Syllabus

Biochemistry, is an advanced overview of general biochemistry. A study of protein structure and their physical properties; how these properties relate to catalysis, regulation of catalysis and metabolic chemistry. with respect to their relationship to physiological conditions.

Instructor: Dr. David Jollie

General principles CLFS 690 is designed to teach some of the general principles of biochemistry while relating them back to the physiological conditions of an organism. There are several recurring topics designed into this course: Relationship of biochemistry to the physiology of an organism Relationship of bioenergetics to the physiological state Regulation of rates through the metabolic pathways Relationship of enzyme structure to catalysis and regulation. Description of the chemistry underlying most of the metabolic reactions Role of DNA, RNA and protein synthesis in the observed physiologic state Role of DNA in inheritance and genetic manipulation and gene therapy There are many examples of these principles throughout biochemistry and the number of well defined systems is growing at a rapid pace. There is not near enough time to give more than a representative number of examples in this course; yet, examples are amongst the best teaching tools. Accordingly, this course will center around articles obtained from the popular press such as, The Washington Post or New York Times. For instance, there are two recent articles in The Washington Post that deal with different aspects of blood clotting. To fully understand the process of blood coagulation one must understand the principle of protein structure, physical interaction between proteins, catalysis, regulation of catalysis, protein synthesis and energy metabolism. A look at the inherited diseases of blood coagulation allows an excursion into the relevant topics of genetic manipulation and gene therapy.

Course objectives: CLFS 690 is a one session course in general biochemistry designed for the Masters of Life Sciences Program. In this course the student is expected to develop:

(1) A foundation in the descriptions, chemistries and physical properties of proteins and enzymes.

(2) An understanding of the relationship of the structure of an enzyme to its function.

(3) A understanding of the central energy metabolism as well as the basic chemical properties that underlie these processes.

(4) An understanding of the mechanisms of regulation of metabolic processes

(5) The interdependent relationship between enzyme catalysis, metabolism, regulation and their importance to the physiological condition of an organism.

(6) An understanding of the process of inheritance and protein synthesis.

Textbook: McKee and McKee Biochemistry, An Introduction Wm. C. Brown Publishers (1996) Plus supplemental reading assigned throughout class from reviews and primary literature. The syllabus below is described by module; each module is expected to take about one week to complete Introduction: presentation of the articles upon which the following modules are based. Description of the general process upon which the articles depend. Principles that will need to be explained to understand the articles and the process. Examples presented in each module will be relevant to these articles.

Module 1 Amino acids and Proteins

Properties

• non polar
• polar
• ionizable

• Ionization of weak acids and bases
  • pK
  • ionization at given pH
• Protein structure
  • Primary structure
  • Secondary structure
    • helix
    • sheet
  • Tertiary structure
  • Quaternary structure
• Summary of covalent and non covalent forces that maintain structures

Module 2 Physical properties of proteins

• charge
• size
• hydrophobic
• methods for observing these properties
  • electrophoresis
  • electrophoresis with SDS and DTT E.
• Proteins
  • binding
    • structural
    • antibodies
    • transport
    • nucleotide binding
• Catalytic enzymes

Module 3 Thermodynamics vs. kinetics

• Reversibility of reactions
• Conservation of energy
• Standard conditions
• Thermodynamics
  • determines favored direction of reaction
  • determines possible extent of reaction
  • does not determine rate
• Kinetics
  • activation energy
  • height of activation energy barrier determines observed rate
  • catalysis lowers activation energy barrier

Module 4 Protein structure as it relates to function

• Mechanisms of catalysis

• Rate enhancement
• Substrate specificity
• Electrostatic interactions
• General acid and base catalysis
• Covalent intermediates

• Involvement of protein structure in these mechanisms
• Changes in structure alter the protein / enzyme properties.
• Things that alter proteins structure.

Module 5 General Chemistry of biochemistry

• Isomerization B. Hydrolysis C. Elimination
• Oxidation/reduction
• Aldol condensation/cleavage
• Thermodynamics of each
  • use and making of ATP
  • coupling hydrolysis of ATP to "reverse" reactions

Module 6 Regulation

• Different levels of regulation
  • protein synthesis/degradation
  • allosteric regulation
  • reversible covalent modification
  • proteolytic processing
• Each regulation level good for different reasons
• Requirements for ATP in synthesis and degradation cycle
• Reversibility of the different methods of regulation
• Consequences of misregulation

Module 7 Metabolic processes central to ATP synthesis

• glycolysis
  • ATP synthesis
  • No molecular oxygen required end product lactic acid
• Krebs Cycle

Module 8 Oxidative Phosphorylation

• redox reactions provide energy to drive ATP synthesis
• Requirement for molecular oxygen
• coupling a pH gradient to ATP synthesis
• the molecular machine required for ATP synthesis

Module 9 Central Dogma of biological systems

• DNA -> RNA -> protein
• DNA "self replicating" genetic material
• transcription of DNA to RNA
• translation of RNA to protein
  • ATP for each step in cycle
  • sequence dependence between DNA and protein
• DNA mutation yields different protein
• signals that lead a protein to be excreted from a cell

Module 10 Genetic manipulation

• inherited diseases

• DNA mutation 2. lead to protein misfunction

• Gene therapy

• need to deliver a new DNA sample
• which gene to deliver
• role of virus as delivery agent
• few successes and many failures

Grading Procedure:

• Weekly quiz covering the topic of the module. (30%)
• Involvement in a threaded discussion about topics from each module. (30%)
• A paper similar to the course itself. It should cover a reasonable explanation of some important aspects of a topic from some news article about a biological system. (40%)