Biochemistry Mathews Van Holde Ahern Pdf Download
Floriana Monterroza
Lo studente sar in grado di interpretare in chiave biochimica i processi biologici normali e patologici, fornendogli le conoscenze necessarie per la comprensione delle caratteristiche chimiche dei composti che costituiscono gli organismi viventi e delle correlazioni struttura-funzione degli stessi composti;delle vie metaboliche, delle loro interrelazioni, della loro regolazione e della loro distribuzione nei compartimenti cellulari;della specializzazione a livello molecolare, sovramolecolare e metabolico di cellule, tessuti ed organi. Lo studente acquisir inoltre conoscenze sulle principali tecniche di biologia molecolare, sulle modalit di analisi del genoma e del trascrittoma, sulla variabilit del genoma tra individui e le applicazioni in medicina legale, sulla produzione di proteine ricombinanti ad uso terapeutico, sulla terapia genica e la terapia sostitutiva, sulla tecnologia di produzione di OGM. Infine, lo studente apprender anche le principali metodologie per lo studio delle proteine.
The student who completes the course successfully will be able to demonstrate a solid knowledge of the biochemical basis of cellular function and tissue physiology, as well as the organization of the human genoma and the regulation of gene expression. He or she will acquire the ability to understand the biochemical basis of human disease and to understand the application of biochemical and molecular biology techniques to biological and medical issues.
The student will be assessed on his/her demonstrated ability to discuss the main course contents using the appropriate terminology. He or she must be able to demonstrate adequate knowledge of the basic issues of biochemistry and molecular biology and to apply them to biological and/or medical problems.
Lo studente al termine del corso sar capace di capire e possibilmente analizzare criticamente argomenti che coinvolgono i processi biochimici cellulari, le tecnologie di biologia molecolare e nuove frontiere teraputiche.
Lo studente potr acquisire sensibilit e spirito analitico riguardo ai processi biochimici e alla loro correlazione, alle tecnologie di studio, analisi e manipolazione degli acidi nucleici e delle proteine.
Vari tipi di lipidi. Acidi grassi saturi, insaturi e ramificati. Acidi grassi essenziali. Eicosanoidi. Stereoisomeria dei gliceridi. Triacilgliceroli. Fosfogliceridi e acido fosfatidico. Sfingolipidi. Gli steroli e gli steroidi: colesterolo, acidi biliari e derivati.
Utilizzazione e ruolo del glucosio nel metabolismo. Reazioni della glicolisi. I destini metabolici del piruvato. Reazione generale della glicolisi. Regolazione della glicolisi. Gluconeogenesi e sua regolazione. Substrati della gluconeogenesi. Ruolo del glicogeno. Glicogenolisi e glicogenosintesi. Glicogeno fosforilasi e glicogeno sintasi come modelli di enzimi interconvertibili. Regolazione del metabolismo del glicogeno. Utilizzazione e sintesi di zuccheri diversi dal glucosio (galattosio, fruttosio, pentosi).
Decarbossilazione ossidativa del piruvato. Struttura, meccanismo di azione e regolazione della piruvato deidrogenasi. I coenzimi coinvolti nell'ossidazione del piruvato e nel ciclo di Krebs. Reazioni ed enzimi del ciclo di Krebs. Reazione globale, resa energetica e regolazione. Ruolo biosintetico del ciclo di Krebs. Ruolo della via dei pentosi nella genesi di NADPH e di zuccheri a 4, 5, 7 atomi di carbonio. Reazioni e loro regolazione. Ruolo del NADPH nel metabolismo.
Ossidazione degli acidi grassi: funzione, attivazione, trasporto mitocondriale e beta-ossidazione. La carnitina. Resa energetica. Beta-ossidazione perossisomiale; catabolismo degli acidi grassi insaturi, a numero dispari di atomi di carbonio e ramificati. Formazione e destino del propionil-CoA. Formazione dei corpi chetonici e loro utilizzazione. Sintesi del palmitato: reazioni, enzimi e regolazione. Allungamento ed insaturazione degli acili. Sintesi e degradazione dei trigliceridi, fosfogliceridi e sfingolipidi. Metabolismo degli eicosanoidi. Sintesi del colesterolo e sua regolazione. Esteri del colesterolo. Metabolismo e ruolo degli acidi biliari. Trasporto dei lipidi nel sangue. Classificazione, struttura, funzione delle lipoproteine plasmatiche. Aspetti biochimici del trasporto di membrana.
Enzimologia e regolazione della sintesi proteica. RNA transfer e loro aminoacilazione. Interazioni fra ribosomi, mRNA, tRNA e fattori solubili della sintesi proteica. Velocit e richiesta energetica per la sintesi. Acquisizione della struttura tridimensionale. Modificazioni della catena polipeptidica dopo la sintesi. Esportazione delle proteine.
Recettori di membrana: classificazione. Recettori a 7 segmenti transmembrana, recettori catalitici, recettori ionotropici. Le proteine G e vie di trasduzione del segnale da essi attivate. Proteine chinasi e proteine fostafasi. Meccanismi di amplificazione e di modulazione del segnale. Recettori intracellulari: struttura e funzione. Concetto di ormone e neurotrasmettitore. Analisi delle caratteristiche biochimiche (struttura, metabolismo e vie di trasduzione del segnale attivate) delle seguenti sostanze: insulina, glucagone, catecolamine, ormoni tiroidei, ormoni steroidei (glucocorticoidi, mineralcorticoidi, androgeni, estrogeni, progestinici), acido retinoico, fattori di crescita, NO e vitamina D.
Genoma Umano: Organizzazione ed obiettivi del Progetto Genoma Umano. Il mappaggio del genoma: mappe genetiche e fisiche. Sequenziamento e annotazione del genoma: approccio gerarchico (top down) e approccio shotgun. Identificazione dei geni: il sequenziamento delle EST (Expressed Sequence Tags), la ricerca delle ORF (Open Reading Frames). Identificazione degli elementi funzionali presenti nella sequenza del Genoma Umano: progetto ENCODE.
Terapia genetica. Farmaci, proteine e vaccini ricombinanti. Cellule staminali e loro impieghi terapeutici. Principi di terapia genica: vettori virali, RNA e oligonucleotidi terapeutici. Successi e insuccessi della terapia genica.
Protein structure. Enzyme function and oxygen trasnporting molecules. Structure and function of lipids and carbohydrates. Structure and function of nucleic acids. General principles of metabolism. Detailed analysis of the metabolic pathways in glucose, lipid, nucleotide and amino acid metabolism. DNA replication and reparation, gene structure, and genome organization. Translation, post-translational modifications, and regulation of gene expression. Protein synthesis and its regulation. Molecular mechanism of signal trasnduction. Basic techniques in biochemistry and molecular biology.
Proteins Protein classification and function. Primary structure of proteins. Properties of the peptide bond. Secondary structure of proteins (alpha-helix, beta-structure): properties and bonds that stabilize it. Examples of fibrous proteins. Tertiary structure of proteins and bonds that stabilize it. Supersecondary structures and domains. Quaternary structure of proteins. Examples of monomeric and polymeric proteins. Denaturation and renaturation of proteins. Proteins as electrolytes. Oxygen carrying proteins: myoglobin and hemoglobin. Structure of heme and heme-globin ratio. The bond of oxygen to heme. Variations in the tertiary and quaternary structure induced by the bond with oxygen. Oxygenation curves of myoglobin and hemoglobin. Bohr effect. Molecular basis of CO toxicity. Fetal hemoglobins. Methemoglobin. Enzymes and coenzymes Enzymes: definition, nature, nomenclature and classification. Mechanisms of enzymatic catalysis. Enzyme kinetics: theory of Michaelis and Menten. The equation of Michaelis and Menten: Km and Vmax. Determination of enzymatic activity, definition of enzymatic unit. Factors that influence enzymatic activity. Enzyme inhibition. Regulation of enzymatic activity. Multienzymatic systems. Isoenzymes. Concept of coenzyme and the relationship between coenzymes and water-soluble vitamins. Carbohydrates Monosaccharides, disaccharides and polysaccharides. Aldonic, saccharic and uronic acids. Glycoproteins and proteoglycans. Lipids Various types of lipids. Saturated, unsaturated and branched fatty acids. Essential fatty acids. Eicosanoids. Stereoisomerism of glycerides. Triacylglycerols. Phosphoglycerides and phosphatidic acid. Sphingolipids. Sterols and steroids: cholesterol, bile acids and derivatives. Nucleotides and introduction to metabolism Meaning and structure of ribonucleotides and deoxyribonucleotides. Nucleosides di- and triphosphates. ATP and other high energy hydrolysis compounds. Concept of metabolism: catabolism and anabolism. Exergonic and endoergonic reactions. Coupled reactions. Central role of ATP in energy metabolism. The hydrolytic and oxidative stages of catabolism. Structure and function of pyridine and flavin coenzymes. Synthesis of monomers and polymers. Relationships between anabolism and catabolism. Carbohydrate metabolism Utilization and role of glucose in metabolism. Reactions of glycolysis. The metabolic fates of pyruvate. General reaction of glycolysis. Regulation of glycolysis. Gluconeogenesis and its regulation. Substrates of gluconeogenesis. Role of glycogen. Glycogenolysis and glycogenosynthesis. Glycogen phosphorylase and glycogen synthase as models of interconvertible enzymes. Regulation of glycogen metabolism. Utilization and synthesis of sugars other than glucose (galactose, fructose, pentosis). Oxidative processes: Krebs cycle and pentose phosphate pathway Oxidative decarboxylation of pyruvate. Structure, mechanism of action and regulation of pyruvate dehydrogenase. The coenzymes involved in the oxidation of pyruvate and in the Krebs cycle. Krebs cycle reactions and enzymes. Global reaction, energy yield and regulation. Biosynthetic role of the Krebs cycle. Role of the pentose pathway in the genesis of NADPH and sugars at 4, 5, 7 carbon atoms. Reactions and their regulation. Role of NADPH in metabolism.
Electron transport and oxidative phosphorylation The constituents of the respiratory chain: organization in complexes, redox potentials. The flavoproteins. Coenzyme Q. Cytochromes a, b, c. The respiratory chain: structure and function of complexes I, II, III and IV. Molecular mechanism of oxidative phosphorylation. Regulation of the respiratory chain and oxidative phosphorylation. Inhibitors of the respiratory chain and oxidative phosphorylation; decoupling agents. Transport of electrons from the cytoplasm to the mitochondrion (shuttle systems). Transport of the ATP formed in the mitochondrion. Other enzymes that use oxygen: oxygenase, oxidase, peroxidase. Mechanism of hydroxylation and role of cytochrome P450. Reactive oxygen species (ROS): chemical nature and biochemical mechanisms of cell damage. Enzymatic and non-enzymatic defense systems. Lipid metabolism Oxidation of fatty acids: function, activation, mitochondrial transport and beta-oxidation. Carnitine. Energy yield. Peroxisomal beta-oxidation; catabolism of unsaturated fatty acids, with odd number of carbon atoms and branched. Formation and fate of propionyl-CoA. Formation of ketone bodies and their use. Palmitate synthesis: reactions, enzymes and regulation. Elongation and unsaturation of acyls. Synthesis and degradation of triglycerides, phosphoglycerides and sphingolipids. Eicosanoid metabolism. Synthesis of cholesterol and its regulation. Cholesterol esters. Metabolism and role of bile acids. Transport of lipids in the blood. Classification, structure, function of plasma lipoproteins. Biochemical aspects of membrane transport. Metabolism of amino acids Protein digestion: protease, endo and exopeptidases. Intracellular degradation of proteins: lysosomal degradation and the ubiquitin system. Metabolic fate of amino acids. Essential amino acids. Transamination and deamination reactions and their role. Reaction and regulation of glutamate dehydrogenase. Decarboxylation of amino acids and polyamines. Metabolic fate of NH3. Reactions and regulation of the urea cycle. Correlation between the urea cycle and the Krebs cycle. Gluco and lipogenetic amino acids. The main coenzymes of nitrogen metabolism. Porphyrins. Synthesis and catabolism of heme. Formation of aminolevulinic acid and regulation. Biliary pigments (origin, conjugation and excretion). Metabolism of nucleotides and nucleic acids De novo synthesis of purine nucleotides: origin of the purine ring atoms; general reaction, energy demand and regulation. PRPP formation and its use in the synthesis of purine and pyrimidine nucleotides. Summary of the AMP and GMP from IMP. Adjustment. Phosphorylation reactions of purine and pyrimidine mono- and diphosphates nucleosides. Reuse of purine bases and nucleosides. Catabolism of purine nucleotides to uric acid. Synthesis of pyrimidine nucleotides: origin of the pyrimidine ring atoms, general reaction, energy demand and regulation. Catabolism of pyrimidine nucleotides. Synthesis of deoxyribonucleotides and its regulation. DNA: the DNA helix and the forces that stabilize it. Interactions between DNA and proteins. DNA replication in prokaryores and eukaryotes: enzymes involved and biochemical mechanisms that ensure the fidelity of replication. Types of RNA and their structure. Ribozymes and RNA catalysis. RNA synthesis (transcription) in prokaryotes and eukaryotes: RNA polymerase, general and specific transcription factors, co-activators. Post-transcriptional modifications of RNA (alternative splicing, RNA editing and regulation by microRNA). The turnover of RNA. Protein synthesis Enzymology and regulation of protein synthesis. RNA transfer and their aminoacylation. Interactions between ribosomes, mRNA, tRNA and soluble factors of protein synthesis. Speed and energy demand for synthesis. Acquisition of the three-dimensional structure. Modifications of the polypeptide chain after synthesis. Export of proteins.
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