MedInTO Medicine and Surgery

Biochemical and Molecular Basis of Metabolism

Biochemical and Molecular Basis of Metabolism

Academic year 2024/2025

Sommario del corso

• Course objectives
• Results of learning outcomes
• Program
• Course delivery
• Learning assessment methods
• Support activities
• Suggested readings and bibliography
• Notes
• Teaching Modules
• Teaching tools
• Course card

Course objectives

The program aims to introduce students to the biochemical basis necessary to deal effectively with medical problems. In particular, the production of energy and its use represents the core of the program as a paradigmatic example to understand life at a mechanistic level. The key concepts understudy will focus on how complex molecules that are found in living organisms create structures, carry out chemical reactions, and store and use the information to generate the remarkable properties of living organisms. Metabolism is also a key level in which a myriad of interactions between molecules illustrate the concepts of living cells and organisms as complex systems.

Biomedical knowledge is increasingly organized today in databases and knowledge repositories, spanning from genomics to metabolomics and pharmacogenomics. Consequently, the awareness of the biomedical data available and basic bioinformatic tools to deal with data is an absolute requirement in any Medicine curriculum, in order to guarantee the ability to access certified, robust and constantly adjourned information. This will be spent in many other courses in the following years.    

Results of learning outcomes

At the end of the course, the student will have an in-depth knowledge of the chemical processes that extract energy from cells. Moreover, the student will mature the ability to observe biological phenomena and think of them as the result of complex interactions between single molecules. As a future MD, the student will be eager to search for disease-causing errors within this network of interactions and think of drugs as agents that can restore the physiological status.   

In addition, the Student will be able to obtain basic information on genes and proteins and how they are interacting at a network level, by interrogating the most common genomic and biomedical databases. This ability will be gained through tutored and autonomous bioinformatic activities in the computer room.

Program

• Metabolic Biochemistry
• Metabolism:
  • Introduction to mechanisms of regulation of metabolic pathways;
  • The metabolome.
• The metabolism of carbohydrates:
  • Glycolysis;
  • The metabolism of glycogen in the liver and muscles;
  • The citric acid cycle;
  • Electron transport, oxidative phosphorylation and regulation of ATP production;
  • Pentose phosphates;
  • Gluconeogenesis;
  • Digestion of carbohydrates;
  • Utilization of galactose, fructose, mannose;
  • Genetic diseases related to carbohydrate metabolism;
  • Regulation of carbohydrate metabolism by hormones and transcriptional circuits
• Lipid metabolism:
  • The oxidation of fatty acids;
  • Biosynthesis of fatty acids;
  • Biosynthesis of phospholipids;
  • Biosynthesis of cholesterol and bile acids;
  • Prostanoids;
  • Regulation of lipid metabolism by hormones and transcriptional circuits;
  • The production and the effects of oxygen radicals.
• Nucleic acid metabolism:
  • Purine biosynthesis;
  • Pyrimidine biosynthesis;
  • Purine catabolism;
  • Pyrimidine catabolism;
  • Genetic diseases related to nucleotide metabolism;
  • Regulation of nucleotide metabolism.
• Protein metabolism:
  • The anabolic pathways of nitrogen;
  • Nitrogen fixation;
  • The synthesis of glutamate, glutamine, carbamoyl phosphate;
  • Paradigmatic examples of synthesis of amino acids: alanine, aspartate, cysteine, tyrosine;
  • The urea cycle;
  • The metabolism of heme.
• Integration of metabolism:
  • Overview of metabolism connections and separation in the body;
  • The metabolism during stress, aerobic and anaerobic activity;
  • Metabolism of alcohol.
• Special Topics Biochemistry
  
  • Biochemistry of the central nervous system

Molecular Biology & Bioinformatics

• Proteins in Metabolism:
  

  • Metabolic networks and pathways

  • Qualitative and quantitative regulation of enzymes;

  • Protein, enzymes, network databases;

  • Tools for network and pathway analysis and visualization

• Genes:
  

  • The genome projects and their functional significance: evolution of DNA sequencing technology.

  • The genome database and browsers: principles of accessing data in NCBI, ENSEMBL.

  • Organization of genes in the Human genome. Structures of genes, transcript isoforms. Accessing the sequence.

• Genomic regulation:
  

  • Transcription factors and recognition of DNA seqeunces

  • Database of Transcription Factor Binding Sites.

  • Different types of gene promoters, proximal pausing.

  • Transcription and post-transcriptional modifications of RNA, splicing and alternative splicing. Metabolism of noncoding RNAs

  • Diseases linked to splicing and intervention by RNA-based drugs.

  • RNA Editing, methylation, transport and RNA decay. RNA binding proteins.

  • Proteins synthesis: RNA translation-codon usage.

  • Post-transcriptional regulation: RBP, regulation of alternative splicing. Micro RNAs.

• Analysis of RNA expression

  • Gene expression analysis. Genome-wide technologies: micorarrays and RNA-seq.

  • Gene expression databases. Featuring the roles of gene expression profiles: The Gene Ontology resource.

• Epigenetic regulation.

  • DNA methylation and Histone PTMs. Writers, erasers and readers.

  • Analysis of protein-DNA interaction and chromatin accessibility on a global scale. Databases of chromatin-interacting proteins.

  • Epigenetic inheritance, programming and reprogramming.

  • The key role of enhancers and different types of Transcription Factors.

  • Signal-dependent transcription Factors

  • Monoallelic expression and genomic imprinting.

• Qualitative variation and expression regulation in Medicine.

  • Human Genetic Variation: The 1000 Human Genome project, GWAS, TCGA and other large-scale genome projects.

  • Methods for variant prioritization.

  • Reference database for medicine: OMIM and other databases of interest;

  • Metabolism regulates gene expression. The circadian rhytms of genes.

  • Complex Biomarkers for human diseases: Quantitative gene expression, other Omics data.  

  • Gene cloning, gene expression in cells and animals; retroviral vectors; the CRISPR-Cas technologies.

Course delivery

Teaching is organized in both lectures and active learning parts. Lectures will accomplish for a total of 122 hours. For each Lecture package (6-8 hours), and accompanying active learning part will be accomplished both in the classrooms and online, based on the Moodle platform. Simple molecular design and modelling are performed online using JME and JSMol. Introductory use of biological databases is exercised using the NCBI and ENSEMBL websites. Knowledge databases as NCBI Gene, Gene Ontology, GEO, are used to recover information on specific components of simple metabolic pathways. Network and pathway analytical tools as those offered in KEGG, Wikipathways, REACTOME, are used to describe examples. Finally, specific examples of metabolic pathway alterations are explored using OMIM, TCGA and other phenotype-genotype databases.

Learning assessment methods

Support activities

A number of optional activities are available on the Moodle Platform (Moodle site), concerning further exercises on molecular structures, and verification quizzes at the end of each part (or Chapter).

• Molecular Biology Scientific Reviews Provided as Reference Materials on the Moodle Platform: https://elearning.unito.it/medicina/course/index.php?categoryid=2781
• Online presentations of database purpose, structure and content are available as "guides" or "help" or "tutorials"  on Database websites.

Notes

Students with DSA or disabilities are kindly requested to take note of the reception services and support services offered by the University of Turin, and in particular of the procedures required for exam support.

Teaching Modules

• Biochemical and Molecular Basis of Metabolism - Module of Biochemistry (SCB0314C)
• Biochemical and Molecular Basis of Metabolism - Module of Bioinformatics (SCB0314D)
• Biochemical and Molecular Basis of Metabolism - Module of Molecular Biology 1 (SCB0314A)
• Biochemical and Molecular Basis of Metabolism - Module of Molecular Biology 2 (SCB0314B)

• Teaching material
• Exams and finals
• Class schedule
• Go to Moodle
• Register for the course
• Enrolled students
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