Ateneo - UPO

Introduction to biochemistry and its relationship with other scientific disciplines. General features of living organisms and biological macromolecules. Chemical elements necessary for life and their abundance.
Fundamentals of thermodynamics. Open and closed systems. Enthalpy, entropy, Gibbs free energy and spontaneity of reaction, relationship between Gibbs free energy, energy coupling of reactions and overall energy of a thermodynamically unfavorable reaction. Strong and weak chemical bonds in biological molecules.
Biological molecules. Carbohydrates and lipids: classification, structure and general function. Amino acids, peptides and proteins. Proteins as informational molecules. Levels of protein structure, folding and proteostasis. Structural domains: definition and relationship with functional domains.
Structure-function relationship in proteins. Transport proteins; proteins with recognition and defense functions. Enzymes and enzymatic kinetics. Mechanisms of enzymatic regulation.
Methods for the study of proteins. Chromatographic, electrophoretic, immunological methods. Introduction to biocrystallography.
Introduction to biochemical reactions and bioenergetics. Molecules with high energy bonds. Electrons transporters.
Fundamentals of biosignaling: principles of signal transduction. Receptors, chemical mediators. Mode of release of signal molecules and the different types of signaling between cells. Characteristics of intracellular signaling pathways.
Co- and post-translational modifications of proteins with structural or informational function.
Structure and function of signal proteins: modularity of signal proteins, functional domains; production and role of second messengers.
Flux of molecules through biological membranes: electrochemical gradient and membrane potential, ion pumps. Facilitated passive diffusion: ion channels and transporters. Active transport.
Modules and components of intracellular signaling pathways. Calcium signaling; G proteins; the PI3K/AKT/mTOR pathway, the MAP-kinase pathway; protein kinase C; cytosolic tyrosine kinases belonging to the SRC family (SFK).
G protein-coupled receptors (GPCRs) and their signaling pathways. Glucagon and adrenaline signalling as examples of signal transduction downstream of GPCR. Biochemical mechanisms of sensory perception signaling: sight, smell, taste.
Tyrosine kinase receptors (TKR) and signaling pathways downstream of RTK. Insulin signaling.
Other signaling pathways. Receptors for cytokines and glycoprotein hormones; receptors belonging to the TNFR family. JAK / STAT pathway, NF-kB pathway. Serine and threonine receptor kinases: the TGF-β receptor family and downstream signaling pathways; integrins and focal adhesions. Receptors with cyclase guanylate activity. cGMP signalling

David L Nelson, Michael M Cox. Lehninger Principles of Biochemistry. Seventh Edition, 2017, Macmillan learning
Donald Voet, Judith G Voet, Charlotte W Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. 2016. John Wiley & Sons Inc.
Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter. Molecular Biology of the Cell. Sixth Edition, ISBN: 978-0-393-87094-7
Umberto Mura. ENZIMI IN AZIONE. EdiSES, 2012
Introduzione allo studio delle proteine. Duranti; Zanichelli

Transmit to the student the bases for a molecular approach to physiology and pathology, through the definition of the structure-function relationship of biological macromolecules, with attention to proteins with enzymatic activity, to transport proteins and to those involved in signal transduction. At the end of the course the student must be able to describe the molecular bases of macromolecules structures, the mechanisms of action of enzymes and an adequate knowledge of the mechanisms of signal transduction.

Basic knowledge of general chemistry, organic chemistry, physics and cell biology

Frontal lesson with the projection of slides, and movies. Execution of problems and quizzes in the classroom. Ability to run problems and quizzes at home via the moodle platform. Students can also use the recommended textbooks to deepen the topics discussed in the classroom

A pdf copy of the projected slides, the in-depth didactic material and all the information regarding the course and the exam procedures will be made available on the DIR.
The teacher is available, by appointment, to provide clarification on specific topics even outside of class time.

In itinere tests will be carried out during the course. These tests will NOT be used for final evaluation purposes but will allow the student to assess his level of understanding of the different topics and to practice for passing the examination.
The aim of the exam consists in verifying the level of knowledge of the program topics and the reasoning skills developed by the student. The exam consists of a written test including 50 questions related to all the topics covered during the course and including quizzes with multiple choice or true / false answers, recognition of molecular structures, and numerical problems. For each correct answer, 0.66 points are awarded. Sufficiency is reached by correctly answering to 27/50 questions. The evaluation is expressed in thirtieths (minimum mark 18, maximum 30 and honors). During the written test it is not allowed to consult any kind of material. The calculator is allowed. The examination allows to evaluate the critical sense, the ability to understand the text and the capacity to apply the logic and acquired specialized terminology to recognize and describe the biochemical processes (questions where it is required to make a choice between different alternatives) and the problem-solving skills by applying knowledge to the resolution of technical experimental problems (numerical questions).
Program and final text modality will be available on moodle DIR

1. Introduction to biochemistry
Definition of biochemistry and its relationship with other scientific disciplines. General features of living organisms. Principles of informational molecules and replication in natural polymers. Carbon, its properties and bonding versatility.
2. Fundamentals of thermodynamics
Enthalpy, entropy, Gibbs free energy and reaction spontaneity. Chemical bond.
3. Carbohydrates
Monosaccharides, stereoisomerism and chirality. Structural formula of the main aldoses and ketoses. Hemiacetals and hemiketals, mutarotation and anomers. Disaccharides, O-glycosidic bond. Polysaccharides: glycans, homopolysaccharides and heteropolysaccharides, energy reserve and structure; starch, glycogen, cellulose. Heteropolysaccharides: glycosaminoglycans. Glycoproteins: general notes and function. Lipopolysaccharides.
4. Lipids
General classification, general characteristics and function, standard nomenclature and alternative nomenclature. Saturated and unsaturated fatty acids, triglycerides, waxes. Phospholipids. Diseases associated with the metabolism of phospholipids. Glycolipids: classification, structure and function. Sterols, cholesterol and its derivatives: structure of stereoid hormones, bile acids.
5. Amino acids and peptides
Amino acids: structure, stereoisomerism and chirality. Modified amino acids. Isoelectric point. Peptide bond: primary, secondary, tertiary and quaternary structure of proteins. Concept of homology, conserved and non-conserved sequences, conservative and non-conservative mutations. Sequence alignment and "scoring" criteria, tools and online database for protein analysis.
6. Folding e proteosasi
Protein folding and denaturation, proteostasis. Thermodynamic of folding. Molecular chaperons. Pathogenic folding of proteins.
6. Structure-function relationship of proteins
Extracellular transport proteins, proteins that bind O2. The molecular basis of sickle cell anemia. Proteins with recognition and defense functions: immunoglobulins
7. Enzymes and enzymatic kinetics
Activation energy, reaction speed. Speed ​​constant. Enzymes: general mechanisms of action. Coenzymes: co-substrates and prosthetic groups. Classification of enzymes. Main catalysis mechanisms, enzyme kinetics. Michaelis-Menten equation. Representation according to Lineweaver-Burk. Definition of inhibitors
9. Methods for the study of proteins
Chromatography, electrophoresis, immunodiagnostic techniques. Introduction to biocrystallography.
10. Introduction to biochemical reactions and bioenergetics.
The transfer of groups in biochemical reactions: nucleophiles and electrophiles. Triphosphate nucleotides: molecules used for the transfer of chemical energy. Role of NTPs in biological reactions. The redox balance of the cell: structure and function of NAD, FAD, FMN, iron-sulfur groups, EME in catabolic and anabolic redox reactions.
11. Fundamentals of biosignaling - The principles of signal transduction
Receptors, ligands and downstream signalling pathways. The different types of signaling (endocrine, paracrine, iuxtacrine and autocrine). Mode of release of signal molecules: diffusion, secretion, release of extracellular vesicles.
12. Co- and post-translational modifications of proteins and signals for localization
Formation of disulfide bridges, gamma-glutammmylcarboxylation. Proteolysis, glycosylation, lipidation, GPI-linked proteins. Phosphorylation: effects on the structure of proteins. The human kinoma. Ubiquitination, acetylation and deacetylation and ADPribosylation; the sirtuins. Poly-ADPribosylation: PARP enzymes. Methylation and demethylation. Sulfation. Nitrosylation.
13. Structure and function of signal proteins
Modularity of signal proteins. General information on the structural organization of signaling molecules: recurrent domains and their functions. Protein-protein interaction domains: SH2, SH3, PTB, PDZ. Interaction domains with non-protein structures: PH, C1, C2, EF hand domains. The formation of signaling complexes; signalosomes and membrane lipid rafts. Production and role and of the second messengers.
14. Flux of molecules through biological membranes: channels and transporters
Electrochemical gradient and membrane potential. Passive diffusion facilitated: the transporters. The glucose transporters. Co-transport systems. Active transport: ion pumps. ATPase type P: Na + / K + pump; Ca pumps; ATPase type F and V. Active transport: ABC transporters Facilitated passive diffusion through ion channels: classification based on selectivity and regulation mechanism. Ion channels controlled by second messengers, lipids, mechanical stimuli and temperature. The Transient Receptor Potential (TRP) channels. The biochemical mechanism of synaptic signaling. Excitable cells and generation of action potential: neurotransmission, muscle contraction and secretion.
15. Signal transduction components: Calcium signaling
Calcium sensors: the EF hand domain. Calmodulin (CaM): structure and mechanism of action; examples of CaM-Ca2+-dependent signaling: CAMKII; troponin-tropomyosin complex in muscle contraction. The C2 domain and regulation of protein kinase C (PKC) activity. Other calcium effectors: the calpaines. Control mechanisms of intracellular Ca2+ concentration: SERCA ATPase and PMCA; NCX and NCKX ion exchangers; IP3-dependent Ca channel; the channel of the Ca type rianodina. Store Operated Channels (SOC).
16. Components of the signaling pathways: G proteins
The G proteins. The small G proteins: RAS, RAN, RAB, ARF, RHO families. Structure, regulation mechanism and main functions.
17. Intracellular signaling modules.
PI3K / AKT / mTOR pathway. MAP kinase pathway. Protein kinases C. Tyrosine kinases belonging to the SRC family (SFK).
18. G protein-coupled receptors (GPCRs) and their signaling pathways
Structure and mechanism of action of GPCRs and heterotrimeric G proteins. Heterotrimeric G proteins: mechanisms of action of the α and βγ subunits. Signaling glucagon and adrenaline as examples of signal transduction downstream of GPCR.
19. Biochemical mechanisms of signaling of sensory perceptions
Sight, smell, taste.
20. Tyrosine kinase receptors (TKR) and signaling pathways downstream RTKs
Tyrosine kinase with receptor function (RTK): structure and general signaling mechanism. Role of the interaction of SH2 / phosphotyrosine domains in the recruitment and activation of signal transduction pathways. Downstream signaling of RTK receptors: RAS and the MAP-kinase pathway, via PI3K-PKB / Akt-mTOR. Insulin signaling.
21. Other signaling pathways
Receptors for cytokines and glycoprotein hormones, receptors belonging to the TNFR family, JAK / STAT pathway, NF-kB pathway. Serine and threonine receptor kinases: the TGF-β receptor family; SMAD factors. Integrins and focal adhesions. Receptors with guanylate cyclase activity; signaling from cGMP

Be able to apply the acquired logic and scientific terminology for understanding and describing biochemical and cellular processes.
Be able to identify biological macromolecules, grasp the interconnections between macromolecular structures, function and regulation.
Autonomy of judgment in the evaluation of biochemical problems relative to the structure and functioning of biomolecules within the cell and in the extracellular environment
Knowledge about the mechanisms of enzyme activity and how to solve simple problems related to enzymatic kinetics.
Ability to predict the main biochemical events that occur downstream intercellular and cell and environment communication.
Capacity to understand how the main signaling pathways determine the phenotype of a cell.