Bioorganic Chemistry

BIOORGANIC CHEMISTRY

PURPOSE OF COURSE

Bioorganic chemistry studies the chemistry of organic biomolecules. Itis a rapidly growinginterdisciplinary fieldthat combines organic chemistry and biochemistry. Please recall that organic chemistry investigates all molecules that contain carbon and hydrogen, and biochemistry focuses on the network of molecular pathways in the cell. Bioorganic chemistry employs organic chemistry to explain how enzymes catalyze the reactions of metabolic pathways, and why metabolites react the way they do. Bioorganic chemistry aims to expand organic-chemical research on structures, synthesis, and kinetics in a biological direction.

This one-semester course will cover several advanced chemistry topics and will discuss the chemistry behind biological processes. The course begins by introducing you to the mechanisms behind the most common biological chemical reactions (Unit 1). You will then take a closer look at the metabolic processes of biomolecules. You will apply your knowledge of the structural features of organic molecules to biomolecules (Unit 2). The next four units will cover the chemistry of metabolic processes in the cell: lipid metabolism (Unit 3), carbohydrate metabolism (Unit 4), amino acid metabolism (Unit 5), and nucleotide metabolism (Unit 6). The medical significance of the relevant deficiencies of these pathways will be discussed as well.

COURSE REQUIREMENTS

In order to take this course you must:

Have access to a computer.

Have continuous broadband Internet access.

Have the ability/permission to install plug-ins or software (e.g., Adobe Reader or Flash).

Have the ability to download and save files and documents to a computer.

Have the ability to open Microsoft files and documents (.doc, .ppt,

.xls, etc.).

Be competent in the English language.

Have read the Saylor Student Handbook.

Have completed the following courses: CHEM101: General Chemistry I, CHEM102: General Chemistry II, CHEM103: Organic Chemistry I, and CHEM104: Organic Chemistry II

COURSE INFORMATION

Welcome to CHEM204. Below, please find general information on this course and its requirements.

Course Designer: Marianna Pintér, PhD

Primary Resources: This course is composed of a range of different free, online materials. However, the course makes primary use of the following materials:

- Dr. Joyce Diwan’s Biochemistry of Metabolism

- Dr. Michael W. King’s The Medical Biochemistry Page

- Michigan State University: Dr. William Reusch’s Virtual Textbook of Organic Chemistry

- Salman Khan’s Khan Academy

Requirements for Completion: In order to complete this course, you will need to work through each unit and all of its assigned materials. Please pay special attention to Units 1 and 2, as these lay the groundwork for understanding the more advanced, exploratory material presented in the latter units. You will also need to complete:

- Subunit 1.1Assessments

- Subunit 1.5.4 Assessment

- Subunit 2.1.1 Assessment

- Subunit 2.1.2 Assessment

- Subunit 2.2.1 Assessment

- Subunit 2.4.1Assessment

- Subunit 2.4.2 Assessment

- Subunit 2.5.1 Assessment

- Subunit 2.5.2Assessment

- Subunit 2.6.1 Assessment

- Subunit 2.6.3 Assessment

- The Final Exam

Please note that you will only receive an official grade on your Final Exam. However, in order to adequately prepare for this exam, you will need to work through the problem sets within the above-listed assessments.

In order to pass this course, you will need to earn a 70% or higher on the Final Exam. Your score on the exam will be tabulated as soon as you complete it. If you do not pass the exam, you may take it again.

Time Commitment: This course should take you a total of approximately 139 hours to complete. Each unit includes a “time advisory” that lists the amount of time you are expected to spend on each subunit. It may be useful to take a look at these time advisories and determine how much time you have over the next few weeks to complete each unit and to then set goals for yourself. For example, Unit 1 should take you approximately 26.25 hours to complete. Perhaps you can sit down with your calendar and decide to complete subunit 1.1 (estimated at 4.5 hours) on Monday night; subunit 1.2 (estimated at 3.5 hours) on Tuesday night; subunits 1.3 and 1.4 (estimated at 4.5 hours) on Wednesday night; etc.

Tips/Suggestions:As noted in the “Course Requirements,” there are prerequisites for this course. It may be helpful to review CHEM103: Organic Chemistry I and CHEM104: Organic Chemistry II before you begin this course. If you find the discussion of the clinical significance of metabolism fascinating in this course, you might consider takingBIO305: Genetics.

Please make sure to take comprehensive notes as you work through each resource. These notes will serve as a useful review as you study for your Final Exam.

LEARNING OUTCOMES

Upon successful completion of this course, the student will be able to:

Identify and characterize lipids, carbohydrates, amino acids, and nucleic acids.

Recognize chiral organic molecules, and explain their biological significance.

Explain the process of electrophilic and nucleophilic reactions, redox reactions, and enzyme catalyzed reactions.

Define the role of coenzymes and allosteric regulators in enzyme catalyzed reactions.

Compare and link terpenoid and steroid biosynthesis.

Compare and contrast the biosynthesis and the break down of biomolecules in the cell.

Predict the products of substitution, elimination, condensation, and redox reactions.

Design enzyme catalyzed reactions that lead to high-energy compound products.

Explain why certain lipids and amino acids are essential while others are not.

Determine the significance of fermentation during anaerobic metabolism.

Explain why certain metabolic pathways are called “cycles.”

Explain what happens if a eukaryotic cell lacks oxalic acid, ribulose bisphosphate, or ornithine.

Compare and contrast the Citric Acid Cycle and the Calvin Cycle.

CONTENT OUTLINE

UNIT 1: common mechanisms in bioorganic chemistry

Time Advisory: This unit should take you approximately 24.5 hours to complete.

Subunit 1.1: 4.5 hours

Readings: 2.5 hours

Web Media: 1 hour

Assessment: 1 hour

Subunit 1.2: 4 hours

Sub-subunit 1.2.1: 0.5 hour

Sub-subunit 1.2.2: 3.5 hours

Subunit 1.3: 0.5 hour

Subunit 1.4: 2.5 hours

Subunit 1.5: 5 hours

Sub-subunit 1.5.1: 0.5 hour

Sub-subunit 1.5.2: 0.5 hour

Sub-subunit 1.5.3: 1 hour

Sub-subunit 1.5.4: 1.5 hours

Sub-subunit 1.5.5: 1.5 hours

Subunit 1.6: 3 hours

Subunit 1.7: 3 hours

Subunit 1.8: 1 hour

Subunit 1.9: 1 hour

The reaction mechanism is the step-by-step sequence of events in a chemical reaction. It includes breaking chemical bonds, describing transition state intermediates, and making chemical bonds. In this unit, you will start with an overview of the functional groups of organic molecules. Next, you will study the mechanisms of nucleophilic substitution, electrophilic addition, condensation, elimination, and redox reactions. The goal is to highlight the fact that these reactions go forward only if the reactants meet specific structural requirements.

Understanding the mechanisms of these reactions is necessary, because they revealthe potential ofcertain enzymes to speed up similar reactions. Knowledge of reaction mechanisms also provides a basis for the design of pharmaceutical compounds, which manipulate the yield of reactions, and has implications in the treatment of metabolic diseases.

Learning Outcomes:

Upon successful completion of this unit, the student will be able to:

Explain the processes of electrophilic and nucleophilic reactions.

Identify redox reactions.

Predict the products of substitution, elimination, condensation, and redox reactions.

1.1Functional Groups in Biological Chemistry

Reading: The Third Millennium Online: James Richard Fromm’s “The Concept of Functional Groups”

Link: The Third Millennium Online: James Richard Fromm’s “The Concept of FunctionalGroups” (HTML)

Instructions: Please click on the link above, and study this entire webpage, starting at the beginning and continuing until the end of the disulfide group section. The basic structural characteristics of the functional groups are summarized here. Alcohols, aldehydes, ketones, carboxylic acids, amines, mercaptans, and esters are the most commonly discussed bioorganic molecules in this course. While all sugars are alcohols, some of them are aldehydes (reducing sugars) and others are ketones. Aminoacids have both amino and carboxylic functional groups; glycerol and fatty acids in fats and phospholipids, as well as the monomers of DNA and RNA, are joined with ester bonds. The amino acid cysteine has a thiol group, which is essential for the stabilization of protein structures with disulfide bridges. Functional groups play an essential role in the active sites of enzymes as well (i.e. the thiol group in the active site of thiol proteases and asparagine in carboxypeptidase).

Reading and note-taking will take approximately 2 hours to complete.

Reading: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: Classification by Functional Group”

Link: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Classification by Functional Group” (HTML)

Instructions: Please click on the link above, and study the “Classification by Functional Group” section on this webpage. It summarizes the reactivity of the functional groups in table format. You may want to return to this table when learning about specific examples of these reactions in later units of this course.

This resource will take approximately 30 minutes to complete.

Web Media: Carnegie Mellon University’s “Modern Biology / Biochemistry Flash Tutorials”

Link: Carnegie Mellon University’s “Modern Biology / Biochemistry Flash Tutorials” (HTML)

Instructions: Please click on the link above to access this is a functional group tutorial. You will find a table on this page with the name and the structural formula of non-polar and polar functional groups in the “Functional Groups” column. The “Properties” column provides you with several options to choose from. When you click on an option, the corresponding examples in the “Functional Group” column will be highlighted (i.e. clicking on “non-polar” highlights the methyl and the phenyl groups in the table). Additionally, if you click on one of the properties, the last column will change from “Examples” to “About non-polar,” and you can read a brief description of the non-polar functional groups. Please take your time to carefully study the correlations between the properties, functional groups, and definitions in this tutorial.

Studying this resource will take approximately 1 hour to complete.

Assessment: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Identifying Functional Groups”

Link: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Identifying Functional Groups” (HTML)

Instructions: Please click on the link above, read the instructions at the top of the webpage, and complete the assessment to check how well you recognize functional groups. You can check whether your responses are corrector incorrect by clicking on the “Check Answer” button. Please complete the entire quiz before you hit the “View Answers” button to see the complete answer key. This is the first part of the functional groups problem set.

This assessment should take approximately 30 minutes to complete.

Assessment: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Identifying Functional Groups”

Link: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Identifying Functional Groups” (HTML)

Instructions: Please click on the link above, read the instructions at the top of the webpage, and complete the assessment to check how well you recognize functional groups. You can check whether your response is corrector incorrect by clicking on the “Check Answer” button. Please complete the entire quiz before you hit the “View Answers” button to see the complete answer key. This is the second part of the functional groups problem set.

This assessment should take approximately 30 minutes to complete.

1.2Acids, Bases, Electrophiles, and Nucleophiles

1.2.1Acidity and Basicity

Reading: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Acidity and Basicity”

Link: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Acidity and Basicity” (HTML)

Instructions: Pleaseclick on the link above, and study the “Acidity and Basicity” section on this webpage for a review of acidity and basicity.

This resource will take approximately 30 minutes to complete.

1.2.2Nucleophilicity and Basicity

Reading: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Nucleophilicity and Basicity”

Link: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Nucleophilicity and Basicity” (HTML)

Instructions: Please click on the link above, and study the “Nucleophilicity and Basicity Factors in Organic Reactions” and “Acid Base Catalysis” sections on this webpage. Pay particular attention to the definition of Nucleophilicity as well as the figures that show bonding of electrophilic and nucleophilic sites in reactant molecules.

This resource will take approximately 1 hour and 30 minutes to complete.

Lecture: Khan Academy’s “Nucleophilicity (Nucleophile Strength)”

Link: Khan Academy’s “Nucleophilicity (Nucleophile Strength)” (YouTube)

Instructions: Please click on the link above, and take notes as you watch this video lecture (14 minutes). The video explains nucleophilicity and how to predict nucleophile strength. Listen to the presentation carefully two or three times until you are able to explain what nucleophilicity is and how to predict nucleophile strength.

Viewing this lecture several times and pausing to take notes should take approximately 1 hour to complete.

Lecture: Khan Academy’s “Nucleophilicity vs. Basicity”

Link: Khan Academy’s “Nucleophilicity vs. Basicity” (YouTube)

Instructions: Please click on the link above, and take notes as you watch the video (13 minutes). Listen to the presentation carefully two or three times as needed until you are able to compare and contrast nucleophilicity and basicity yourself.

Viewing this lecture several times and pausing to take notes should take approximately 1 hour to complete.

1.3Mechanisms: Electrophilic Addition Reactions

Reading: Chemguide: Jim Clark’s “Electrophilic Addition”

Link: Chemguide: Jim Clark’s “Electrophilic Addition” (HTML)

Instructions: Please click on the link above, and study this webpage for a general overview of Electrophilic addition.

Reading and taking notes will take approximately 30 minutes to complete.

1.4Mechanisms: Nucleophilic Substitution Reactions

Reading: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Mechanisms of Nucleophilic Substitution Reactions”

Link: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Mechanisms of Nucleophilic Substitution Reactions” (YouTube)

Instructions: Please click on the link above, and study this entire webpage. Note the energy profile of nucleophilic substitutions. Take advantage of the animations that are linked to the SN1 and SN2 substitutions; to access these, press the “Click Here” buttons at the end of the SN1 Mechanism and SN2 Mechanism sections.

Studying this resource and note-taking will take approximately 2 hours and 30 minutes to complete.

1.5Mechanisms: Nucleophilic Carbonyl Addition Reactions

1.5.1Nucleophilic Addition Reactions

Reading: Chemguide: Jim Clark’s “The Reduction of Aldehydes and Ketones”

Link: Chemguide: Jim Clark’s “The Reduction of Aldehydes and Ketones” (HTML)

Instructions: Please click on the link above, and study this webpage to learn about the reduction of aldehydes and ketones.

This resource will take approximately 30 minutes to complete.

1.5.2Alcohol Formation

Reading: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Aldehydes & Ketones”

Link: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “Aldehydes & Ketones” (HTML)

Instructions: Please click on the link above, and study the “A. Hydration and Hemiacetal Formation” section on this page. Make sure to select “Click Here” at the end of the “Stable Hydrates and Hemiacetals”section, and study these examples. Note that hemiacetals and acetals form when simple sugars undergo a spontaneous rearrangement in an aqueous solution.

Studying this resource will take approximately 30 minutes to complete.

1.5.3Imine (Schiff Base) Formation

Reading: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “C. Formation of Imines and Related Compounds”

Link: Michigan State University: William Reusch’s Virtual Textbook of Organic Chemistry: “C. Formation of Imines and Related Compounds” (HTML)

Instructions: Please click on the link above, and study the “C. Formation of Imines and Related Compounds” section on this webpage. You may wish to click on any embedded hyperlinks to read about associated content. Clicking on the grey “Imine Formation” button opens a new window with an animation of the imine formation reaction. Also, selecting the “Click Here” link at the end of this section of text will take you to a webpage with examples of other carbonyl derivatives.

Studying this resource will take approximately 1 hour to complete.