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    Adriana BORRIELLO

    Insegnamento di BIOCHEMISTRY

    Corso di laurea magistrale a ciclo unico in MEDICINA E CHIRURGIA

    SSD: BIO/10

    CFU: 10,00


    Periodo di Erogazione: Annualità Singola


    Lingua di insegnamento



    Teaching language



    This course provides an overview and in-deep discussion of the main aspects of medical-oriented Biochemistry by relating molecular interactions to their effects on the organism as a whole, and on various organs and tissues, especially as related to disease mechanisms. The course also includes a discussion of the organization of macromolecules, details on their hierarchical structure and a study of their assembly into complexes responsible for specific biological processes. Topics addressing protein function is also related to enzyme function with special regard to kinetics, characterization of major metabolic pathways, and their interconnection into metabolic regulated networks.

    Textbook and course materials

    SUGGESTED REFERENCE TEXTBOOKS FOR GENERAL BIOCHEMISTRY: Thomas M. Devlin, “Textbook of Biochemistry with Clinical Correlations” Alisa Peet, Michael A. Lieberman, Allan Marks “Marks' Basic Medical Biochemistry” John W. Baynes, Marek H. Dominiczak “Medical Biochemistry” SUGGESTED TEXTBOOKS TO ADDRESS SPECIFIC TOPICS OF CLINICAL BIOCHEMISTRY: William J Marshall et Al. “Clinical Biochemistry:Metabolic and Clinical Aspects”, Churchill-Livinston (Elsevier)Nessar Ahmed (Editor): “Clinical Biochemistry”, Oxford University Press

    Course objectives

    The students will gain ability to interpret the biochemical changes occurring in the diseases and about the physiological mechanisms of the biochemical homeostasis in our cells. The main biochemical pathways regulating bio-organic molecule biosynthesis and energy production will be described and the model of pharmacological interference with biochemical pathways will be discussed. At the end of the course the students will have the bases to understand the ways to interfere with cell metabolism and the principles that drive the modern precision molecular medicine.


    The students have to be pass the examination in Chemistry and have to demonstrate the knowledge of the bases of physics and biochemical propedeutic.

    Teaching methods

    Topics 1-5 will be treated in the first semester; topics 6-10 in the second semester. Topics 11-14 will be addressed during supplemental activities dedicated to monothematic topics (ADE) and/or theoretical-practical activities (AFP). The dates of these supplemental activities will be notified in advance.

    Evaluation methods

    Exams. a mid term exams (quiz including 30 multiple choice questions) is administered at the end of the first semester. This will not sum up with the final score and it is uniquely aimed at encouraging the students to challenge with apprenticeship of the first group of topics (1 point of score will be given, to any right answer, no penalty for wrong answers). The final exam includes a written test (including 30 multiple choice questions - 1 point of score will be given, to any right answer, no penalty for wrong answers) on all topics. An oral test will follow, including specific questions on topics 2-11.

    Course Syllabus

    1 - COMPOSITION AND STRUCTURE OF THE LIVING MATTER (1 lecture) Biochemistry: definition and basic conceptsThe composition of living organismsMacromolecules: definition, composition and structures Nutritional biochemistry. Caloric content of nutrients. Micro and macronutrients 2 - PROTEIN STRUCTURE AND FUNCTIONS (6 lectures)Protein building blocks: the amino acids; structure, classification, features. Proteins: composition and structures. Protein posttranslational modifications.Structure-function relationships. Protein families. Fibrillar proteins: collagen, elastin. Biosynthesis; post-biosynthetic processing. Collagen, proteoglycans and the extracellular matrix (ECM) Globular proteins: myoglobin and hemoglobin. Muscle contractile proteins and their functions (also ref to Ca++ and Vit D metabolism). Actin ref to muscle and cytoskeleton. Hemoglobin (Hb) structure. The heme group. Hb ligands: O2, CO2, H+, 2,3-BPG, etc. Hb “T” (tense) and “R” (relaxed) states. Hb saturation (dissociation) curve. Role of 2,3-BPG in the stabilization of the “T” conformation. Bohr effect. Mechanisms for maintenance of reduced state of iron within heme: methemoglobin reductase. Transport of CO2: role of Hb, role of carbonic anhydrase, role of bicarbonates. Anemia: definition and fundamental aspects. Some examples anemias: thalassemias, sickle cell anemia, favism (see also reference to pentose phosphate pathway). 3 - THE ENZYMES (3 lectures)Classification, thermodynamics, mechanisms of enzymic catalysis.Enzyme kinetics. Michaelis-Menten equation. Km and Vmax. Kinetic control of enzyme activity. Enzyme inhibition. Enzyme inhibitors as drugs. Enzyme regulation. Allosteric regulation. Housekeeping and inducible enzymes. Compartmentalization. 4 - VITAMINS AND MINERALS: REQUIREMENTS AND FUNCTION (6 lectures)Liposoluble vitamins:A- Structure, derivatives, functions, metabolism, vit A and vision, sources, deficiency K- Structure, functions, K-dependent coagulation factors, metabolism, deficiency, clinical references to oral anticoagulantsD- Structure, functions, metabolism, biosynthesis and relationships to bone and renal disease, sources, deficiency (Rickets)E-Structure, functions, metabolism, antioxidant mechanism acitivity (ref to biochemistry of ROS), sources, Hydrosoluble vitamins:B1- Structure, functions, metabolism, coenzymes, sources, deficiency B2- Structure, function metabolism, coenzymes (FMN, FAD), sources, deficiency (Ariboflavinosis)PP- Structure, functions, coenzymes (NAD+ and NADP+), metabolism, sources, deficiency (Pellagra)B6- Structure, function metabolism, coenzyme, sources, deficiency Biotin- Structure, metabolism (role of biotinidase or holocarboxylase synthetase), functions, metabolism, sources. Pantothenate- Structure, function metabolism, sources, deficiencyFolate- Structure, biochemical processes in which folate is involved, role in C1 metabolism, folate cycle, sources, supplementation for NTD prevention, deficiency and macrocytic anemia. B12- Structure, coenzymes, absorption and role of the Intrinsic Factor, functions, metabolism, sources, deficiency (megaloblastic anemia)C- Structure, functions (ref to postbiosynthetic processing of collagen precursor), metabolism, sources, deficiency (Scurvy) Mineral and water balance:Concept of Micro and macroelementsSerum, plasma and body fluids. Control and maintenance of the intracellular volume. Role of serum proteins (eg albumin)Principles of Ca++ and bone metabolism, see also refs to Vit. D and hormones (PTH and calcitonin)Intra and extracellular ion distribution. ATP-dependent Na+/K+-pump. Ca++-pump and the function of contractile muscle proteins. The erythrocyte anion exchanger (band 3; ref to bicarbonate/CO2 transport) . 5 - METABOLIC PATHWAYS AND THEIR CONTROL (4 lectures)For all metabolic pathways, detailed under paragraphs no 4-10, the student will have to learn details of overall pathways, regulatory mechanisms, individual steps and relevant enzymes, physiological meaning, organs and tissues involved, substrates and products, energy balance, matabolic relationships with other metabolic pathways, relevance human disease mechisms and treatments whereas appropriate. Basic concepts. The regulation of metabolic pathways (see also: rate limiting enzymes, enzyme regulation under “Enzymology”). Digestion and absorption of basic nutritional constituents.Major metabolic pathways and their control: carbohydrates, lipids, amino acids (amino group and carbon skeleton). Fundamental aspects of purine and pirimidine biosynthesis (substrates, co-substrates, coenzymes, regulation, antagonists) and catabolism (uric acid formation and its inhibitors)Fundamentals of special pathways: heme catabolism and bilirubin disposal; porphyrin biosynthesis, catecholamine biosynthesis and degradation, histamine biosynthesis, tryptophan derivatives and serotonine biosynthesis. Fundamentals of glycoconjugates.6 - LIPIDS (4 lectures)Biosynthesis, storage, and utilization of fatty acids and triacylglycerols; beta-oxidation; odd carbon fatty acid degradation; carnitine shuttle system; fate of glycerol (ref. to gluconeogenesis) Fatty acid biosynthesis. Keton bodies: biosynthesis and utilization. The liver and keton bodies (also ref to ketogenic aminoacids)omega-3 and omega-6 FA. Sources and biomedical implications; arachidonic acid and eicosanoids; biosynthesis of thromboxanes and prostaglandins. Role of acetyl salicylic acid Cholesterol: structure, function and role as the steroid precursor, role in lipoprotein compositionLipoproteins: classification, biosynthesis and metabolismand their biomedical implications. The LDL receptors and scavenger receptors. Ref to type IV hypercholestrololemiaPathways of metabolism of complex lipids. Biological membranes: composition, structure, receptors (also ref to: a-signal transduction pathways; b-glycoproteins and proteoglycans) Classes membrane lipids. Glycerophospholipids and sphingolipids or glycosylceramides. Biosynthesis of membrane phospholipids7 - CARBOHYDRATES (3 lectures)Carbohydrate: structure and classification. Mono- and disaccharides. Glycosides. Polysaccharides (homo- and hetero-). Starch and Glycogen. Proteoglycans and Glycoproteins. Complex heteropolysaccharidesMajor metabolic pathways and their control; Glycolysis, Gluconeogenesis, Pentose phosphate pathway. Glycolysis: rate-limiting enzymes. Hexokinase and glucokinase. PFK1 and PFK2. Irreversible steps. Regulation mechanisms, Balance under aerobic and anaerobic conditions (see also ref to Cori cycle)Pentose phosphate pathway. Role in the production of NADPH and ribose. Role in glucose oxidation. The enzyme G6PD features and deficit (Favism, ref to the Hb paragraph)). Glycogen: structure, metabolism and regulation. Glycogen metabolism and relevant signal transduction pathways. Glycogen 6-P fate within muscle and liver tissues: differential expression of glucose 6 phosphatase. Gluconeogenesis: substrates for glucose resynthesis: pyruvate, glycerol, oxaloacetate (also ref to glucogenic amino acids). Energy requirement. Inverse regulation of pyruvate kinase and PEP-CK. Carbohydrate-related special pathways: Cori cycle and role of LDH. Glucose-Ala pathway role of GPT (ALT). Glycoconjugates. The extracellular matrix: composition and organization. 8 - INTERMEDIATE METABOLISM, BIOENERGETICS, MITOCHONDRIA, AND OXIDATIVE METABOLISM (2 lectures)Metabolic fate of pyruvate in mitochondria: the pyruvate dehydrogenase reactionKrebs tricarboxylic acid cycle (TCA). Reactions and intermediates, productsTCA anaplerotic reactionsThe relationships between TCA and urea cycle (Krebs bicycle)Shuttle systems; malate-aspartate shuttle (reversible); glycerophosphate shuttle (irreversible)Mitochondrial respiratory chain and oxidative phosphorylation. The H+ (proton) pump and the generation of the electrochemical proton gradient. Coupling of electron transport and ATP biosynthesis. The F-ATPase rotary motorsRespiratory chain inhinitors and modulators 9 - AMINO ACID METABOLISM (4 lectures)Amino groupsDisposal of amino acid nitrogen. The role of aminotransferases (ALT and AST) The glutamine synthetase/glutaminase system (organ distribution, functional meaning)Role of Glucose-Ala cycle in amino group transport in circulationUrea cycle. Carbon skeleton Ketogenic and glucogenic amino acids Correlations with gluconeogenesis. Metabolism of specific amino acidsBiogenic amines (indolamines, catecholamines, histamine) Methionine metabolism (general features; also ref to folate and B12) Amino acids as neurotransmitter or their precursors (GABA, glycine, Phe/Tyr, Trp) Nutritional features of aminoacidsEssential vs non-essential amino acids Dietary protein content and insulin release10 - OTHER PATHWAYS AND CORRELATIONS (2 lectures)Heme metabolism.Purine and pyrimidine nucleotide metabolism.Metabolic interrelationships. 11 - CELL-CELL COMMUNICATION Cytokines and hormones. Fundamentals of Signal Transduction. Fundamental notions on inflammatory cytokines. Biochemistry of hormones. Classification and mechanism of action (ref signal transduction mechanisms). Special focus on insulin: structure and biosynthesis; insulin receptor pathways; effects on carbohydrate tissue utilization; Peptide and protein hormones: classification, site of production, regulation of release and target tissues (also ref to carbohydrate metabolism and calcium metabolism) Catecholamines (also ref to amino acid metabolism)Thyroid hormones (biosynthesis, activities) Steroid hormones: classification and biosynthesis (ref to cholesterol metabolism); mechanism of action; The steroid and thyroid receptor superfamily and responsive elements12 - THE BIOCHEMICAL BASES OF OTHER PHYSIOLOGICAL PROCESSESProgrammed Cell Death and Cancer. One carbon metabolism (ref to folate biochemistry) 13 - RECOMBINANT DNA AND ADVANCED BIOTECHNOLOGIES: BASIC CONCEPTS14 - THE “OMICS” REVOLUTION

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