BBSG 501 Section 4 Metabolic Fuels, Energy and Order Fall 2003 Semester

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BBSG 501 Section 4 Metabolic Fuels, Energy and Order Fall 2003 Semester Section Director: Dave Ford, Ph.D. Office: MS 141: ext. 8129: e-mail: fordda@slu.edu Lecturers: Michael Moxley, Ph.D. Office: MS 1 st Floor: ext. 8190: e-mail: moxleyma@slu.edu Peggy Weidman, Ph.D. Office: MS 1 st Floor: ext. 8179: e-mail: weidmanp@slu.edu Carmine Coscia, Ph.D. Office: MS Rm. 121: ext. 8160: e-mail: cosciacc@slu.edu John Corbett, Ph.D. Office: MS Rm. 105: ext. 8165: e-mail: corbettj@slu.edu

Dr. Michael Moxley Lectures 1-4 (Basics of pathways are in Zubay handouts will show research examples) Date: 11/13/03 Lecture 1: Hexose Metabolism I Regulation of Glycolysis and Gluconeogenesis Resource Material: Biochemistry 4 th Edition, by G. L. Zubay: Chapter 14 293-323 and handouts Overview of Glycolysis and Gluconeogenesis Regulatory Enzymes Role of Phosphofructokinase 2 Tissue Specificity of Regulatory Enzymes Date: 11/14/03 Lecture 2: Hexose Metabolism II Regulation of Glycogenesis and Glycogenolysis Resource Material: Biochemistry 4 th Edition, by G. L. Zubay: Chapter 14 293-323 and hnadouts Overview of Glycogenesis and Glycogenolysis Enyzmes in the Regulation of Glycogen Metabolism Priming of Glycogen Synthesis Role of Glycogenin Tissue Isoforms of Glycogenin? Date: 11/17/03 Lecture 3: TCA Cycle Resource Material: Biochemistry 4 th Edition, by G. L. Zubay: Chapter 15, 324-345 and handouts Overview of Tricarboxylic Acid Cycle Regulation of the TCA Cycle Glyoxylate Cycle Anabolic Variant of the TCA Cycle Isocitrate Dehydrogenase Regulation of Substrate Utilization Differs in Prokaryotes and Eukaryote

Date: 11/18/03 Lecture 4: Regulation of Intemediary Metabolism in Different Tissues Resource Material:Class Handouts Regulation of Carbohydrate Metabolism in Cardiac and Skeletal Muscle Regulation of Carbohydrate Metabolism in Adipose Tissue Regulation of Carbohydrate Metabolism in Liver Dr. Peggy Weidman (lectures 5-10) Text book for these lectures: Molecular Biology of the Cell, Alberts, et al. Eds, 4th Edition, 2002,Garland Publishing, (HS Library has 3 copies of this book on reserve) DATE: 11/19/03 Lecture 5: Oxidative Phosphorylation I MBC, Chapter 14, pp. 773-775 and pp. 782-791 Three stages of respiration and overview of oxidative phosphorylation Linked redox reactions and respiratory electron transport respiratory electron carrier complex coupling of electron transport to proton pumping Date: 11/20/03 Lecture 6: Oxidative Phosphorylation II MBC, Chapter 14, pp. 775-781 the proton electrochemical gradient Rotary catalysis mechanism of ATP-synthase Coupling proton entry to ATP synthesis coupling of respiratory electron transport and ATP synthesis Regulation of Oxidative Phosphorylation

Date: 11/21/03 Lecture 7: Profits and Perils of Life in an Oxidizing Environment (reading to be provided) Mitochondrial diseases Other enzymes that use molecular oxygen Cytochromes P450 and detoxification of Xenobiotics Reactive oxygen intermediates and cellular defense mechanisms Generation of heat by uncoupler proteins Date: 11/24/03 Lecture 8: Overview of the ER MBC, Chapter 12, pp 698-710. Signal-mediated translocation into the ER Addition of core N-linked oligosaccaride ER Chaperones and protein folding Degradation of misfolded proteins The ER unfolded protein response Date: 11/25/03 Lecture 9: Protein Processing, Sorting, and Transport on the Secretory Pathway MBC Chapter 13, pp 711-738, Chapter 19, pp 1091-1096, Processing of core N-linked oligosaccarides in the Golgi Synthesis of O-linked carbohydrates, glycolipids, glycosaminoglycans proteolytic processing of prohormones, proenzymes, peptide neurotransmitters protein sorting and vesicular transport on the secretory pathway739 mechanisms for retention of ER and Golgi resident proteins Date: 12/1/03 Lecture 10: Overview of Endocytosis MBC Chapter 13, pp739-765 Regulated and constitutive secretion Sorting of lysosomal enzymes Pathways from the cell surface to the lysosome receptor-mediated endocytosis and clathrin-coated vesicles sorting and transcytosis in polarized cells Lectures 11-15: AMINO ACID AND ISOPRENOID METABOLISM Dr. C. J. Coscia

Reference Material for Lectures 11-15: Biochemistry, G. Zubay, 4th Ed. WM. C. Brown Publishers, 1998, Dubuque, Iowa Lecture 11 DATE: 12/2/03 Lecture: General Amino Acid Metabolism Required reading: Zubay, pp. 240-243 and pp. 597-602 Dynamic State of Nitrogen Metabolism Role of Transamination in Amino Acid Metabolism Lecture 12 DATE: 12/3/03 Lecture: Regulation of Nitrogen Excretion Required reading: Zubay, pp. 602-606 The Urea Cycle Renal NH3 Disposal Lecture 13 DATE: 12/4/03 Lecture: Regulation of Aromatic Amino Acid and One-Carbon Metabolism Required reading: Zubay, pp. 251-255 and pp. 710-712 Regulation of Aromatic Amino Acid Metabolism; Anabolic and Catabolic Pathways Folic Acid and One-Carbon Metabolism Biological Methylation and its Regulation Lecture 14 DATE: 12/5/03 Lecture: Regulation of Nucleotide Metabolism Required reading: Zubay, pp. 631-644, 655, 657 De novo Synthesis of Purine Nucleotides De novo Synthesis of Pyrimidine Nucleotides Nucleotide Interconversions

Lecture 15 DATE: 12/8/03 Lecture: Regulation of Isoprenoid Metabolism (Coscia) Required reading: Zubay, pp. 532-542, 548-550 Structural and Functional Diversity of Isoprenoids Mechanisms of Regulation of Cholesterol Biosynthesis DATE: 12/9/03 Lecturer: John Corbett, Ph.D. Lecture 16: L-arginine dependent NO synthesis pathway (Corbett) enos and regulation of vascular tone Role of inos in inflammation and immune Surveillance nnos, role of NO in neuronal signaling DATE: 12/10/03 Lecture 17 Regulation of triglyceride and cholesterol absorption and transport Resource Material: Biochemistry 4 th Edition, by G. L. Zubay: pp.480-482 and Chapter 23 Lipids: Definition, Classification and Structures Regulation of triglyceride digestion and storage mediated by bile salts, pancreatic lipase, lipoprotein lipase (LPL) Regulation of cholesterol and triglyceride transport by lipoproteins Regulation of cholesterol uptake by LDL receptors Atherosclerosis DATE: 12/11/03 Lecture 18 Regulation of the synthesis, degradation and trafficking of fatty acids Resource Material: Biochemistry 4 th Edition, by G. L. Zubay: Chapter 21 Hormonal regulation of triglyceride catabolism and synthesis Regulation of the transport of fatty acids as acyl CoA and acyl carnitine Regulation of fatty acid oxidation by mitochondrial and peroxisomal β-oxidation as well as α- and ω-oxidation Regulation of fatty acid synthesis by fatty acid synthase and acetyl carboxylase

Regulation of intracellular fatty acid uptake/utilization DATE: 12/12/03 Lecture 19 Regulation of phospholipid and sphingolipid synthesis Resource Material: Biochemistry 4 th Edition, by G. L. Zubay: Chapter 22 Biosynthetic pathways for the phospholipids and sphingolipids. Regulation of phospholipid and neutral lipid biosynthesis Biosynthesis of plasmalogens, alkyl ethers and platelet activating factor DATE: 12/15/03 Lecture 20 Regulation of phospholipid and sphingolipid catabolism Resource Material: Biochemistry 4 th Edition, by G. L. Zubay: Chapter 22 Phospholipases, sphingomyelinase and ceramidase: Enzymic mediators of cell signalling Eicosanoids: Lipidic mediators of homeostasis and pathophysiology DATE: 12/16/03 Lecture 21 Integrative regulation of metabolism Reading material will be provided Transport of body fuels through the body/liver as central storage depot for fuels (whole body regulation) Aerobic and anaerobic myocardial metabolism (regulation at organ level) Myocardial metabolism as a mechanism regulating coronary flow and alterations of myocardial metabolism as a source of pathophysiological amphiphiles. EXAM 12/17/03