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Randolph Rill, Ph.D., Course Director [email protected] (850) 644-3661 Medical Biochemistry & Genetics BMS 6204 2005 – 2006 Course Schedule Date Instructor Activity Read1 Related2 Topic & Context Major Concepts LCME Step 1 Connection Week 1 BD1; MG1; 1/3 Rill Lecture 1 1/3 Rill Orientation MG2 21-2 MG2 1/4 Rill Lecture 2 6-11 ; BD29, RS3I,II 1/5 Rill Lecture 3 DNA structure & stability; Chromatin Structure; DNA Replication Genetic information flow; genome organization, genetic diseases: types & impacts; cancer Course philosophy, Present & future medicine, USMLE and NBME expectations, Studying biochemistry; categories of genetic diseases DNA structure & stability, Chromosome structure: nucleosome, centromere, telomere; replication: DNA polymerase types, replisome, 1.1.1: DNA structure, stabili proofreading 374-6 ; MG329- BD29 Medical Genetics Genetic information; Overview of Genetic Diseases; Cancer: a Disease of the Genome Course mechanics: syllabus, schedule, goals, importance; Major elements of Medical Biochem. & Genetics Cell Biochemistry> RS3IIC-F 33, MG3 36- Cell Biochemistry> Mutation types and mechanisms DNA damage: UV, chemicals, radiation, spontaneous; DNA repair: excision & SOS repair, AP nuclease; mutagens, Ames test 1.1.1: DNA damage, repair; 40 MG2 11-13; 15; 1722 1/6 Rill Lecture 4 BD30 Cell Biochemistry> ; RS3III RNA polymerase, transcription factor; RNA polyadenylation, capping, 1.1.1: Gene structure, organi Transcription: RNA Synthesis splicing; RNA stability, ribonuclease and Processing Week 2 MG2 1/9 Rill Lecture 5 16,17 ; BD31 Genetic code; mRNA translation, tRNA charging, ribosome subunits; protein processing & turnover: signal se RS3 1/9 Rill Cell Biochemistry> Translation: Protein Synthesis & Processing IV Tutorial 1 MG2 13-15 ; Cell Biochemistry> 1/10 Stefanovi c V Lecture 6 BD32 RS3 ; 8IIB; Control of Gene MG10212 Expression Bacterial operons: operators, repressors, activators; Mammalian response elements, enhancers, transcription fa -13 1/11 Clark 1/12 Clark, Team Workshop Workshop Quiz 1 SGL1 Medical Informatics Workshop (1): Health Information, Diagnosis & Treatment resources Medical Informatics Workshop (2) Practice with Health Information, Diagnosis & Treatment resources; Case 1: Failed Immunity HIV and AIDS; retrovirus: virus replication, reverse transcriptase & inhibitors, protease inhibitors; transcrip MG2 1/13 Paull Lecture 7 22-27 ; Cell Biochemistry> MG6; MG8161- Cell cycle, mitosis & meiosis; recombination: Holliday junction, transposon; cytogenetics, abnormalities of ch Chromosome Segregation and Rearrangements; Clinical Cytogenetics 3 Week 3 1/16 1/17 No Class Paull MLK Day SGL2 Cytogenetics Exercise Medical Genetics> 1/18 Rill Lecture 8 BD39 MG11 Cell cycle, transformation; oncogenes; apoptosis; multi-factorial disease; metastasis, DNA-directed th Cell Cycle Control, Cancer Progression, Oncogenes, Treatment 1/18 Rill Tutorial 2 Medical Genetics> 1/19 1/19 Rill Rill Lecture 9 MG4 Single gene disorders, autosomal dominant & recessive; population genetics (Hardy-Weinberg princi Mendelian inheritance patterns of genetic diseases Medical Informatics Workshop (3): NCBI, PubMed; MMBID; Workshop Quiz 2 SGL 3 Case 2: Predisposed to Tumors Oncogenes, p53, apoptosis, splicing, UV damage, DNA repair Medical Genetics> 1/20 Rill Date Instructor Lecture 10 MG5; MG12 Activity Non-Mendelian inheritance Sex linkage; mitochondrial inheritance; mosaic, multifactorial Inheritance Medical Biochemistry & Genetics Topic Read Major Concepts Week 4 MG3 1/23 Rill Lecture 11 1/24 Team SGL 4 42-55 ; Medical Genetics> B3.2; Detection of gene variants: MG3 299 Medical applications of biotechnology MG13 BD33 Case 3: Susceptible to Cancer; Gene libraries, gene mapping, cytogenetics, RFLP, VNTR, PCR, SNP, m Transcription factors, cAMP-mediated phosphorylation, CREB, gene regulators; Case 4: Heritable Mental Retardation Mental retardation, X-linked inheritance, restriction fragment length polymorphism (RFLP), DNA m 1/24 Rill Tutorial 3 1/25 Rill Lecture 12 1/26 Rill Review 1/27 Wrap-up & Perspectives: Molecular Genetic Approaches to Cancer & Genetic Diseases EXAM 1 Week 5 Cell Biochemistry> 1/30 Rill Lecture 13 BD2 5-15 Amino acid structure, categories; Protein structure, folding, stability, association, subunits Amino acids & proteins Blood> 1/31 Rill Lecture 14 BD2 15-20 BD3 ; Plasma> 21-5 Plasma proteins: types, separation & characterization Protein fractionation, plasma composition, electrophoresis, chromatography, serum albumin; osmoti 1/31 Team SGL 5 1/31 Rill Tutorial 5 270-1 ; Case 5: Developmental Delay & MG596-98 Mental Retardation MG12 Muscle structure, gene splicing, dystrophin, extracellular matrix, cytoskeleton Blood> BD3 2/1 Rill Lecture 15 21-5 ; 121 BD10 MG5 96-98 MG4 ; 69,71 Plasma > Transport proteins, iron transport, iron storage, copper transport, membrane transporter, Wilson and M -2 -3 Carriers, Iron & Copper Transport & Metabolism 2/2 Team SGL 6 Cases 6: A Weak Heart DNA triplet repeat expansion, glycolysis, protein structure Quiz 3 Case 7: Dementia protein aggregation, amyloid plaque, b-sheet, lipoproteins Blood> 26-30 2/3 Rill Lecture 16 BD3 ; BD11135 MG13 287 Plasma> Haptoglobulin & hemopexin, protease inhibitor, emphysema, acute-phase response, CRP, macrophag Defensive proteins, Antibodies Week 6 Blood> 2/6 Rill Lecture 17 BD4 BD2 31-9 10-13 Respiration> ; RS2IVA,B Erythrocytes> Respiration, Hemoglobin & myoglobin structure, protein secondary structure, alpha-helix, sickle cell Oxygen Transport: Myoglobin & Hemoglobin Blood> 2/7 Rill Lecture 18 BD4 35-41 ; MG333-34 Respiration> MG3 346 Allostery, effectors, altitude adaptation, methemoglobinemia, hemoglobinopathies, globin genes, thal Erythrocytes> Oxygen Transport Effectors, Anemias 2/7 Team SGL 7 2/7 Rill Tutorial 6 Case 8: Copper Transport Diseases Copper enzymes, carriers & P-ATPase transporters Blood>Respiration> 72-7 2/8 Rill Lecture 19 BD7 ; BD22283 Erythrocytes> CO2 hydration & acidity, membrane transporters, coupling of oxygen and carbon dioxide transport, B -90 Carbon Dioxide Hydration & Transport 2/9 Team SGL 8 Quiz 4 Case 9: Iron-Related Disease Redox chemistry, cytochromes, collagen crosslinking, iron transport and storage Case 10: Failed Defenders Plasma proteins, mannose-binding protein, ELISA, Western blot 28-10 BD ; Blood>Respiration> 79- 2/10 Rill Lecture 20 BD7 80 ; BD22290 RS2 II,III Instructor Acid-base chemistry, pKa, Henderson-Hasselbach equation, pH buffers, acidosis, alkalosis Acid-Base Balance -4 Date Erythrocytes> Activity Read Medical Biochemistry & Genetics Topic Major Concepts Week 7 Blood & Cell Biochemistry> 2/13 Rill Lecture 21 BD5 RS2 V Catalysis, transition state, free energy, isozymes & isoforms, Michaelis-Menten kinetics, inhibitors, Enzyme Kinetics 2/14 Rill Lecture 22 2/14 Team SGL 9 2/14 Rill Tutorial BD2 8-12 Blood & Cell Biochemistry> ; RS2 BD552-3 I, III Case 11: Oxygen Deficiency RS8 2/15 Rill Lecture 23 II Team BD6 Rill Blood> Plasma> Platelets, coagulation pathways, proenzyme, cascade, fibrin, fibrinolysis, plamin, plasminogen activa 91-3 Platelet Aggregation & Coagulation SGL 10 Case 12: Chest Pains isozymes, creatine kinase, lactate dehydrogenase, troponin Quiz 5 Case 13: Inappropriate Clotting coagulation cascade, thrombin regulation, fibrinolysis RS8 2/17 Hemoglobin oxygen binding, cooperativity, hematocrit, globin genes; Redox reactions, cytochrome b ; MG5 2/16 Enzyme specificity, hydrolyase & other enzyme classes, acid-base catalysis, serine protease, protein Enzyme Mechanisms Lecture 24 II Blood> ; BD6 Plasma> MG5 Fibrinolysis, hemophilia, membrane signaling, second messenger, embolism, anti-thrombolytic & 'clo 91-3 Homeostasis & Thrombosis Week 8 2/20 Rill Lecture 25 2/21 Team SGL 11 2/21 Rill Blood>Erythrocytes>Cell Membranes Membrane bilayer, glycolipids, membrane transporters & other proteins, glycoproteins, Fluid Mosaic & Cytoskeleton BD7 Rill Lecture 26 BD8 83-92 Rill Case 15: Lung Disease ion transporters, immunofluorescence, glycosylation, gene therapy, chaperone Review I ; Cell Biochemistry> I,IIIB;VA,B Bioenergetics, 4 2/23 Skin proteins, transsglutaminase, keratin, crosslinking, Schiff's base; Collagen classes, collagen ass Tutorial 8 RS1 2/22 Case 14: Bad Skin High Energy Compounds ATP, high energy phosphates,, free energy from oxidation, redox reactions, mitochondria, electron tr 2/24 EXAM 2 Week 9 Cell Biochemistry> 2/27 Rill Lecture 27 BD8 92-6 RS4 VC-E Chemiosmotic hypothesis, proton gradient, ATP-synthase, P:O ratio, respiration poisons Oxidative Phosphorylation RS5 I,III ; 6IIIA; 2/28 Rill Lecture 28 GI Tract> + BD9 Digestive enzymes; dietary carbohydrates; bile salts, emulsions & micelles; H 7I; /K+ pump; pa Digestion and Transport 9IIA-E 2/28 Team SGL 12 2/28 Rill Tutorial 8 3/1 Rill Lecture 29 Case 16: Yellowed Skin BD10 115- RS4 III ; Team VI SGL 13 Quiz 6 3/3 Rill Lecture 30 BD10 GI Tract> RDAs; enzyme cofactors, oxidoreductase, transferase; trace minerals in enzymes 23 7 3/2 Erythrocytes, reticulocytes, bilirubin, SDS-PAGE, cytoskeleton, mRNA, Northern blot Water Soluble Vitamins & Minerals Case 17: Early Mental Decline Protein processing, aggregation, Golgi, protein secondary structure Case 18: Night Blindness Vitamin A, visual pigments, rhodopsin, signaling, sodium channel, protein structure GI Tract> 109-15 Vitamin A & vision, Vitamin D & bone, Vitamin E & antioxidants Fat-Soluble Vitamins, Nutrition NO CLASS 3/6 Date Instructor SPRING BREAK: MARCH 6-10 Activity Read Medical Biochemistry & Genetics Topic Major Concepts Week 10 Blood> Respiration> 3/13 Rill Lecture 31 BD11 125- 33, 137 RS5 VA-F2; VIII Erythrocytes> Glycolysis, pentose phosphate pathway, ATP , anaerobic metabolism, lactic acidosis, NADH, NADP Anaerobic Glucose Utilization Blood> Respiration> 3/14 Rill Lecture 32 BD11 133-6 BD10 114-21 Oxidation, superoxide dismutase, catalase, glutathione metabolism, reductases, hemolytic anemia, an Erythrocytes> Reactive Oxygen Species (ROS) 3/14 Team SGL 14 3/14 Rill Tutorial 9 Case 19: Vitamin Deficiency Disease B-vitamins, thiamin, decarboxylase, transketolase Liver and Muscle> 3/15 Rill Lecture 33 BD12 RS5 IV; VI Glycogen synthesis, glycogenolysis; glucagon, cAMP-dependent signaling, protein kinase A (PKA), Glycogen metabolism 3/16 Team SGL15 Case 20: Cyanosis Redox reactions, cytochrome b5 reductase, microcephaly Quiz 7 Case 21: Malaria Resistance Protozoa, RBC metabolism, glutathione reductase, flavokinase, B vitamins Liver and Muscle> 3/17 Rill Lecture 34 BD20 243-52 Glucose Homeostasis via Hormones Gluconeogenesis, glycolysis; hormone control of blood glucose via glucagon & insulin Week 11 Liver and Muscle> 3/20 3/21 Rill Rill Lecture 35 Lecture 36 3/21 Team SGL 16 3/21 Rill Tutorial 10 BD13 BD14 RS4 RS6 Rill Lecture 37 3/23 Team SGL 17 BD15 Pyruvate Dehydrogenase & Tricarboxylic Acid Cycle Regulation Oxidative Metabolism of Fatty Acids Case 22: Hemolytic Anemia RBC metabolism and redox state, pentose phosphate pathway X IV,V ; Pyruvate dehydrogenase (PDH), acetylCoA oxidation, dehydrogenases, reducing equivalents (NADH −Οξιδατιον, οδδ−χηαιν & υνσατυρατεδ φαττψ αχιδσ, ενε σ III.B; IX; Liver and Muscle> RS6 3/22 IV β Liver and Adipose> Biosynthesis of Fatty MG7138 Acids Fatty acid (FA)-CoA synthase, acetylCoA carboxylase,malate shuttle, FA elongation, desaturation, tr Case 23: Vitamin Deficiency Anemia RBC metabolism and redox state, pentose phosphate pathway; Vitamin B12 transport, folate metabol Quiz 8 MG7 Fig7.3 Case 24: Insufficient Energy, Easy Exhaustion Glycolysis, glycogen metabolism, phosphofructokinase Liver> II, IV 3/24 Rill Lecture 38 BD18 RS7 ; MG13280 Amino Acid Metabolism Amino acid synthesis; degradation: transaminases, oxidative deamination, dehydratases; carbon skele Week 12 Liver & Muscle> 3/27 Rill Lecture 39 3/28 Team SGL 18 3/28 Rill Tutorial 11 BD20 Glucose: Insulin Action & Diabetes; Alcoholism Cori cycle; glucose from amino acids, lipids; insulin dependent & independent diabetes, Hb1C, metab Case 25: Aciduria Lipid oxidation, ketone bodies, methylmalonyl-CoA mutase Case 26: Alcoholism Hypoglycemia, hyperuricemia, alcohol dehydrogenase, ketoacidosis 3/29 Rill 3/30 Rill 3/31 Date Lecture 40 BD20 Energy Metabolism Wrap-up Eenrgy metabolism in Fed, Fasting and stressed states; comparison of adipose, brain, liver, & muscle Review EXAM 3 Instructor Activity Medical Biochemistry & Genetics Topic Read Major Concepts Week 13 4/3 Rill Lecture 41 BD19 RS9 II.J Muscle: Structure & Energy Metabolism Muscle protein functions, sarcomeres, contraction stages; ATP and creatine phosphate usage Liver> 4/4 Rill 4/4 Team 4/4 Rill Lecture 42 BD16 RS6 VI SGL 19 Biosynthesis of Cholesterol HMG CoA reductase regulation & inhibitors, statin, mevalonate, squalene synthase, bile salts, steroid Case 27: Diabetes Symptoms Insulin receptors, hyperinsulinemia, hyperglycemia, insulin processing, Western blot Tutorial 13 Liver and Vascular> 4/5 Rill 4/6 Team 4/6 Lecture 43 BD17 RS6 III.B, VII SGL 20 Quiz 9 Lipoproteins & Lipid Transport Apolipoproteins A, B, C, E; chylomicrons; lipoprotein types (VLDL, LDL, HDL); Lipases Case 28: Ambiguous Gender steroid hormones, sex determination Case 29: Mistaken Gender Reproductive organ development, androgen receptors, polymerase chain reaction, Western blot Liver and Vascular> 4/7 Rill Lecture 44 BD17 RS9 II.K Cholesterol Transport, Atherogenesis Lipoprotein receptors, synthesis, recycling; exogenous & endogenous lipids plaque & atherogenesis Week 14 RS6 4/10 Rill Lecture 45 BD25 321-6 X ; Cell Biochemistry> Complex Lipids: MG7149 Glycerol-Conjugated (Table7.5) Lipids Fatty acid & lipid nomenclature; phospholipid types, glycoproteins and GP anchors; phospholipase sp Cell Biochemistry> 4/11 Rill Lecture 46 BD25 327-31 Complex Lipids: Sphingolipids, cerebrosides, gangliosides & other glycolipids; lipid storage diseases SphingosineConjugated Lipids 4/11 Team SGL 21 4/11 Rill Tutorial 14 Case 30: Arteries at Risk Cholesterol metabolism, statin, HMG-CoA reductase, lipoproteins, reporter gene Connective Tissues> 4/12 Rill 4/13 Rill Lecture 47 BD26 333-7 IVC Collagen & Elastin; Proteoglycans Collagen classes, synthesis & assembly; elastin; crosslinking reactions; SGL 22 Case 31: Defective Lipid Transport apolipoproteins, chylomicrons, VLDL, LDL, HDL, Apo B-48, 100, glycosylation Quiz 10 Case 32: Insulin Deficiency Ion and pH balance, hypertension, bone demineralization RS2 Liver & Kidney> 4/14 Rill Lecture 48 BD27 249-50 RS7 III, V ; IIL 9 Nitrogen Metabolism & Excretion Urea cycle, glutamine, glutamate dehydrogenase, argininosuccinate synthase, arginase; NO productio Week 15 ; 7VIIF; RS6 4/17 Rill Lecture 49 BD27 VIB 9IIF 4/18 Team SGL 23 Liver> Heme & Bile Metabolism Heme synthesis, bilirubin metabolism, jaundice; bile metabolism, cholesterol elimination Case 33: Starvation Serum albumin, protein & carbohydrate metabolism, carcinogenesis, aflatoxins, DNA damage, P450 Case 34: Lysosomal Storage Disease Case 35: Cartilage Defects 4/18 Rill Tutorial 15 RS7 4/19 Rill Collagen classes, synthesis & assembly; elastin; crosslinking reactions; exon skipping Lecture 50 BD28 VIIE Cell Biochemistry> MG12251 Nucleotide Metabolism IMP, PRPP synthetase, aminotransferase; UMP; ribonucleotide reductase, thymidylate synthase, DHF -3 4/20 Rill Review 4/21 EXAM 4 4/24 FINAL Week 16 1 NBME Subject Exam in Biochemistry Reading assignment before lecture; 2Related material in other course texts. BD = Baynes & Dominiczak, Medical Biochemistry; MG = Jorde et al., Medical Genetics; RS = Review Series in Biochemistry 333-7 Chapters and pages or sections are indicated; for example, BD26 chapter 26, pages 333-337. refers to Baynes and Dominiczak,