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HUMAN BIOCHEMISTRY BCHM2072 and BCHM2972 SEMESTER 2, 2006 Overview of the two Units of Study BCHM2072 is a 6-credit point course which consists of 26 lectures (two per week) and six five-hour practical sessions (one per fortnight). The major aim of the lecture course is to provide an introduction to metabolism and cell biology and, in particular, to the way that metabolic processes are integrated between the tissues of our body. The major function of the practical course is to nurture the technical and generic skills introduced in MBLG1001 (and, perhaps, BCHM2072 and MBLG2071) and to introduce some new experiences: eg. working with radioactivity, preparing oral presentations, and designing assay systems. BCHM2972 is the Advanced version of the above course. The topics presented are generally the same but, for six lectures, the BCHM2972 will treat certain concepts at a more greater depth (eg, at a more mechanistic level). Advanced students will perform some extension tasks in the practical classes and will have a different examination paper. How to qualify for the courses To qualify for BCHM2072 you must obtain a full pass (>50%) in the first year course, MBLG1001 (or its pre-2005 equivalent) or MBLG2071. Many of the practical experiments performed this semeseter are contingent on you being able to handle basic lab equipment and perform rudimentary biochemical calculations (ie, all the things tested in the MBLG skills tests). To qualify for BCHM2972 you need distinctions in one of the previous MBLG/BCHM units of study AND distinctions in Junior Chemistry. However, let us know if you feel that you would like to be considered for entry with lower qualifications. BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 1 Lectures The lectures will be in Chemistry Lecture Theatre 1 at 10 am every Wednesday and Friday of the Semester. Every ODD Friday (starting Week 3), the Advanced class goes to Room 471 in the Biochemistry Building. Lecturers Your lecturers for this semester are : A/Prof Gareth Denyer (Room 715, Ph 9351 3466, [email protected]) Dr Simon Easterbrook Smith (Room 605, Ph. 9351 3905, [email protected]) Vanessa Gysbers (Room 711, Ph 9356 5352 [email protected]) All the lecturers are available throughout the semester for consultation. Although it is acceptable to call on them at any time, it would be wiser to phone or email them to arrange an appointment. It is important to remember that the examination questions relating to specific topics will be set by the lecturers who delivered the relevant lectures. Therefore, if you experience any difficulties with any part of the lecture course, discuss the matter first with the person who gave the lectures. For other problems and inquiries, contact the Course Coordinator, A/Prof Gareth Denyer. Lecture Topics An overview of the lectures in this course is given below. A more detailed description of the content of each lecture will be put on the BCHM2072 web page as the course progresses. Be warned that the precise content and emphasis of each lecture may vary slightly from that described below. It is essential that you revise from a full set of lecture notes, NOT just this syllabus. Similary, the timetable is meant as a general guide to the order of material covered. Some topics may require more time than that allocated in this table while other topics may take less. USE THIS LIST AS A GUIDE ONLY! BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 2 ENERGY BALANCE (Weeks 1 - 3) Introduction to metabolism Anabolism and Catabolism Linkage of synthesis and degradation through ATP and NADH General facts regarding ATP Overview of Catabolism General structure of fuel molecules: fats and carbohydrates Strategies of energy extraction: fuel transport, cytoplasmic trapping, use of carriers, hydrogen stripping, generation of proton gradients and the sythesis of ATP. Coupling. Inderdependence of electron transport and oxidative phosphorylation. Relationship between energy expenditure and fuel oxidation An amusing role play to illustrate coupling. Inhibitors of ATP generation. Uncoupling fuel oxidation from ATP synthesis. Dinitrophenol and uncoupling proteins. Development of anti-obesity drugs and nature's radiator: brown adipose tissue. The molecular machinery of fuel oxidation and ATP synthesis Details of the electron transporters (NAD, FAD) and the structure of the electron transport chain. Electron transporting complexes and the movement of electrons between and within them. The mechanism of proton pumping. The structure and function of the F1F0ATPase Stoichometry of ATP sythesis. Whole body energy balance Measurement of whole body energy expenditure Regulation of metabolic rate The balance between energy intake and energy expenditure BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 3 CARBOHYDRATES (Weeks 4 - 6) Carbohydrate sources , digestion and tissue uptake Basic overview of carbohydrate structure Simple sugars (eg, glucose and fructose), disaccharides (maltose, lactose and sucrose) and polysaccharides (amylose, amylopectin) Dietary sources, digestion and absorbtion Introduction to blood glucose homeostasis: keeping blood [glucose] at 5 mM The Glycemic Index Glucose disposal: Glucose transport into tissues. GLUTs. Tissue differences. Trapping of glucose inside the cell. Carbohydrate chemistry. Nomenclature: chain lengths, aldose/ketose, formation of rings/open chains, numbering, stereochemistry (D/L forms), anomeric forms Drawing carbohydrate structures Sugar tests: reducing sugars. Formation of disaccharides: glycosidic bonds. Polysaccharides: tertiary structure of cellulose and starch Fates of glucose – Glycogen Overview of glycolysis, glycogenesis, lipogenesis and pentose phosphate pathway. Importance of rate limiting enzymes in determining fate of G6P. Properties of flux generating steps. Hormonal stimulus for glucose transport and glycogenesis complemented by energy charge stimulus for glycolysis. Details of regulation of glycogen synthase and molecular mechnanism of glycogenic pathway. Liver/Muscle differences in glycogen synthesis. Glucokinase vs Hexokinase Fate of fructose. BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 4 Fates of glucose - Lipogenesis Generation of acetyl CoA and hormonal activation of pyruvate dehydrogenase activation of acetyl CoA carboxylase for formation of malonyl CoA Hormonal and metabolic regulation of acetyl CoA carboxylase Fatty acyl synthase - detailed mechanism Formation of triglyceride: source of glycerol transport of acetyl CoA into the cytoplasm: ATP-citrate lyase and inhibtors Generation of reductant (NADPH) by pentose phosphate pathway Desatruation of fatty acids. FAT and PROTEIN (Week 6-7) Dietary Fat: sources, digestion and transport Fat digestion: bile salts, micelle formation, lipases Fat substitutes and lipase inhibitors Chylomicrons - Structure of lipoproteins - transport of fat to the tissues via lymphatic system Uptake of fat into tissues: lipoprotein lipase. Reesterification of fatty acids and glycerol for fat storage Cholesterol metabolism Cholesterol absorbtion. Cholesterol transport: chylomicron remnants, VLDL, LDL LDL receptors: consequences of defect. HDL: reverse cholesterol transport Strategies for lowering blood [cholesterol] Protein metabolism Protein intake. Essential vs non-essential amino acids. Consequences of inadequate intake. Transamination and processing of carbon skeletons Phenylketouria Funneling of nitrogen to liver for nitrogen excretion and Urea synthesis BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 5 CELL SIGNALING (Weeks 8 -9) Protein Trafficking Biosynthesis of extra-cellular proteins; roles of signal peptides, SRP and the translocon Folding, quality control and glycosylation of proteins in the ER Intrinsic and peripheral membrane proteins, protein and lipid anchors Processing cellular messages Overview of signal transduction: autocrine, paracrine, endocrine and contact signalling signal delivery by protein kinases and phospholipases, adaptor proteins, cross-talk and divergence between pathways Types of receptors: 7-TMS receptors, protein tyrosine kinase (PTK) receptors, cytokine receptors, ligand-gated ion channels. Messaging systems Coupling of the JAK/STAT pathway to cytokine receptors; roles of PTKs and SH2 domains Activation of the MAP kinase cascade by growth factor receptors; adaptor proteins, roles of SH2 and SH3 domains. Phospholipase C and signal transduction; production of IP3 and DAG, mobilization of Ca2+, activation of protein kinase C. Role of protein kinase C in activation of NFKB. Mechanism of nuclear import of NFKB. G protein-coupled receptors; roles of G proteins. Activation of adenyl cyclase and protein kinase A. Pathological consequences; cholera toxin.. Short-term and long-term effects of protein kinase A; effects on glycogen metabolism, activation of CREB BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 6 STARVATION (Weeks 10-11) Starvation - The Post-absorbtive period Tissue requirements vs fuel stores. Special focus on brain requirements. Mobiliisation of liver glycogen Activation of liver phosphorylase by glucagon - control by reversible phosphorylation cAMP and protein kinase amplification cascade Starvation - The first 48 hours Lipolysis from adipose tissue: role of PKA and phosphodiesterase Use of fatty acids by muscle. Introduction to the beta-oxidation pathway. Generation of acetyl CoA and the inhibition of pyruvate dehydogenase The Glucose-Fatty Acid cycle and glucose conservation Starvation - Extended Delivery of amino acid skeletons. Proteolysis and deamination. The glucose accounting sheet. Need for ketogenesis. Use of ketone bodies by tissues The steady state of long term starvation Starvation - Details of the Key Pathways The mechanism of beta-oxidation. Oxidation of unsaturated fatty acids. Mechanism of ketone body production. The gluconeogenic pathway. Key enzymes, substrates and control BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 7 EXERCISE (Week 12) Exercise - Light exercise to moderate exercise Muscle fibre types: muscle role of Ca2+ and ATP Provision of ATP by oxidative phosphorylation Fuel selection during walking: gradual dominance of fatty acid oxidation Running - increasing the rate of the Krebs cycle, electron transport and oxidative phosphorylation. The biochemistry of the Krebs Cycle. Exercise - competitive intensitiy More intense exercise. Glycogenolysis in muscle. Importance of glycogen during intense exercise. Glycogen supercompensation. Strategies for glycogen sparing and glucose conseveration Ergogenic aids for the marathon runner. Exercise - sprinting Glycolysis and its regulation Energy charge, Creatine phosphate Lactate and acid accumulation Ergogenic aids for the sprinter DIABETES (Week 13) Juvenile Onset Diabetes Mellitus Symptoms of Type I Diabetes Metabolic consequences of hypoinsulininemia Overview of cause of IDDM Treatment of IDDM. Long term complications of diabetes Maturity Onset Diabetes Mellitus Insulin resistance: definition and measurement; The Euglycemic Clamp. Defective insulin secretion Treatment of NIDDM. BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 8 TIMETABLE Week Beginning Wednesday Friday 1 24th July Introduction Energy Balance 2 31st July Energy Balance Energy Balance th 3 7 Aug Energy Balance Energy Balance * 4 14th Aug 5 Carbohydrate Carbohydrate st Carbohydrate Carbohydrate * th 21 Aug 6 28 Aug Carbohydrate Fat 7 4th Sept Fat Protein * th 8 11 Sept Cell Signaling Cell Signaling 9 18th Sept Cell Signaling Cell Signaling * Break 25th Sept Holiday Holiday nd 10 2 Oct Starvation Starvation 11 9th Oct Starvation Starvation* 12 th Exercise Exercise* rd Diabetes Diabetes* 13 16 Oct 23 Oct An asterix shows the planned dates of the Advanced lectures. However, the exact sessions on which the BCHM2072 and BCHM2072 students will have different classes may change nearer the date. Text Books It is assumed that you have purchased a recent edition of a general Biochemistry text by now. Indeed, any up-to-date Biochemistry text-book will give fundamental coverage of metabolism and will be reasonably sufficient for this course – especially as materials will be provided during the semester. However, your recommended text-book for this semester is Voet, Voet and Pratt Fundamentals of Biochemistry: Life at the Molecular Level, 2nd edition. Although we do not lecture ‘from’ this book, we will try and refer to it as much as possible.. An additional benefit to buying the book is that it gives you access to the web site that accompanies the book. The web site contains many animations, diagrams, practice questions, study aids, etc, etc. BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 9 Internet Resources The Human Biochemistry web page is at: http://www.mmb.usyd.edu.au Follow the links to Student Information > Current Students > BCHM2072. This site will be updated regularly as the course progresses. Please note, though, that the laboratory printers are NOT to be used for printing out WWW files. Any abuse of this will be reported to A/Prof Denyer! Scary hey! THE PRACTICAL COURSE. General Arrangements The practicals are not specifically designed to complement the material taught in lectures but are mainly designed to teach you a wide range of scientific and generic skills (ie, the sorts of skills much loved by employers). Laboratory classes run from 1.00 pm to 6.00 pm Tuesday to Friday. Students have been allocated practical groups using information provided by Student Records. Practical classes are done on a FORTNIGHTLY cycle – and you will be allocated to either an ODD or EVEN cycle. There will be no practical classes in the first week of the semester. HOORAY!!! Thus you will do your pracs in either weeks 2, 4, 6, 8, 10 & 12 or in Weeks 3, 5, 7, 9, 11 and 13. You may have the same demonstrator as in MBLG1001/2071 or BCHM2072 although we endeavour to minimise this. If you feel disadvantaged by having the same demonstrator twice see A/Prof Denyer. How do I change my practical day? If you will not be able to attend on your allocated practical day, you must notify us well BEFORE your first practical session (ie, early in Week 1). You MAY be allowed to switch days but you must provide reasons for wanting to change IN WRITING. YOU MUST NOT TAKE IT UPON YOURSELF TO CHANGE PRACTICAL GROUPS. Group change requests must be channelled through EMAIL to A/Prof Denyer. Students must cite their SID, old day/cycle, preferred new day/cycle and reasons for wanting to change. BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 10 When can I use the Computer Facility? There are 20 Macintosh computers in the laboratory. You may use the computer facility on any day from 9.30 am - 5 pm. Computers may ONLY be used for Biochemistry-specific work. In particular, the printers must NOT be used to print out any material that is not directly connected with your practical class. Students undertaking a practical have priority during class times. What happens if I miss some Practical Classes? As with previous MBLG and BCHM courses, you MUST attend >90% of practical classes, even with medical certification. This means that if you miss more than one class, you cannot expect to pass the practical course. It is, however, possible to make up classes and this can be arranged with A/Prof Denyer or the lab class supervisor. DO NOT TAKE IT UPON YOURSELF TO OMIT AND/OR ENTER SPECIFIC SESSIONS. You must get permission in writing to attend make-up classes. Where do I get a Practical Manual? The resource manual for the course is available from the University Co-op Bookshop (near the Noel Martin Recreation Centre) at a cost of about $20. . You will require this by the first practical class ie. Week 2 or 3. What else do I need? You should attend your first practical class with your own copy of the lab manual, a laboratory coat, a hard bound laboratory notebook and a waterproof marking pen. What if I need help with some part of the practical course? Your first port of call should be your demonstrator or, if they are not available, A/Prof Denyer. BE VERY SURE to read the section in your MBLG1001 Resource Manual on Laboratory SAFETY. Attendance in the labs is conditional on your doing this. Since you must have done MBLG1001 to enter this course, the information is not duplicated here. However, if you do not have a copy, please ask A/Prof Denyer. BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 11 ASSESSMENT This School supports and adheres to the Academic Board and Faculty of Science recommendations regarding the award of merit grades. Therefore, ALL marks are RAW until your final grade is ratified by the Faculty. In other words, marks for any component can be scaled up or down at Departmental and/or Faculty Examiners meetings. The lecture (theory) component of the course is worth 50% of the final assessment with the practical components contributing 50% to the final mark. However, a pass in both sections is essential. The lecture (theory) component of the course will be assessed by two hours worth of questions in the end of semester exam The practical component of the course will be assessed a) by your laboratory work (including your lab notebook, presentations, and assay design assignments) with the exact contribution of these individual components being detailed in the practical resource manual. However, in total, ‘practical work comprises 50% of the final practical mark. b) One hours worth of questions in the end of semester exam. The questions will be based on concepts, calculations and techniques covered in the labs. This will contribute 50% to the final practical mark. ACADEMIC HONESTY Any submitted reports that appear to have been copied or otherwise plagiarised may be seen as evidence of academic misconduct and may be subject to an investigation by the University Registrar. Further information on the Academic Policy of the University of Sydney is available on the university website (http://www.usyd.edu.au/ab/policies/). Of particular relevance here is the document entitled “Academic Honesty in Coursework (plagiarism)”. BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 12 SPECIAL CONSIDERATION It is Faculty of Science policy that there are no Supplementary Examinations for courses which are only studied for one semester. However, we recognise that sickness or other misadventures can have an adverse effect on your performance. Therefore, we have set up the following procedures to ensure that you are not disadvantaged because of illness or other problems. A copy of the Illness and Misadventure Policy for the School of Molecular and Microbial Biosciences is located on the School website. What you should do if you are sick (or have other problems) DURING the semester. Applying for special consideration 1. The student obtains an Application for Special Consideration form from the Student Information Office of the Faculty of Science, or from the Faculty website at www.science.usyd.edu.au, or from the School of Molecular and Microbial Biosciences website. 2. The student lodges the original of the application form and originals of any supporting documentation at the FACULTY Student Information office. Where it is not possible to obtain original documentations (for example, death certificate or police report), submission of a certified copy will be permitted. All other forms submitted must be originals, including the Professional Practitioners Certificate (PPC). Please note that it is also necessary to provide a copy of the application and all documentation for each unit of study in which consideration is being sought, to be certified by the Faculty and forwarded by the student to the School for assessment (ie, if you are applying for consideration for three units of study, you must submit the original documentation plus three copies). The Student Information Office will not make copies of any documentation submitted. For consideration due to serious illness a student must have a registered medical practitioner or counsellor complete the PPC, which is attached to the application form. A Medical Certificate is also acceptable provided that it contains information similar to that requested on the PPC (that is, it must provide information attesting to the severity of the illness and its impact on academic performance). For consideration due to misadventure, a PPC or other form of appropriate documentation is required which indicates the likely duration and effect of the misadventure on the student’s performance. BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 13 Please note that only the supporting documents provided at the time of initial application for Special Consideration will be used to assess the request. It will not be possible to submit further documentation relating to an initial application once an application has been lodged with the Student Information Office. Only those circumstances brought to the attention of staff at the time of lodgement will be taken into consideration when formulating an academic judgment. 3. The Student Information Office checks the application at the time of lodgement to ensure that a student’s documentation is adequate and, if so, will sign/stamp both the original application form as well as the student’s copies to confirm lodgement of the application at the office. The Student Information Office will enter the details contained on the application form into the Special Consideration database, which will be used to monitor the progress of the application. 4. The student takes the stamped and dated application form and documentation to the relevant School Administration Office for assessment. Please note that this must be done for each Unit of Study for which consideration is being sought. 5. When an academic judgement has been entered into the Special Consideration database, the Faculty will communicate the decision to the student via an e-mail to the student’s University e-mail address. It is expected that a response will be received by the student within seven days of initial application. What you should do if you miss an EXAM because of sickness or misadventure. If you are unable to sit an end-of-semester exam, you must apply for Special Consideration following the procedure outlined above, including submission of appropriate supporting documentation, within seven days from the date of the exam. If a student does not sit an examination and is not granted Special Consideration, a grade of AF (Absent Fail) will result for that examination. Special Consideration forms should be lodged with the Student Support staff on level 4 of the Biochemistry and Microbiology Building. BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 14 If you are granted Special Consideration, you may be permitted to sit for a postponed examination. It will be held during the week after the regular examination period. Although this exam will cover the same lecture and practical material as the original exam, it will contain new questions and may be in a different format. It will MOST ASSUREDLY NOT BE THE SAME EXAM. Let’s say that again, shall we….. IT WILL NOT BE THE SAME EXAM. There will be no further testing after this date. SIDs of those students eligible to sit this deferred exam will be posted on the School of Molecular and Microbial Biosciences website. IT IS YOUR RESPONSIBILITY TO FIND OUT IF YOU ARE ELIGIBLE TO SIT THE DEFERRED EXAM. Please note that the marks that you get for any exam that you sit will be treated as final marks. Good luck and have a good semester! BCHM2072/2972 Human Biochemistry Semester 2, 2006 Page 15