collections of matter, and then we describe a set of principles that characterize all living organisms. These principles underlie the organization of organisms and their cells, and they provide the framework for this book. They will help you to keep the larger picture in mind while exploring the illustrative examples presented in the text. (a) The Chemical Unity of Diverse Living Organisms What distinguishes living organisms from inanimate objects? First is their degree of chemical complexity and organization. Thousands of different molecules make up a cell’s intricate internal structures (Fig. 1–1a). By con- trast, inanimate matter—clay, sand, rocks, seawater—usually consists of mixtures of relatively simple chemical compounds. Second, living organisms extract, transform, and use energy from their environment (Fig. 1–1b), usually in the form of chemical nutrients or sun- (b) light. This energy enables organisms to build and maintain their intricate structures and to do mechanical, chemical, osmotic, and other types of work. Inanimate matter does not use energy in a systematic, dynamic way to maintain structure or to do work; rather, it tends to decay toward a more disordered state, to come to equilibrium with its surroundings. The third attribute of living organisms is the capacity for precise self- replication and self-assembly, a property that is the quintessence of the liv- ing state (Fig. 1–1c). A single bacterial cell placed in a sterile nutrient medium can give rise to a billion identical “daughter” cells in 24 hours. Each of the cells contains thousands of different molecules, some extremely com- plex; yet each bacterium is a faithful copy of the original, its construction directed entirely from information contained within the genetic material of (c) the original cell. Although the ability to self-replicate has no true analog in the nonliving figure 1–1 Some characteristics of living matter. (a) Microscopic world, there is an instructive analogy in the growth of crystals in saturated complexity and organization are apparent in this colorized solutions. Crystallization produces more material identical in lattice struc- thin section of vertebrate muscle tissue, viewed with the ture to the original “seed” crystal. Crystals are much less complex than the electron microscope. (b) A prairie falcon acquires nutri- simplest living organisms, and their structure is static, not dynamic as are ents by consuming a smaller bird. (c) Biological repro- living cells. Nevertheless, the ability of crystals to “reproduce” themselves duction occurs with near-perfect fidelity. 3 4 Part I Foundations of Biochemistry led the physicist Erwin Schrödinger to propose in his famous essay “What Is Life?” that the genetic material of cells must have some of the properties of a crystal. Schrödinger’s 1944 notion (years before our modern under- standing of gene structure) describes rather accurately some of the prop- erties of deoxyribonucleic acid, the material of genes. Each component of a living organism has a specific function. This is true not only of macroscopic structures, such as leaves and stems or hearts and lungs, but also of microscopic intracellular structures such as the nu- cleus or chloroplast and of individual chemical compounds. The interplay among the chemical components of a living organism is dynamic; changes in one component cause coordinating or compensating changes in another, Erwin Schrödinger with the whole ensemble displaying a character beyond that of its individ- 1887–1961 ual constituents. The collection of molecules carries out a program, the end result of which is reproduction of the program and self-perpetuation of that collection of molecules; in short, life. Biochemistry Explains Diverse Forms of Life in Unifying Chemical Terms If living organisms are composed of molecules that are intrinsically inani- mate, how do these molecules confer the remarkable combination of char- acteristics we call life? How can a living organism be more than the sum of its inanimate parts? Philosophers once answered that living organisms are endowed with a mysterious and divine life force, but this doctrine, called vi- talism, has been firmly rejected by modern science. The study of biochem- istry shows how the collections of inanimate molecules that constitute liv- ing organisms interact to maintain and perpetuate life animated solely