00061 - Biochemistry (B)

Learning outcomes

The biochemistry course allows the student to acquire the knowledge of the essential elements of the intermediate metabolism of the main biological molecules (carbohydrates, lipids and nitrogenous compounds), their interrelationships, their metabolic and hormonal regulations, and the cellular localization and compartmentalization of the main metabolic pathways; the specialization of the various human organs and tissues in metabolic activities as a prerequisite for the knowledge of their specific functions; the molecular mechanisms of regulation of cellular activity with particular regard to intracellular signal transduction mediated by hormones, neurotransmitters and other extracellular messengers; the biochemical principles which underlie human nutrition with particular regard to the molecular mechanisms of digestion and absorption of nutrients and essential nutritional principles with references to nutrigenomics.

Course contents

This course is part of the Integrated Biochemistry Course. Upon completion of the Integrated Biochemistry Course, students will acquire the essential molecular knowledge needed to study human physiology and pathology.

SPECIFIC COURSE CONTENT:

Introduction- general aspects of cell structure and thermodynamic aspects of metabolism of the cell and animal organisms.

Bioenergetics - laws of thermodynamics and Gibbs equation - free energy and chemical potential - DG' and DG'°: relationship of DG'° with the equilibrium constant - coupled reactions - high energy compounds - - ATP and its central role in metabolism - mechanisms at the basis of ATP-driven reactions - redox reactions and redox potentials (E' and E'°) - relationship between DG (DG'°) and DE (DE'°).

Proteins - structural organization: primary, secondary, tertiary and quaternary structure - structural characteristics and functional role of fibrous and globular proteins - thermodynamics and kinetics of polypeptide chain folding - protein denaturation.

Oxygen carrier proteins: structure of the prosthetic heme group- structural characteristics of myoglobin-oxygen binding curve and biological function of myoglobin - structural characteristics of hemoglobin - oxygen binding curve and positive cooperative mechanism of oxygen binding - Biological function of hemoglobin- allosterism and allosteric effectors (Bohr effect) of hemoglobin.

Enzymology classification of enzymes - enzymatic cofactors - chemical equilibrium and kinetics of a chemical reaction - free energy diagram of a reaction: activation energy and transition state - mechanism of action of enzymes - mechanisms and catalytic strategies - Michaelis and Menten kinetics - irreversible and reversible inhibitors - effect of pH and temperature on enzyme activity - -mechanisms of regulation of enzyme activity: covalent modification - proteolytic activation - allosterism.

Lipid Metabolism The main roles of lipids: storage of fats and essential components of membranes. Compartmentation of lipid metabolism in the body. Role of plasma lipoproteins.

Lipid catabolism. Lipolysis: hormone-dependent lipase and NEFA. Beta-oxidation of fatty acids: reactions, compartmentalization, energy yield. Beta-oxidation of saturated and unsaturated fatty acids. Synthesis of ketone bodies. Metabolic acidosis and keto-acidosis. Metabolic relationships between ketogenesis and gluconeogenesis.

Lipid biosynthesis Transport of Acetyl-CoA from the mitochondrion to the cytosol. Malonyl-CoA synthesis reaction. Palmitate biosynthesis. Hormonal and allosteric regulation of palmitate biosynthesis. Biosynthesis of saturated and unsaturated fatty acids. Biosynthesis of TAGs and general aspects of the biosynthesis of phospholipids. Metabolic cycle of TAGs and regulation by Cortisol. Cholesterol biosynthesis. Regulation of cholesterol biosynthesis.

Membrane permeability and transport. Kinetic and thermodynamic aspects of solute transport. Channel proteins and facilitated diffusion of solutes. Primary and secondary active transport.

General aspects of hormones and other extra-cellular messengers Classification of hormones. Biosynthesis, secretion and plasma transport of hormones. Hormone receptors. Fundamental aspects of the biochemical-physiological action of different hormones. Neuroendocrine system.

Signal transduction mediated by membrane receptors Heterotrimeric G protein coupled receptors (GPCR): cyclic AMP, Diacylglycerol, Inositol 1,4,5-trisphosphate and Ca2+ as intracellular messengers. Structural and functional characteristics of G proteins. Mechanisms of switching off the signal transduction pathways. Insulin and growth factor receptors: Ras protein/MAP kinase and Phosphatidylinositol 3-kinase (PI3K) pathways. Cytokine receptors: Jak/Stat pathway. Cyclic GMP and nitric oxide. Ionotropic and Metabotropic Receptors. Onset and transmission of nerve impulses.

Signal transduction mediated by intracellular receptors Cytosolic/nuclear receptors and response elements to lipophilic hormones.

Biochemical aspects of specific hormones. Molecular and metabolic effects of hormones that regulate tissue metabolism. Modulation and coordination of tissue metabolism in the human organism.

Readings/Bibliography

D.L.Nelson, M.M.Cox. "I principi di Biochimica di Lehninger". VIII ed., Zanichelli

Lieberman M., Marks A.D. "Marks-Biochimica Medica:un approccio clinico. Seconda edizione, Casa Editrice Ambrosiana.

Salvatore F. "Biochimica Umana", Casa Editrice Idelson-Gnocchi.

Teaching methods

Regular lectures

Assessment methods

The Biochemistry exam consists of an interview held by the student with the teachers of the course itself. Each teacher expresses his/her assessment through a grade, based on the ability demonstrated by the student to present specific topics in a concise, accomplished and critical way in the field of glucose metabolism, mitochondrial bioenergetics, nitrogen metabolism, lipid metabolism, hormones-neurotransmitters and signal transduction, and nutritional biochemistry. The various partial grades, in proportion to the number of credits, contribute to the Biochemistry grade.

Graduation of the final grade:

Mediocre preparation and on a limited number of topics covered in the course → sufficient/mediocre assessments;

Good level of preparation on various topics covered in the course and good ability to carry out an in-depth analysis and connections between different aspects of the topics discussed → fair/good evaluations);

Exhaustive preparation on the topics covered in the course, excellent ability to carry out an in-depth analysis and connections between different aspects of the topics discussed, and mastery of the specific terminology → very good/excellent evaluations

Before taking the oral interview of Biochemistry, the student must take and pass the written test of General Biochemistry. The grades obtained in the test of General Biochemistry and in the oral interview of Biochemistry contribute to the definition of the Biochemistry I.C. grade. According to the teaching rules, the BIOCHEMISTRY exam, like all those of the 1st year of the Medicine and Surgery Course, must be passed before the student faces the exams of the 4th year and of the following years.

Teaching tools

- Regular lectures for insights and explanations.

-Multimedia laboratories of metabolic biochemistry to deepen aspects related to the metabolism and the mechanisms of regulation of cellular activities through the transmission of extra-cellular signals.

Office hours

See the website of Alessandra Baracca