Medicine and Surgery

Lessons will follow the sequence of subjects as reported in the program. At the beginning of each week, subjects of the following week will be indicated. Introduction to metabolism: intermediary metabolism; homeostasis and steady-state. single-step vs multistep pathways. Catabolism and anabolism. Possible interconversions of the three major metabolic fuels in humans. Types of metabolic pathways: linear, cyclic, spiral. The phosphate group-transfer potential. The flow of phosphoryl groups from high-energy phosphate donors, via the ATP-ADP system, to low-energy phosphate acceptors. Principles of bioenergetics. Energy and its conservation: first and second law of thermodynamics. ATP and its role in metabolism. Carbohydrate metabolism. Absorption and digestion. Lactose intolerance. Entrance of glucose in the cell: the GLUT transporters and their role in the maintenance of glucose homeostasis. Glycolysis (all the steps): Preparatory phase (I) and payoff phase (II). Alternative fates of pyruvate. Feeder pathways for glycolysis (from fructose, mannose, galactose and glycogen). Detailed catalytic mechanism of aldolase and phosphoglycerate mutase. Fructose 2,6-bisphosphate as allosteric modulator of glycolysis and gluconeogenesis. Hormonal regulation. Metabolism of fructose. Metabolism of galactose. Lactate fermentation. Cori cycle. Glycolisis and cancer: Warburg effect. Gluconeogenesis (all the steps) and substrates feeding it. Alanine cycle. Pyruvate carboxylase catalytic mechanism. The anaplerotic reactions which replenish depleted TCA cycle intermediates. Glucose 6-phosphate phosphatase. regulation of gluconeogenesis The pentose phosphate pathway : the 4 modes of action. Regulation. Oxidative phase and non-oxidative phase (all the steps). Pathways requiring NADPH. Cytochromes P450: mitochondrial and microsomal. NADPH in NO production. Role of G6PDH in erythrocytes, in the detoxification from ROS. Glutathione reductase and peroxidase. G6PDH deficiency Synthesis and degradation of glycogen. Glycogenin. Glycogenolysis: glycogen phosphorylase and PLP role in its mechanism. Branching and debranching enzymes. Hormonal regulation and physiological implications. Glycogen Storage Diseases: von Gierke, McArdle and Pompe disease. Oxidation of pyruvate and acetyl-CoA. Citric acid cycle (all the steps). Pyruvate dehydrogenase: coenzymes and role of E1, E2 and E3 enzymes. PDH deficiency. Arsenic poisoning. Cytosolic and mitochondrial aconitase. Isocitrate dehydrogenase catalytic mechanism. The malate-aspartate and glycerophosphate shuttle systems. Electron transport and oxidative phosphorylation. Respiratory chain: complex I-IV and chemiosmotic theory. ATP synthase. Inhibitors and uncouplers. Energetic yield of carbohydrate and lipid catabolism. Oxidative phosphorylation: energy-transducing membranes, chemiosmotic theory, Mitchell’s postulates, primary & secondary proton pumps, uncoupling agents (ionophores and protonophores). Bacteriorhodopsin. Mitochondrial DNA. Coenzyme Q. The mitochondrial respiratory chain, complex I-V (main prosthetic groups). Respiratory inhibitors. Structure of complex III and Q cycle. ATP synthase structure, essentials of the rotary mechansm. Lipoproteins, detail of structure and metabolism. Fatty acid oxidation. Carnitine shuttle and mitochondrial beta oxidation of both even and odd number of fatty acids. Beta oxidation in the peroxisome. Ketone bodies metabolism. Regulatory mechanisms. Fatty acid synthesis. FAS complex and subunit enzymatic activities. Elongation and desaturation. Synthesis of triglycerides and phopsholipids. Strategy I and II. Sphingosine biosynthesis. Triglyceride synthesis and triacylglycerol cycle. Glyceroneogenesis. Cholesterol synthesis and of its derivatives. Nitrogen metabolism. Principle of N homeostasis. Digestion of exogenous proteins and absorption of aa. Transamination and PLP-depend mechanism of transamination (detailed mechanism). PLP and racemization and decarboxylation. Transdeamination: Glutamate dehydrogenase. Urea cycle. Regulatory mechanisms. Biosynthesis of biological amines (neurotransmitters: adrenaline, dopamine, serotonin) Detailed metabolism of phenylalanine, cysteine, methionine. SAM and methylation reactions (synthesis of creatine and NOS). Degradation of endogenous proteins. UPS and autophagy. Hormones: structure, synthesis and function mainly focused on metabolism. Hypotalamic-pituitary axis. Hypotalamic releasing factors. Neurohypophysis hormones: oxitocin and vasopressin. Anterior pituitary hormones: growth hormone, prolattin, tyroid-timulatin hormone, adrenocorticotropic hormone, follicle stimulatin and luteinizing hormones. Tyroid hormones. Paratyroid hormone, calcitonin and vitamin D. Calcium metabolism. Pancreatic hormones: insulin and glucagon. Adrenal gland hormones: cortisol and aldosterone. Medullar hormone: adrenalin. Sexual hormones: testosterone and estrogen. Local hormones: eicosanoids and nitric oxide.

In order to sit the exam, the student must have passed Chemistry and Introduction to Biochemistry (mandatory) as well as the Biochemistry I progress test. In case of failure in the Progress test the student will be admitted to sit the Biochemistry exam and examined on the whole programme (I and II) as oral exam, preceded by a pre-test (mandatory).

David L Nelson, Michael M Cox - I principi di biochimica di Lehninger- Sesta edizione- Zanichelli Textbook of Biochemistry with Clinical Correlations, Thomas Devlin EdiSES

Formal Lectures and learning tests (to assess in an informal way the learning during the teaching Subject of the lessons will follow the sequence as reported in the program. At the beginning of each week, subjects of the following week will be indicated.

Mandatory attendance

To Pass the test student must obtain a note of 18/30 for each subject of the integrated teach. Student must possess a sufficient knowledge of the program. To obtain a note of 30/30 with distinction student must possess an excellent knowledge of the whole program using a correct terminology to expose the topics. The written examination is a multiple choice test on Biochemistry 1 and 2 subjects. Students who passed the Biochemistry 1 test will respond only to the Biochemistry 2 questions. The oral examination for the entire course of Biochemistry II will assess the following: 1) student's knowledge of metabolic pathways dealt with in detail during the course, their points of control and the associated pathologies; 2) role of specific hormones in the global control of anabolism and catabolism at the level of the whole organism or specific tissues; 3) mechanisms of signal transduction and the inter-connections between the different metabolisms; 4) ability to write chemical structures of compounds involved in metabolism.

Formal Lectures and learning tests (to assess in an informal way the learning during the teaching Subject of the lessons will follow the sequence as reported in the program. At the beginning of each week, subjects of the following week will be indicated.