Lecture 1 Summary

We begin our semester-long journey exploring the chemistry of life by considering the striking unity at the molecular level that underlies the biological diversity throughout the three domains of life: Archaea, Bacteria, and Eukarya. At a microscopic level, living systems are composed of cells, either in isolation as single cells, or in complex multicellular organisms. Thus, cells represent a kind of fundamental building block of living organisms, yet even among cells there exists an incredible morphological variety. To truly understand cells, one must descend all the way to the molecular level - to atomic resolution - and there find the common features, such as primary metabolism and molecular mechanisms of heredity and gene expression. To be sure, there is diversity at the molecular level as well, but this is secondary to the identities and close similarities (or homologies) among molecules and the functions they carry out, as found in the tremendous range of living species studied by the methods of molecular biology.

The cellular nature of life

Cells are spatially defined as membrane-bounded microsystems of great functional and compositional complexity. They are thermodynamically open systems that able to sustain a dynamic, non-equilibrium steady-state. Furthermore, cells have the abilty to self-replicate, by mitosis, and form higher order associations as multicellular organisms. The internal environment of cells is regulated, and levels of ions, metabolities, chemical energy, reducing potential, and transmembrane electrochemical potential, are maintained within typically narrow ranges. This characteristic of cells, referred to as cellular homeostasis is apparently for their continued survival. One of the central tasks that concerns biochemistry is a complete molecular-level description of the mechanisms underlying homeostasis and self-replication.

Among the topics where there is a large intersection between cell biology and biochemistry are

• Compartmentation, catalysts, precursors, energy sources
• The distinction between prokaryotes and eukaryotes; eukaryotic organelles
  • Prokarayotes lack a nucleus or other membrane-bound organelles
  • Eukaryotes have specialized membrane-bound organelles: e.g. mitochondria, chloroplasts .
• Mechanical properties of cells and their ability to generate kinetic energy
  • Cytoskeletal structure
  • Motility: bacerial flagella
  • Muscle contraction: myofibrils

The major classes of biological molecules

The major classes of biological molecules are proteins, nucleic acids, carbohydrates, and lipids. These molecules are characteristically very large - much larger than the "small" molecules we are used to dealing with in introductory chemistry courses. Thus, we often refer to these as biological macromolecules, which commonly have molecular masses in the range several thousand on up to millions of atomic mass units (amu). In biochemistry, instead of the amu, the equivalent unit dalton (D or Da) is used. The molcular weights of biological macromolecules are most conveniently expressed in kilodaltons (kD). Our initial goal is to learn the basic covalent structures of these classes of molecules, and relate them to some of their properties or functions. For example, proteins are polymers of amino acids covalently linked together in a specific sequence by amide bonds. These linkages are given the special name peptide bonds, and the chains of amino acids that make up proteins are referred to as polypeptide chains or polypeptides.

Non-covalent forces that determine macromolecular structure

One of the major themes of biochemistry is how biomolecular structure determines function. Of course we must know the covalent structure of the molecules of life, but the functional implications depend on a detailed picture of the conformations adopted by these molecules. Because of the sheer size of biological macromolecules, an astronomical number of conformations are possible in principle. That molecules such as proteins and nucleic acids in fact assume a unique structure, or a very restricted range of conformations, has something to do with the relationship between a particular conformation and the energy associated with it. A knowledge of non-covalent forces is essential to an understanding of biomolecular structure, since these determine the energetics of conformations and the interactions between molecules in defined conformational states. There are several kinds of forces that play predominant roles in defining the energetic landscape that in turn determines biomolecular structure, and we will consider each of them separately. They are electrostatic interactions, van der Waals forces, hydrogen bonds, and hydrophobic effects.

Discussion topic

The following considerations may serve as a stimulus to further thought or class discussion. There is long history of vitalism underlying our attempts to explain the fundamental nature of life. The doctrine of vitalism is encapsulated in the antiquated idea that an "organic" compound could never arise from strictly inorganic starting materials. Vitalism claims an exceptionalism for living things: that the laws of physics and chemistry do not apply or are somehow incomplete when it comes to life. More modern "creationist" arguments that the complexity of life violates the second law betray an egregious misunderstanding of thermodynamics, since life on earth depends on energy supplied by thermonuclear reactions in the sun or geothermal energy. Locally, entropy may decrease, but the overall entropy of a larger portion of the universe (e.g. the solar system) increases according to the second law of thermodynamics. What many experts consider an updated, more sophisticated version of creationist thinking is represented by the proponents of "intelligent design". The general argument made is that the complexity of living cells and even their component systems is such that they could not have arisen by the mechanisms of "Darwinian" evolution, and that they therefore must owe their existence to the "design" (and presumably production) efforts of an intelligent agency.

Learning objectives

• Name the major classes of biological molecules, and describe their biological roles.
• Identify the major types of noncovalent interactions that are important in determining biomolecular structures.
• Describe the characteristics of hydrogen bonds, electrostatic and van der Waals interactions.

Page updated 9-13-09

References

1. Asimov, I. Life and Energy (1962, Doubleday). This is a classic by my lights, worth reading if you can find it. Reading this book in high school convinced me to become a biochemist!
2. Creighton, TE. Proteins: Structure and Molecular Properties (2nd ed, 1993. Freeman).
3. Atkins, PW, de Paula, J. Physical Chemistry for the Life Sciences (2006, Freeman/Oxford Univ. Press)
4. Chang, R. Physical Chemistry for the Biosciences (2005, University Science Books)