CHEM251-2018A-002.

Principles of Biological Chemistry

Spring 2018

Tip sheet for Midterm 2 (Version 1)

(adapted from Tip sheet for Midterm 1, Version 1)

Text: Voet, Voet & Pratt. Fundamentals of Biochemistry

Here are some suggestions to help you focus your studying. See below for items specific to
Midterm 2.

Chapter 1. Introduction to the Chemistry of Life & Thermodynamics

Suggestions:
• Be able to list differences comparing bacterial and eukaryotic cells.
• Know the chemical structure of the functional groups discussed in class.
• Be able to use stereochemistry concepts, in as far as discussed in class.
• Thermodynamics. Know and be able to use equations and concepts of
thermodynamics as presented: equilibria, second law, free energy and standard
partial molar free energy change.
• Understand what is meant by “partial molar Gibbs energy” or “chemical
potential.”
• Know and understand the equations that determine the partial molar Gibbs energy
that we presented in class.
• Be able to discuss how systems will evolve with regard to redistribution of the
molecular species involved, e.g., across a chemical reaction, as the system
establishes equilibrium

Chapter 2. Water & Acid-Base Chemistry

Suggestions

• Understand the noncovalent interactions discussed in class

• Understand the hydrophobic effect
• Understand and be able to apply concepts related to pH, pKa, and buffering
• Be able to derive and apply formulas for calculating the fraction of a molecular
species that is protonated or deprotonated as a function of pH
• Be able to determine fractional charge on a molecular species with ionizable
groups as a function of pH
• Be able to describe how the pKa of an acidic group can be modified based up on
stabilization of the conjugate acid or base

Chapter 4. Amino acids

Suggestions
 • Know the chemical structure of the 20 common (naturally occurring) amino acids
and understand differences in their chemical properties. While learning chemical
structures, focus on important molecular features and properties.
• Know the names and abbreviations (three- and one-letter codes) for all 20
common amino acids
• Know the approximate (integer value) pKa values of: alpha carboxyl group, alpha
amino group, and ionizable side chains of the amino acids.
• Know the stereochemistries of common amino acids.
• Understand the concept of pI (isoelectric point) and how to obtain pI for an amino
acid from the pKa values of the ionizable groups.
• Be able to determine the net charge of an amino acid sequence at given pH. (Here
you may assume that the pKa’s of the ionizable groups are unperturbed by the
presence of other functional groups in a given peptide.)
• Be able to draw and explain the titration curve of an amino acid with a side chain
that can undergo an acid/base reaction.
• Note that amino acid side chains (R groups) can be sites of chemical modification
of the amino acids

Chapters 4-5. Protein Primary and Secondary Structure

• Be able to draw the chemical structure of short peptides given the sequence of
amino acids
• Be able to write down the sequence of a peptide given its structure
• Understand what is meant by torsional angle and the three angles per amino acid
that are used in describing the backbone structures of peptides.
• Be able to describe alpha-helical secondary structure, the dimensions of alpha
helices, and the number of amino acid residues per turn of the helix, and how
amino acids are presented on the exterior of the helix.
• Understand the polarity of alpha helices.
• Be able to describe and sketch the nature of the hydrogen bonding observed in
alpha helices and beta sheets.
• Know the dimensions associated with the spacing between strands in parallel and
antiparallel beta sheet structures.
• Be able to explain why some amino acids may have difference propensities for
alpha helical or beta sheet structures.

--- Midterm Exam 2 ---

Peptide & Protein Structure

• Know the general principles and steps associated with synthesizing a peptide on a
solid support
• Know which parts of the peptide backbone are rigid, planar and which are
variable with regard to rotation
• Describe phi, psi and the atoms involved in defining these angles
 • Understand the dimensions and arrangement of amino acids in alpha helices and
beta sheets
• How do parallel and antiparallel beta sheets differ?
• Understand the allowed regions of the Ramachandran map and where common
secondary structures are located
• Describe the hierarchical classification types of protein structure: primary,
secondary, tertiary, quaternary
• What molecular properties stabilize folded protein structures?
• Understand the Levinthal paradox
• Describe pathway and energy landscape pictures of protein folding
• What is meant by assisted folding and why is it sometimes necessary?
• There will be no questions on the exam concerning structure determination using
x-ray diffraction or NMR methods.
• You should understand how the stability (free energy of folded) of the folded state
can be quantified using a two-state (folded, unfolded) model. How can the
enthalpy and entropy of folding be estimated by varying the temperature? What
assumptions are present?

Protein Function

Focus on reversible binding, myoglobin and hemoglobin. The exam will not include
questions from other sections (Antibodies, Molecular Motors, etc.).

• Understand “lock and key” and “induced fit” models of binding.

• You should be familiar with the chemical equilibria involving binding of one
molecule to another: Ka, Kd, free energy of binding, fraction of protein bound.
• Be able to describe the O2 binding site in myoglobin and hemoglobin and its
chemical features that re used to modulate binding.
• Graphically be able to sketch and describe a plot of fraction bound vs.
concentration of free ligand.
• Be able to describe cooperative binding and how hemoglobin binds oxygen
cooperatively.
• Describe the assumptions of a Hill plot and analysis and how this is used to
quantify cooperativity.
• How is the binding of hemoglobin regulated?
• How does pH impact the oxygen affinity of hemoglobin and how does this impact
the physiological transport of O2 and CO2 ? Be able to describe (qualitatively) the
Bohr effect?
• Be able to describe how a mutation to hemoglobin leads to sickle cell anemia?

Enzymes

Read the entire chapter. Among the examples, focus on the mechanism of the serine
proteases (e.g., chymotrypsin and trypsin).
• Understand the role of enzymes and the generic principles by which they achieve
increased reaction rates.
• Understand the impact of enzymes on rates of reactions and their chemical
equilibria.
• Understand the derivation of Michaelis-Menten kinetics, the meaning of the
parameters that appear, and the effects of inhibitors.
• Be able to describe how the efficiency and specificity of an enzyme are
quantified.
• Be able to sketch plots of reaction rate vs. substrate concentration and the double-
reciprocal plots (1/rate vs 1/[S]).

• Understand the role of enzyme-substrate binding and its role in catalysis and
reaction specificity.
• Be able to describe general acid/base and covalent catalysis.
• For serine proteases, how do specific chemical groups contribute to the catalysis
of the reaction.
• Be able to discuss the complementarity of enzymes to substrates, intermediates
and transition states. How can this knowledge be used to design inhibitors of
enzymes?
• Understand the 6 classes of enzymes mentioned in Lecture.