Medical Biochemistry & Genetics BMS Course Schedule

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1 Medical Biochemistry & Genetics BMS Course Schedule Randolph Rill, Ph.D., Course Director (850) Date Instructor Activity Read 1 Related 2 Topic & Context 1/3 Rill Lecture 1 1/3 Rill Orientation BD1; MG1; MG /4 Rill Lecture 2 BD29, 1/5 Rill Lecture 3 BD ; MG , MG /6 Rill Lecture 4 BD30 MG ; RS3 I,II RS3 IIC-F 11-13; 15; 17- MG2 22 ; RS3 III Week 1 Medical Genetics Genetic information; Overview Genetic information flow; genome organization, genetic diseases: of Genetic Diseases; Cancer: a types & impacts; cancer Disease of the Genome Course mechanics: syllabus, schedule, goals, importance; Major elements of Medical Biochem. & Genetic s DNA structure & stability; Chromatin Structure; DNA Replication Mutation types and mechanisms Transcription: RNA Synthesis and Processing 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, proofreading DNA damage: UV, chemicals, radiation, spontaneous; DNA repair: excision & SOS repair, AP nuclease; mutagens, Ames test RNA polymerase, transcription factor; RNA polyadenylation, capping, splicing; RNA stability, ribonuclease LCME Step 1 Connection 1.1.1: DNA structure, stabili 1.1.1: DNA damage, repair; 1.1.1: Gene structure, organi Week 2 1/9 Rill Lecture 5 BD31 1/9 Rill Tutorial 1 1/10 Stefanovi c Lecture 6 BD32 1/11 Clark Workshop 1/12 Clark, Team Workshop Quiz 1 SGL1 MG2 16,17 ; RS3 IV MG ; Translation: Protein Synthesis & Processing RS3 V ; 8 IIB ; Control of Gene MG Expression -13 Medical Informatics Workshop (1): Health Information, Diagnosis & Treatment resources Medical Informatics Workshop (2) Practice with Health Information, Diagnosis & Treatment resources; Case 1: Failed Immunity Genetic code; mrna translation, trna charging, ribosome subunits; protein processing & turnover: signal se Bacterial operons: operators, repressors, activators; Mammalian response elements, enhancers, transcription fa HIV and AIDS; retrovirus: virus replication, reverse transcriptase & inhibitors, protease inhibitors; transcrip

2 1/13 Paull Lecture 7 MG ; MG6; MG /16 No Class MLK Day 1/17 Paull SGL2 Cytogenetics Exercise Chromosome Segregation Cell cycle, mitosis & meiosis; recombination: Holliday junction, transposon; cytogenetics, abnormalities of ch and Rearrangements; Clinical Cytogenetics Medical Genetics> Week 3 1/18 Rill Lecture 8 BD39 MG11 1/18 Rill Tutorial 2 1/19 Rill Lecture 9 MG4 1/19 Rill Workshop Quiz 2 Cell Cycle Control, Cancer Progression, Oncogenes, Treatment Medical Genetics> Mendelian inheritance patterns of genetic diseases Medical Informatics Workshop (3): NCBI, PubMed; MMBID; Cell cycle, transformation; oncogenes; apoptosis; multi-factorial disease; metastasis, DNA-directed th Single gene disorders, autosomal dominant & recessive; population genetics (Hardy-Weinberg princi SGL 3 Case 2: Predisposed to Tumors Oncogenes, p53, apoptosis, splicing, UV damage, DNA repair 1/20 Rill Lecture 10 MG5; MG12 Medical Genetics> Non-Mendelian inheritance Date Instructor Activity Read Medical Biochemistry & Genetics Topic 1/23 Rill Lecture 11 BD33 Sex linkage; mitochondrial inheritance; mosaic, multifactorial Inheritance Week 4 MG ; MG3 B3.2; Medical Genetics> Detection of gene variants: Gene libraries, gene mapping, cytogenetics, RFLP, VNTR, PCR, SNP, m MG Medical applications of biotechnology 1/24 Team SGL 4 Case 3: Susceptible to Cancer; 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 Wrap-up & Perspectives: Molecular Genetic Approaches to Cancer & Genetic Diseases 1/27 EXAM 1 1/30 Rill Lecture 13 BD /31 Rill Lecture 14 BD ; BD Amino acids & proteins Plasma> Plasma proteins: types, separation & characterization Week 5 Amino acid structure, categories; Protein structure, folding, stability, association, subunits Protein fractionation, plasma composition, electrophoresis, chromatography, serum albumin; osmoti

3 1/31 Team SGL 5 MG ; Case 5: Developmental Delay & Mental Retardation MG5 Muscle structure, gene splicing, dystrophin, extracellular matrix, cytoskeleton 1/31 Rill Tutorial 5 2/1 Rill Lecture 15 BD ; MG ; BD MG4 69,71 Plasma > -3-2 Carriers, Iron & Copper Transport & Metabolism Transport proteins, iron transport, iron storage, copper transport, membrane transporter, Wilson and M 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 2/3 Rill Lecture 16 BD ; BD MG Plasma> Defensive proteins, Antibodies Haptoglobulin & hemopexin, protease inhibitor, emphysema, acute-phase response, CRP, macrophag Week 6 2/6 Rill Lecture 17 BD BD ; RS2 IVA,B Respiration> Respiration, Hemoglobin & myoglobin structure, protein secondary structure, alpha-helix, sickle cell Oxygen Transport: Myoglobin & Hemoglobin 2/7 Rill Lecture 18 BD ; MG MG3 346 Respiration> Allostery, effectors, altitude adaptation, methemoglobinemia, hemoglobinopathies, globin genes, thal Oxygen Transport Effectors, Anemias 2/7 Team SGL 7 Case 8: Copper Transport Diseases Copper enzymes, carriers & P-ATPase transporters 2/7 Rill Tutorial 6 2/8 Rill Lecture 19 BD ; BD Respiration> Carbon Dioxide Hydration & Transport CO 2 hydration & acidity, membrane transporters, coupling of oxygen and carbon dioxide transport, B 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

4 2/10 Rill Lecture 20 BD ; BD ; BD RS2 II,III Respiration> Acid-Base Balance Acid-base chemistry, pk a, Henderson-Hasselbach equation, ph buffers, acidosis, alkalosis Date Instructor Activity Read Medical Biochemistry & Genetics Topic 2/13 Rill Lecture 21 BD5 RS2 V Blood & Enzyme Kinetics Week 7 Catalysis, transition state, free energy, isozymes & isoforms, Michaelis-Menten kinetics, inhibitors, 2/14 Rill Lecture 22 BD28-12 ; BD I, III RS2 Blood & Enzyme Mechanisms Enzyme specificity, hydrolyase & other enzyme classes, acid-base catalysis, serine protease, protein 2/14 Team SGL 9 Case 11: Oxygen Deficiency Hemoglobin oxygen binding, cooperativity, hematocrit, globin genes; Redox reactions, cytochrome b 2/14 Rill Tutorial 2/15 Rill Lecture 23 BD6 RS8 II ; MG Plasma> Platelet Aggregation & Coagulation Platelets, coagulation pathways, proenzyme, cascade, fibrin, fibrinolysis, plamin, plasminogen activa 2/16 Team SGL 10 Case 12: Chest Pains isozymes, creatine kinase, lactate dehydrogenase, troponin Quiz 5 Case 13: Inappropriate Clotting coagulation cascade, thrombin regulation, fibrinolysis 2/17 Rill Lecture 24 BD6 RS8 II ; MG Plasma> Homeostasis & Thrombosis Fibrinolysis, hemophilia, membrane signaling, second messenger, embolism, anti-thrombolytic & 'clo Week 8 2/20 Rill Lecture 25 BD7 Cell Membranes & Cytoskeleton Membrane bilayer, glycolipids, membrane transporters & other proteins, glycoproteins, Fluid Mosaic 2/21 Team SGL 11 Case 14: Bad Skin Skin proteins, transsglutaminase, keratin, crosslinking, Schiff's base; Collagen classes, collagen ass Case 15: Lung Disease ion transporters, immunofluorescence, glycosylation, gene therapy, chaperone 2/21 Rill Tutorial 8 2/22 Rill Lecture 26 BD /23 Rill Review RS1 I ; 4 I,IIIB;VA,B Bioenergetics, High Energy Compounds ATP, high energy phosphates,, free energy from oxidation, redox reactions, mitochondria, electron tr

5 2/24 EXAM 2 2/27 Rill Lecture 27 BD VC-E RS4 Oxidative Phosphorylation RS5 I,III ; Week 9 Chemiosmotic hypothesis, proton gradient, ATP-synthase, P:O ratio, respiration poisons 2/28 Rill Lecture 28 BD9 6 IIIA ; 7 I ; GI Tract> Digestion and Transport Digestive enzymes; dietary carbohydrates; bile salts, emulsions & micelles; H + /K + pump; pa 9 IIA-E 2/28 Team SGL 12 Case 16: Yellowed Skin Erythrocytes, reticulocytes, bilirubin, SDS-PAGE, cytoskeleton, mrna, Northern blot 2/28 Rill Tutorial 8 3/1 Rill Lecture 29 BD RS4 III ; 7 VI GI Tract> Water Soluble Vitamins & Minerals RDAs; enzyme cofactors, oxidoreductase, transferase; trace minerals in enzymes 3/2 Team SGL 13 Case 17: Early Mental Decline Protein processing, aggregation, Golgi, protein secondary structure Quiz 6 Case 18: Night Blindness Vitamin A, visual pigments, rhodopsin, signaling, sodium channel, protein structure 3/3 Rill Lecture 30 3/6 NO CLASS BD GI Tract> Fat-Soluble Vitamins, Nutrition SPRING BREAK: MARCH 6-10 Date Instructor Activity Read Medical Biochemistry & Genetics Topic Vitamin A & vision, Vitamin D & bone, Vitamin E & antioxidants Week 10 Respiration> 3/13 Rill Lecture 31 BD , 137 RS5 VA-F2; VIII Glycolysis, pentose phosphate pathway, ATP, anaerobic metabolism, lactic acidosis, NADH, NADP Anaerobic Glucose Utilization Respiration> /14 Rill Lecture 32 BD11 BD10 Oxidation, superoxide dismutase, catalase, glutathione metabolism, reductases, hemolytic anemia, an Reactive Oxygen Species (ROS) 3/14 Team SGL 14 Case 19: Vitamin Deficiency Disease B-vitamins, thiamin, decarboxylase, transketolase 3/14 Rill Tutorial 9

6 3/15 Rill Lecture 33 BD12 RS5 IV; VI Liver and Muscle> Glycogen metabolism Glycogen synthesis, glycogenolysis; glucagon, camp-dependent signaling, protein kinase A (PKA), 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 3/17 Rill Lecture 34 BD Liver and Muscle> Glucose Homeostasis via Hormones 3/20 Rill Lecture 35 BD13 RS4 IV Liver and Muscle> 3/21 Rill Lecture 36 BD14 Pyruvate Dehydrogenase & Tricarboxylic Acid Cycle Regulation III.B; IX; Liver and Muscle> RS6 X Oxidative Metabolism of Fatty Acids Gluconeogenesis, glycolysis; hormone control of blood glucose via glucagon & insulin Week 11 Pyruvate dehydrogenase (PDH), acetylcoa oxidation, dehydrogenases, reducing equivalents (NADH β Οξιδατιον, οδδ χηαιν & υνσατυρατεδ φαττψ αχιδσ, ενε σ 3/21 Team SGL 16 Case 22: Hemolytic Anemia RBC metabolism and redox state, pentose phosphate pathway 3/21 Rill Tutorial 10 3/22 Rill Lecture 37 BD15 RS6 IV,V ; MG7 138 Liver and Adipose> Biosynthesis of Fatty Acids Fatty acid (FA)-CoA synthase, acetylcoa carboxylase,malate shuttle, FA elongation, desaturation, tr 3/23 Team SGL 17 Case 23: Vitamin Deficiency Anemia RBC metabolism and redox state, pentose phosphate pathway; Vitamin B12 transport, folate metabol Fig7.3 Case 24: Insufficient Energy, Easy Quiz 8 MG7 Exhaustion Glycolysis, glycogen metabolism, phosphofructokinase 3/24 Rill Lecture 38 BD18 Liver> RS7 II, IV ; MG Amino Acid Metabolism Liver & Muscle> Amino acid synthesis; degradation: transaminases, oxidative deamination, dehydratases; carbon skele Week 12 3/27 Rill Lecture 39 BD20 Glucose: Insulin Action & Diabetes; Alcoholism Cori cycle; glucose from amino acids, lipids; insulin dependent & independent diabetes, Hb1C, metab 3/28 Team SGL 18 Case 25: Aciduria Lipid oxidation, ketone bodies, methylmalonyl-coa mutase Case 26: Alcoholism Hypoglycemia, hyperuricemia, alcohol dehydrogenase, ketoacidosis 3/28 Rill Tutorial 11

7 3/29 Rill Lecture 40 BD20 Energy Metabolism Wrap-up Eenrgy metabolism in Fed, Fasting and stressed states; comparison of adipose, brain, liver, & muscle 3/30 Rill Review 3/31 EXAM 3 Date Instructor Activity Read Medical Biochemistry & Genetics Topic Week 13 II.J Muscle: Structure & Energy 4/3 Rill Lecture 41 BD19 RS9 Metabolism Muscle protein functions, sarcomeres, contraction stages; ATP and creatine phosphate usage 4/4 Rill Lecture 42 BD16 RS6 VI Liver> Biosynthesis of Cholesterol HMG CoA reductase regulation & inhibitors, statin, mevalonate, squalene synthase, bile salts, steroid 4/4 Team SGL 19 Case 27: Diabetes Symptoms Insulin receptors, hyperinsulinemia, hyperglycemia, insulin processing, Western blot 4/4 Rill Tutorial 13 Liver and Vascular> III.B, VII 4/5 Rill Lecture 43 BD17 RS6 Lipoproteins & Lipid Transport Apolipoproteins A, B, C, E; chylomicrons; lipoprotein types (VLDL, LDL, HDL); Lipases 4/6 Team SGL 20 Case 28: Ambiguous Gender steroid hormones, sex determination 4/6 Quiz 9 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 4/10 Rill Lecture 45 BD RS6 X ; MG7 149 (Table7.5) Cholesterol Transport, Atherogenesis Complex Lipids: Glycerol-Conjugated Lipids Lipoprotein receptors, synthesis, recycling; exogenous & endogenous lipids plaque & atherogenesis Week 14 Fatty acid & lipid nomenclature; phospholipid types, glycoproteins and GP anchors; phospholipase sp 4/11 Rill Lecture 46 BD Complex Lipids: Sphingosine- Conjugated Lipids Sphingolipids, cerebrosides, gangliosides & other glycolipids; lipid storage diseases 4/11 Team SGL 21 Case 30: Arteries at Risk Cholesterol metabolism, statin, HMG-CoA reductase, lipoproteins, reporter gene 4/11 Rill Tutorial 14

8 Connective Tissues> 4/12 Rill Lecture 47 BD RS2 IVC Collagen & Elastin; Proteoglycans Collagen classes, synthesis & assembly; elastin; crosslinking reactions; 4/13 Rill 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 4/14 Rill Lecture 48 BD RS7 III, V ; 9 IIL 4/17 Rill Lecture 49 BD27 RS6 VIB ; 7 VIIF ; 9 IIF Liver & Kidney> Nitrogen Metabolism & Excretion Liver> Heme & Bile Metabolism Urea cycle, glutamine, glutamate dehydrogenase, argininosuccinate synthase, arginase; NO productio Week 15 Heme synthesis, bilirubin metabolism, jaundice; bile metabolism, cholesterol elimination 4/18 Team SGL 23 Case 33: Starvation Serum albumin, protein & carbohydrate metabolism, carcinogenesis, aflatoxins, DNA damage, P450 Case 34: Lysosomal Storage Disease 4/18 Rill Tutorial 15 4/19 Rill Lecture 50 BD28 RS7 VIIE MG Case 35: Cartilage Defects Nucleotide Metabolism Collagen classes, synthesis & assembly; elastin; crosslinking reactions; exon skipping IMP, PRPP synthetase, aminotransferase; UMP; ribonucleotide reductase, thymidylate synthase, DHF 4/20 Rill Review 4/21 EXAM 4 4/24 FINAL NBME Subject Exam in Biochemistry Week 16 1 Reading assignment before lecture; 2 Related material in other course texts. BD = Baynes & Dominiczak, Medical Biochemistry; MG = Jorde et al., Medical Genetics; RS = Review Series in Biochemistry Chapters and pages or sections are indicated; for example, BD refers to Baynes and Dominiczak, chapter 26, pages