6.1. (Very) Brief Refresher of the Basics
A quick reminder of some of the material previously covered will help keep the rest of the chapter in context.
Recall that amino acids are a class of bioorganic compounds that contain an amine group and a carboxylic acid. Twenty amino acids are very common in organisms and merit special attention (Figure 4.3).
Figure 4.3 – Trivial Name, Three-Letter Code, One-Letter Code, Structure, and pKa Values for The Twenty Common Amino Acids.
There are several different ways of grouping these amino acids by their side chains. In very broad terms, the groups can be classed by whether they are polar or not (viz. hydrophilic or hydrophobic). Additionally, many of the side chains have functional groups that are capable of other interactions (e.g. hydrogen bonding, pi-stacking, ionic bonds, etc.) and/or chemical reactions (e.g. acid-base reactions, nucleophile-electrophile reactions, etc.).
6.1.2. Peptide Folding and Structural Complexity
Recall that certain patterns in the ways that long chain peptides fold and create three-dimensional structures are very consistent. These shapes result from sets of amino acids along the chain interacting with each other in regular (repeating) ways. Often this is the result of non-covalent interactions and/or rigidity/flexibility of the chain. While this is heavily influenced by the specific side chains of the amino acids, the exact amino acids required can be highly variable; these shapes can result from MANY different arrangements of amino acids provided they have the required interactions. Some of the more common shapes include alpha-helixes (α-helixes), beta-sheets (β-sheets), and loops (Figure 6.1).
Figure 6.1 – An Alpha- (α-) Helix, Beta- (β-) Sheet, and Loop in Ribbon Model.
Recall that these shapes themselves often combine to form larger, even more complex structures. Generally, discussions of peptide structures divide the topic into four parts (Figure 6.2). The primary structure is the sequence of amino acids itself. The secondary structure is the sequence of local substructures (the sequence of common folding patterns). The tertiary structure is the final overall shape that the peptide sequence adopts. The quaternary structure is the shape(s) of the overall structure when multiple folded peptide chains (tertiary structures) combine to form a larger structure.
Figure 6.2 – Examples of Primary, Secondary, Tertiary, and Quaternary Structures.
As a result of the large size and complexity of proteins/enzymes they are typically abbreviated when drawn to only show the relevant part(s). This is especially common when discussing mechanisms involving enzyme catalysis.
Recall that catalysis is a broad field of study focused on improving the speed of chemical reactions. Catalysis may allow some reactions which could not otherwise occur take place. The general idea is to use some compound, which is not consumed in the reaction, to either make an energetically impossible reaction possible or make a slow reaction faster than it would otherwise be.
A common misconception is that catalysis accelerates reactions by lowering the activation energy. This is effectively true, but inaccurate. More specifically, catalysis provides an alternative pathway for the reaction to proceed through. This means that the transition states and intermediates are different from the uncatalyzed reaction, and these different species have different (lower) activation energies (Figure 6.3). Additional steps in the pathway (and new intermediates and transition states) are often added. Recall that the number of steps in the reaction does not affect the overall reaction rate. For example, a reaction with one step (one transition state) can be slower than a reaction with fifty steps.
Figure 6.3 – Comparison of Uncatalyzed and Catalyzed Reaction Coordinates for a Hypothetical Reaction.
Catalysis only affects the overall speed of reactions (kinetics), it does not change the relative energies of the starting materials and products (thermodynamics). As a result, catalysis does not affect equilibrium ratios (the relative amounts of starting materials and products at equilibrium). A system may be able to reach equilibrium faster through catalysis, but it cannot be biased towards making more or less of the product than equilibrium would allow via catalysis alone.
