84286 - METABOLIC BIOCHEMISTRY

Conoscenze e abilità da conseguire

Define the major pathways of intermediary metabolism of biomolecules, and discuss their bioenergetics, physiological adaptation, metabolic and main hormonal regulation, localization and cellular compartmentalization. Correlate the metabolic activity of tissues and organs with their function. Discuss how disruptions in intermediary metabolism may lead to disease, and illustrate with selected examples.

Contenuti

METABOLIC BIOCHEMISTRY

(6 CFU. Each lecture of 2 hours)

Lecture 1. INTRODUCTION TO METABOLISM.

Metabolic pathways. Steady state. Catabolism and anabolism. Coupling catabolic and anabolic pathways through adenyl nucleotides (ATP/ADP/AMP) and pyridine nucleotides (NAD(P)+ / NAD(P)H). Metabolism and cellular structure. Principles of metabolic regulation. ATP synthesis: substrate-level phosphorylation and oxidative phosphorylation. Utilization of ATP: orthophosphoric and pyrophosphoric cleavage.

Lecture 2. OXIDATIVE PHOSPHORYLATION (1).

General principles: converging reducing equivalents from metabolism to oxygen. Structure of the mitochondria. The mitochondrial respiratory chain: respiratory complexes and their cofactors (pyridine nucleotides, flavins, iron-sulfur clusters, Coenzyme Q, cytochromes, copper); respiratory supercomplexes; mechanism of electron transfer and proton translocation.

Lecture 3. OXIDATIVE PHOSPHORYLATION (2)

Chemio-osmotic coupling. ATP synthase and mechanism of ATP synthesis. Energy-linked reactions. Respiratory control, uncouplers. Uncoupling proteins. Generation of reactive oxygen species. Mitochondrial DNA (hints).

Lecture 4. OVERVIEW OF CARBOHYDRATE METABOLISM.

Structure of the main carbohydrates. Digestion and absorption. General scheme of carbohydrate metabolism in liver and extra-hepatic tissues. Blood glucose and its regulation.

Lecture 5. GLYCOGEN METABOLISM

Phosphorylation of glucose. Glycogen synthesis and glycogenolysis and their regulation in liver and muscle.

Lecture 6 GLYCOLYSIS (1)

Reactions of glycolysis, substrate-level phosphorylation, regulation.

Lecture 7. GLYCOLYSIS (2)

Re-oxidation of glycolytic NADH: lactate fermentation, aerobic oxidation (malate/aspartate shuttle and glycerol-phosphate shuttle). Energetic balance.

Lecture 8. PYRUVATE OXIDATION AND TCA CYCLE

Pyruvate oxidation: pyruvate dehydrogenase complex and its mechanism.

The tricarboxylic acid (TCA) cycle: reactions, substrate-level phosphorylation, regulation. The TCA cycle as a terminal metabolic pathway. Anaplerotic reactions: pyruvate carboxylase, mechanism and regulation. Biosynthetic role of the TCA cycle.

Lecture 9. GLUCONEOGENESIS

Gluconeogenesis: carbon and hydrogen sources; the reactions of gluconeogenesis. Regulation: hormonal control of glycolysis and gluconeogenesis in liver.

Lecture 10. PENTOSE PHOSPHATE PATHWAY (PPP)

The pentose phosphate pathway or pentose phosphate shunt: reactions and metabolic role: source or disposal of pentoses, reducing power for biosynthesis.

Lecture 11. HORMONAL REGULATION OF BLOOD GLUCOSE.

Hormonal regulation of blood glucose: insulin, glucagon, cortisol. Defects in glycaemia control: diabetes.

Lecture 12. OVERVIEW OF LIPID METABOLISM

Structure of the main lipids. Digestion, absorption and transport of dietary lipids. Role of bile salts. Lipolysis. Hormone-dependent triglyceride lipase. Non-esterified fatty acids (NEFA) in the blood.

Lecture 13. FATTY ACID OXIDATION

Beta-oxidation of fatty acids. Fatty acid activation. Transport to the mitochondrial matrix and role of carnitine. Steps of beta-oxidation. Oxidation of odd-chain and of unsaturated fatty acids. Energetics of fatty acids oxidation. Ketone bodies Fasting and ketogenesis: relation with gluconeogenesis. Steps of ketogenesis. Ketone bodies utilization.

Lecture 14. BIOSYNTHESIS OF FATTY ACIDS

Biosynthesis of fatty acids. De novo synthesis of palmitate, steps, energetics and reducing power. Regulation. Compartmentalization: role of citrate. Elongation and desaturation. Essential fatty acids and derivatives (ω3 and ω6 families).

Lecture 15. BIOSYNTHESIS OF LIPIDS

Biosynthesis of glycerol lipids: synthesis of phosphatidic acid. Synthesis of triacylglycerols and the major glycerophospholipids. Role of cytidine nucleotides. Hints on the synthesis of plasmalogens, sphingomyelin and glycolipids.

Lecture 16. BIOSYNTHESIS OF CHOLESTEROL

Steps of cholesterol biosynthesis: cytosolic acetylCoA, synthesis of mevalonate, formation of active isoprene (isopentenyl pyrophosphate), polymerization to squalene, and cyclization. Synthesis of cholesteryl esters and transport in lipoproteins. Derivatives of cholesterol: bile acids, Vitamin D3, steroid hormones. Other isoprenoid compounds. Regulation of cholesterol synthesis.

Lecture 17. METABOLISM OF PLASMA LIPOPROTEINS

Structure and classification of lipoproteins. Origin, composition and transport of the different lipoprotein classes.

Lecture 18. METABOLISM OF NITROGEN COMPOUNDS.

General scheme of nitrogen metabolism. Digestion of proteins and absorption of aminoacids . Essential aminoacids. Intracellular protein degradation. Deamination of aminoacids: Nonoxidative and oxidative deamination. D-aminoacid oxidase. Glutamate dehydrogenase. Trans-deamination. Mechanism of transaminase reactions. Pyridoxal phosphate.

Lecture 19. FATE OF AMMONIA

Ureotelic animals. Urea cycle: reactions and regulation. Fate of NH3 in extrahepatic tissues: glutamine synthesis and transport. Alanine cycle.

Lecture 20. FATE OF THE CARBON SKELETON OF AMINOACIDS

Gluconeogenesis. Glucogenic and ketogenic aminoacids. Relation with TCA cycle. Formation of acetylCoA: complete oxidation or lipogenesis. Aminoacid decarboxylation: biogenic amines. Polyamines.

Synthesis of non-essential aminoacids. Hints of reactions involved

Lecture 21. METABOLISM OF 1-CARBON UNITS

Metabolism of 1C units: role of FH4. Synthesis and catabolism of purine nucleotides and salvage patrhways. Synthesis of pyrimidine nucleotides. Synthesis of deoxyribonucleotides. Synthesis of thymidylate. Methionine and methyl group transfer. Role of vitamin B12.

Lecture 22. BIOSYNTHESIS AND CATABOLISM OF PORPHYRINS

Biosynthesis of heme. Heme catabolism and bilirubin transport. Jaundice. Concluding remarks on nitrogen metabolism.

Lecture 23. METABOLIC INTEGRATION

Interrelations between metabolic pathways. Interrelations between liver and peripheral tissues. Biochemistry of fasting and feeding conditions.

Lecture 24 . SPECIFIC METABOLISM OF SOME ORGANS AND TISSUES (HINTS)

An overview of specific aspects of metabolism in different organs an d tissues (brain, kidney, liver, skeletal muscle, heart, adipose tissue, blood).

Readings/Bibliography ibliography David L. Nelson and Michael M. Cox Lehninger Priciples of Biochemistry 7th Edition 2017 W.H. Freeman, New York Teaching methods Mainly regular lectures, alternated with quizzes and exercises during selected lectures. The slides of the presentations will be available on line before the lectures. *Attendance to this learning activity is mandatory;* the minimum attendance requirement to be admitted to the final exam is 66% of lessons. For Integrated Courses (IC), the 66% attendance requirement refers to the total amount of I.C. Students who fail to meet the minimum attendance requirement will not be admitted to the final exam of the course, and will have to attend relevant classes again during the next academic year. Professors *may* authorise excused absences *upon receipt of proper justifying documentation, in case of illness or serious reasons.* Excused absences do not count against a student’s attendance record to determine their minimum attendance requirement / Assessment methods Final exam: the detailed modalities of the cumulative written test of the integrated course "Signalling Pathways in Health and Disease" are given in the site of Maria Luisa Genova. / Teaching tools Lecture slides will be available on line before the lecturesCollegamento del programma dell’insegnamento con i 17 Obiettivi per lo Sviluppo Sostenibile dell'ONU

L’Agenda 2030 per lo Sviluppo Sostenibile è un programma d’azione per le persone, il pianeta e la prosperità, sottoscritto nel settembre 2015 dai governi dei 193 Paesi membri dell’ONU. Essa propone 17 Obiettivi per lo Sviluppo Sostenibile - Sustainable Development Goals, SDGs - in un grande programma d’azione per un totale di 169 traguardi o ‘target’. L’avvio ufficiale del programma, teso al raggiungimento degli Obiettivi per lo Sviluppo Sostenibile, ha coinciso con l’inizio del 2016 e guiderà i Paesi che lo hanno sottoscritto sulla strada da percorrere per i prossimi 15 anni (2030). Gli SDGs danno seguito ai risultati degli Obiettivi di Sviluppo del Millennio (Millennium Development Goals), che li hanno preceduti, e rappresentano un impegno comune e condiviso su aspetti fondamentali per uno sviluppo sostenibile come, ad esempio, la lotta alla povertà, l’eliminazione della fame ed il contrasto al cambiamento climatico. ‘Obiettivi comuni’ significa che riguardano tutti i Paesi e tutti le persone: nessuna ne è esclusa, né deve essere lasciata indietro, lungo il cammino necessario per portare il mondo sulla strada della sostenibilità.

Con l’adozione del Piano Strategico 2016-2018 i 17 SDGs sono entrati a far parte del Piano Strategico dell’Alma Mater Studiorum - Università di Bologna. Al fine di valutare il contributo dell’Ateneo al raggiungimento dei 17 Obiettivi di Sostenibilità, si chiede, ove fosse presente un collegamento diretto e prevalente dei contenuti dell’insegnamento con i temi degli SDGs di seguito illustrati, di selezionarne uno o più (massimo 4). Per ciascun obiettivo prescelto è necessario precisare tra gli argomenti suggeriti dall'UNESCO nel documento "Educazione agli Obiettivi per lo Sviluppo Sostenibile [https://www.unibo.it/uniboweb/resources/people/documents/ObiettiviSviluppoSostenibile.pdf] ", quelli trattati nel proprio insegnamento.

Una volta effettuata la selezione, nella pagina web dell’insegnamento comparirà l’icona corrispondente agli SDG’s selezionati.

Orario di ricevimento

Consulta il sito web di Giorgio Lenaz

Consulta il sito web di Michele Di Foggia