LIPID SCIENCE AFNS 414 (Undergraduate Student Course Outline)

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LIPID SCIENCE AFNS 414 (Undergraduate Student Course Outline) Winter Semester 2008 University of Alberta Department of Agricultural, Food and Nutritional Science Instructor: Lecture: Office: E-mail: Dr. Randall J. Weselake Tuesday, Thursday; 12:30-1:50 p.m. B41 Computing Science Centre Room 520 - Agriculture/Forestry Centre randall.weselake@ualberta.ca Telephone: 492-4401 Pre-requisite: An introductory undergraduate course in biochemistry (e.g. Biochemistry 200 Introductory Biochemistry or Plant Science 331 Plant Biochemistry I) or consent of instructor General Information Lipid Science will deal with fundamentals in lipid biochemistry including theory and laboratory exercises in lipid analysis. In addition to completing term tests and a take-home exam, you will deliver a 30 min seminar and prepare an essay on the same topic as the seminar. A lot of the information will be provided in the form of lectures and through some discussion of references to the literature that are easily accessible online. The course will include guest presentations by other lipid researchers. Course Content I. Introduction to Lipid Science II. III. IV. Fatty Acids Characteristics of Other Lipids Lipid Extraction and Isolation of Lipid Classes V. Analysis of Fatty Acid Composition using Gas Chromatography VI. VII. VIII. IX. Mass Spectrometry of Lipids Analysis of Lipids using High Performance Liquid Chromatography Analysis of Positional Distribution of Fatty Acids Storage Lipid Metabolism X. Miscellaneous Topics in Lipid Science

Grade Composition Date Duration Value Quiz Feburary 5 th 30 minutes 10% Midterm Exam March 6 th 75 minutes 20% Laboratory Exercises 10% Essay 20% Seminar T.B.A. 30 minutes 10% Take Home Exam April 1 st -10 th 9 days 25% Class Participation 5% Total 100% The quiz will give you an idea of the style of questions that the instructor will ask on exams. The midterm exam and final take home exam will be comprehensive. The take home exam will be handed out in class on April 1st and is due by 4:30 p.m. on April 10 th. Implementation of University of Alberta Grading System: Throughout the term, raw marks will be assigned to reflect the performance on each component of the course. Letter grades will be assigned only to the final distribution of mark totals. Policy on Electronic Devices: Only approved non-programmable calculators are permitted during the quiz and midterm exam in class. Code of Student Behaviour Academic dishonesty is a serious offense and can result in suspension or expulsion from the University. All students at the University of Alberta are subject to the Code of Student Behaviour, as outlined at http://www.ualberta.ca/~unisecr/policy/sec30.html. Please familiarize yourself with this information and ensure that you do not participate in any inappropriate behavior as defined by the Code. Key components of the Code include the following statements. 30.3.2(1) Plagiarism: No Student shall submit the works, ideas, images or data of another person as the Student s own in any academic writing, essay, thesis, project, assignment, presentation or poster in a course or program of study. 30.3.2(2) No Student shall represent another s substantial editorial or compositional assistance on an assignment as the Student s own work. Please speak to the instructor if you have any questions or concerns about the Code, particularly as it pertains to team/group assignments, internet and library research, using the same work as part of assignments in more than one course and the definition of plagiarism.

LIPID SCIENCE AFNS 414/514 Seminar and Essay Information - Winter 2008 Seminar Each student will present a 30 minute seminar on a lipid science topic. There will be three seminars per lecture beginning later in the term (the schedule for seminar presentations will be supplied towards the end of January). Students should choose their seminar topic and submit it for approval by the instructor by January 24 th. The order of presentation will be assigned on February 5 th. Each speaker is to provide the instructor with a Preliminary Abstract (about 250 words; typed and double-spaced) of his/her presentation and Preliminary Reference List (5 references from papers published within the last 5 years) by March 4 th. The abstract should be a concise overview of the seminar. These references should be from papers that are easily accessible online. The abstracts and reference lists will be made accessible so that each person has the opportunity to do some research on the topics of the other speakers. Ten percent of the value of the preliminary abstract and reference list will be deducted for every day the document is late. The following factors will be taken into consideration when evaluating the presentations: Preliminary abstract and reference list 10 Content 10 Organization 10 Clarity of presentation 5 Familiarity with the topic 5 Use of visual aids 5 Points Timing 5 Essay Total 50 The essay, which has the same topic as the seminar, should be based on information from scientific journals. References to review articles should be avoided or kept to a minimum. The material should be presented in your own words. The essay should contain a table of contents, updated abstract, an introduction, a main body and a conclusion. The updated abstract (about 250 words) should be a concise overview of the essay. The introduction should explain the purpose of the essay and how the information will be organized.

2 The main body of the essay should be a carefully thought out and organized account of recent advances in the area. It is essential to read recent papers in the area and attempt to analyze and integrate the information of several papers. It may be helpful to sub-divide the main body into sections. The conclusion should summarize and emphasize the significance of what was discussed in the main body of the essay. Comment or speculate on possible future directions of the research. If figures and/or tables are used in the essay, avoid the cut and paste approach. Figures and tables should be creatively adapted from the original source. For example, a table can be prepared by integrating the information from several papers. Legends to figures and tables should be detailed enough so that the figures and tables can be understood. The essay should contain 20-30 references from scientific papers. At least 10 of these references should be papers published in the last 5 years. The "author-date" system should be used when positioning references in the text. Use the referencing procedure adopted by Biochemistry and Cell Biology. It may be useful to begin with some general reading on the topic by referring to relevant sections in textbooks (e.g. dealing with food science; animal nutrition and physiology). PubMed, Ingenta and other databases available on the Internet will be useful in locating relevant scientific articles and key researchers in the area. Avoid using Internet addresses, however, in your reference list. As a possible approach, you might focus on the recent work of a few research groups. The introduction, main body and conclusion of the essay will consist of 2,500-3,000 words (excluding illustrations, tables and references). The document should be typed and double-spaced. Please supply a word count on the last page of the essay. Remember to proofread your essay prior to submitting it. The essay is due in class on March 25 th. Ten percent of the value of the essay will be deducted for every day the document is late. The following factors will be taken into consideration when evaluating the essay: Content 30 Organization 10 Grammar, style & spelling 5 Points Referencing 5 Total 50 Further details regarding the assignments will be discussed in class.

Name Student LIPID SCIENCE AFNS 414/514 Quiz February 5, 2008 Value 10% Duration 30 min THIS QUIZ IS OUT OF 24 POINTS POINTS [4] 1. Draw a triacylglycerol containing the following fatty acyl moieties. -18:3cisΔ 9,12,15 22:5cisΔ 4,7,10,13,16,19 16:0 [6] 2. Rank the following acylglycerols in order of increasing solubility in water: a triacylglycerol, a diacylglycerol and a monoacylglycerol. All of these acylglycerols contain only 16:0 moieties. Please support your answer with a concise rationale.

2 POINTS [4] 3. Describe the difference between a split and a splitless injection for gas chromatography. What must you do in order to prevent excessive peak broadening with a splitless injection? [6] 4. How might you conclusively determine the position of a double bond in a highly unsaturated fatty acid by GC/MS? Which derivitization technique would you choose? What spectral characteristics would be diagnostic of a double bond in this case? [4] 5. What enzyme would you use for the stereospecific analysis of phosphatidylcholine? Explain why you chose this enzyme.

Name Student No. LIPID SCIENCE AFNS 414/514 Instructor: Dr. Randall Weselake, Rm. 520, Agriculture/Forestry Centre Midterm Exam March 6, 2008 Value 20% Duration 75 min THIS EXAM IS OUT OF 48 POINTS SECTION I. [12 POINTS] Provide brief explanations and/or structures (if required) for the following terms/phrases. Two points per explanation/structure. 1. thromboxane 2. Using a non-polar solvent system for lipid extraction, what physical property would you expect any contaminants to have? Give an example of a possible contaminant. 3. two aspects of peroxisomal -oxidation that differ from mitochondrial -oxidation 4. function of the glyoxylate cycle

2 5. precaution taken in the extraction of plant lipids 6. structure of 12-hydroxy cis-9-octadecenoic acid SECTION II. [36 POINTS] Provide answers to the following questions. Your answers must be supported with a rationale and calculations where appropriate. POINTS [2] 1. What is the difference between canola oil and rapeseed oil? [4] 2. Why is there a need for enoyl-coa isomerase for -oxidation of dietary unsaturated fatty acids?

3 POINTS [4] 3. Many of the enzymes of the -oxidation pathway have relatively broad specificities for fatty acyl chain lengths. Why is this important for the economy of the cell? [4] 4. Suppose a cell is deficient in phosphatidate phosphatase. What effects on lipid metabolism would you expect? [8] 5. A molecular species of triacyglycerol from an oil-forming insect from another solar system is composed of an eicosanoyl moiety, a docosanoyl moiety and an octanoyl moiety. Assuming that this insect can effectively hydrolyze this triacylglycerol and that the insect s -oxidation system is similar to ours, determine the number of FADH 2 molecules produced via -oxidation from two molecules of this triacylglycerol species.

4 POINTS [8] 6. You are working with a yeast mutant that is deficient in triacylglycerol synthesis. You hypothesize that the yeast cannot accumulate TAG because one or more of the Kennedy pathway enzymes has been knocked out. You decide to undertake a detailed analysis of lipid classes to determine whether the yeast is able to produce other glycerolipids, in hopes of identifying which of the enzymes might have been affected. a. You have extracted total lipids from a sample of the yeast culture. What technique might you use to isolate various glycerolipids from the total lipid extract? b. Suppose you found that the yeast mutant was able to produce lysophosphatidic acid, phosphatidic acid, and diacylglycerol, but not triacylglycerol. Based on this information, which enzyme has likely been knocked out? Support your answer with a diagram of the Kennedy pathway.

5 [6] 7. Your best friend has received some GC/MS data from a collaborator. Unfortunately, there was a mix-up with the sample names, and your friend, who has not taken Lipid Science, is not sure how to interpret the data. They can tell you for certain that one of the samples is saturated, and the other is monounsaturated. Some potentially useful ions have been identified, but your friend doesn t know what they mean and hopes you can help. a. What type of derivative is shown in the mass spectra below? How can you tell? b. Clearly identify which sample is monounsaturated. How can you tell? c. Do these two fatty acids have the same carbon chain length? How can you tell?

6

LIPID SCIENCE AFNS 514 Take-home Exam April 2007 Value 25% Due date: April 12, 2007 at 4:30pm (Room 5-18 Ag/For) THIS EXAM IS OUT OF 60 POINTS. Please submit a typed, double-spaced (12pt font) response for each question. Cite relevant references where appropriate. 1. (15 marks, max 1 page) Enova and Olestra are two fat substitutes that have been promoted as low-calorie alternatives to traditional fats and oils. a) Compare and contrast the structural characteristics and metabolic fates of these products compared to normal dietary fat. (5 marks) b) How might you prepare the active ingredient in Enova? (5 marks) c) How could you confirm that only one form of the active ingredient in Enova is present in your preparation? (5 marks) 2. (15 marks, max 1 page) Several drugs have been developed for the treatment of obesity in humans, and more recently, dogs. None of the current therapies, however, target triacylglycerol (TAG) synthesis directly, which would seem to be a logical target for combating obesity. a) Based on what you know of lipid metabolism in animals, identify possible therapeutic targets whose inhibition could result in decreased TAG synthesis. Provide a rationale for choosing or excluding the various enzymes involved in TAG synthesis. (10 marks) b) Are there any published reports of inhibitors targeting your chosen enzyme(s)? Why have these not been extensively employed thus far in the treatment of obesity? (5 marks)

2 3. (30 marks, max 2 pages, table not included) You are working on a project aimed at producing very long chain polyunsaturated fatty acids (C20-C22 PUFA) in plants. You introduce three enzymatic steps to constitute the pathway, and detect moderate levels of C20 PUFA and only trace levels of C22 PUFA in the seed oil of transformed plants. Although you are able to confirm that all three of your introduced enzymes are active, further analysis shows that neither C20 nor C22 PUFA accumulate to a great extent in the acyl-coa pool of developing seeds. a) Starting from either linoleic or α-linolenic acid, what are the three minimum enzymatic steps required to produce trienoic and tetraenoic C20/C22 fatty acids? (5 marks) b) Explain why the absence of C20 PUFA in the acyl-coa pool might impair elongation to C22 PUFA. (5 marks) c) Using your knowledge of lipid biochemistry, devise a strategy for increasing levels of C20 PUFA in the acyl-coa pool. (10 marks) d) The following positional analysis data were obtained from a transformed plant. Complete the following table. Provide one detailed example calculation. (10 marks)

3 Fatty acid TAG (%) LPC (%) 2-MAG (%) calc. sn- 3 14:0 0.13 0.57 0.00 16:0 5.49 12.89 0.84 16:1n-7 0.23 0.98 0.29 18:0 3.91 9.41 0.50 18:1n-9 20.01 21.72 19.79 18:1n-7 2.08 3.04 0.60 18:2 n-9 0.47 0.00 1.14 18:2n-6 16.06 16.79 17.59 18:3n-6 28.01 8.20 39.41 18:3n-3 2.98 4.03 2.14 18:4n-3 1.90 2.31 2.41 20:0 0.65 0.70 1.13 20:1n-9 1.39 2.71 0.00 20:2n-6 1.36 0.77 1.49 20:3n-6 1.64 2.69 0.79 20:4n-6 3.73 2.20 3.86 20:3n-3 0.53 1.23 0.00 20:4n-3 0.94 0.00 0.69 20:5n-3 7.53 7.82 7.11 22:0 0.00 0.00 0.00 22:1n- 11 0.00 0.00 0.00 22:1n-9 0.00 0.00 0.00 22:4n-6 0.00 0.00 0.00 22:5n-6 0.00 0.00 0.00 22:5n-3 0.21 0.48 0.00 24:0 0.32 0.44 0.00 22:6n-3 0.43 1.03 0.24 24:1n-9 0.00 0.00 0.00