Lecture 1. Foundations

Introduction to the course. Inventory of concepts from prior courses that are important for biochemistry.

Reading: Voet, Voet and Pratt, 4th ed. (VVP4e); Chapters 1 and 2.

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Summary

We begin our semester-long journey exploring the chemistry of life by taking an inventory of the concepts and principles developed in the biology and chemistry courses you've taken up to this point. The list of courses we developed includes General Chemistry [CHEM 101], Organic Chemistry I & II [CHEM 230, 331], Bioanalytical Chem [CHEM 240], Quantitative Analysis [CHEM 310], Information Flow in Biological Systems [BIOL 105], Energy flow in Biological Systems [BIOL 106], Genetics [BIOL 207]. Note that many of the concepts we'll find relevant are reviewed in the reading assignment (Chs. 1 & 2 of Voet, Voet, and Pratt).

Chemical foundations

Among the important chemical concepts for biochemistry, we have the following:

 

• Aqueous solutions
  • Properties of water as a solvent
  • Aqueous chemistry: acid-base reactions
    • Definitions of pH, pK_a, etc.
    • Buffers and the Henderson-Hasselbalch equation
• Functional groups
  • It is important to know the common functional groups from organic chemistry, their properties and reactivities (for a list, see Table 1.2, p.4 in the text).
  • Examples of ionizable functional groups (carboxyl/carboxylate and protonated amine/amine conjugate pairs) with pH-dependent charge states. We will not memorize pK values, but it is important to have a "ballpark" idea of the values and know the order of acid strength of the various acidic functional groups.
• Nomenclature
• Redox reactions
  • Oxidation-reduction, or "redox", reactions figure prominently in metabolism. An example is provided by the electron transport protein cytochrome c.
• Chemical kinetics: The velocity of chemical reactions
  • Enzyme kinetics: Enzymes are biological catalysts that greatly speed up the rates of specific spontaneous chemical reactions.
• Thermodynamics
  • Living organisms obey the laws of thermodynamics!
  • A spontaneous process is one that is thermodynamically favored; however, the thermodynamic favorability of a process does not imply anything about its rate (kinetics).
  • For processes occurring in a system at constant temperature, the Gibbs free energy function (G) is used to assess spontaneity:
    • ΔG < 0 for the process ⇔ process is spontaneous
• Covalent (bonding) interactions and noncovalent interactions
  • It is quite important to understand the distinction between covalent or ionic bonding and noncovalent forces.
  • Noncovalent forces determine the conformations (shapes) of biological macromolecules and the interactions between molecules (see below for a summary of noncovalent forces)

 

Noncovalent 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 noncovalent 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 specifies biomolecular structure: electrostatic interactions, van der Waals forces, and hydrogen bonds. These can be thought of as contributing to enthalpy in processes such as protien folding and formation of complementary double-stranded DNA from the separated single strands. In addition, we discuss the hydrophobic effect, which arises as a result of entropic contributions of water solvation of nonpolar surface area.

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 are able to sustain a dynamic, non-equilibrium steady-state. Furthermore, cells have the ability to self-replicate, by mitosis, and form higher order associations as multicellular organisms. The internal environment of cells is regulated, and levels of ions, metabolites, 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
  • Prokaryotes 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: bacterial 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 molecular 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.