MedInTO Medicine and Surgery

Biochemical and molecular basis of metabolism

Biochemical and molecular basis of metabolism

Academic year 2017/2018

Sommario del corso

• Course objectives
• Results of learning outcomes
• Course delivery
• Learning assessment methods
• Support activities
• Program
• Suggested textbooks and readings
• Teaching tools

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 represent the core of the program as a paradigmatic example to understand life at a mechanistic level. The key concepts under study 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.

The 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 to 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 and 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.  

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), an accompanying active learning part will be accomplished both in the classrooms and on-line, based on the Moodle platform. Simple molecular design and modeling is performed on-line using JME and JSMol. Introductory use of biological databases are 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

The exam will be based on a test, which is normally administered on the Moodle platform. The test will include multiple-choice questions, exercises and open questions, covering all the topics in the syllabus. A total of about 50  questions, with  30 points related to biochemistry and 20 to molecular biology, will constitute the test. 

An oral discussion can follow in two conditions: 

• at the specific request of the student anytime He/She feels the need to improve the final score (if equal or above 18). 
• at the specific request of the teachers anytime  they need to clarify issues arising from the written test.  

The oral can increase or decrease the final score of the exam.

The exams will be performed in class only

Support activities

A number of optional activities are available on the Moodle Platform (http://medicina.i-learn.unito.it/), concerning further exercises on molecular structures, and verification quizzes at the end of each part (or Chapter)..

Program

Metabolic Biochemistry

Metabolism.

• Introduction to mechanisms of regulation of metabolic pathways. The metabolome.

Vitamins and cofactors.

Review of catalytic mechanism  by enzymes involved in energy extraction from food

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.

• metabolis of alcohol 

Metabolisms as molecular networks

• Basics of the graph theory

• Circuits and Networks

• Metabolic networks.

• Interaction between macromolecules: protein-protein, protein-DNA, protein-RNA, RNA-RNA.

• Methods to assess molecular interactions.

• Analysis of protein-DNA interaction and chromatin accessibility on a global scale

.

Special topic biochemistry

Steroid Hormones 

• Classes of Steroid Hormones

• Biosynthesis steroid hormones

Food digestion 

• Digestion, Absorption, and Transport of Carbohydrates

•  Digestion and Transport of Dietary Lipids 

• Protein Digestion and Amino Acid Absorption 

Metabolism of the central nervous system 

• Introduction

• Compartmentalization of metabolism

• Relations between glucose and ketone bodies in development 

• brain glucose and  glycogen

• Metabolism of neurotransmitters

• damage from cerebral ischemia reperfusion

• metabolic encelopathies 

Overview of metabolism in cancer cells 

Genomic Regulation

• Genome expression, regulation and control in development, homeostasis and disease.

• Global analysis of gene structure and expression.

• Epigenetic control of the genome

• Networks of transcriptional and post-transcriptional control of gene expression.

• microRNA, lncRNA and their role in the circuits controlling acute, damped, homeostatic and cyclic responses. Other roles of lncRNAs.

Functional genomics.

• The genome projects and their functional significance: ENCODE, GWAS, TCGA, 1000 Genomes and others.

• Biological databases. Primary and secondary databases. Knowledge databases.

• Reference database for medicine. OMIM, TCGA, and other databases of interest.

• Tools for network and pathway analysis and visualization..

Biochemistry, 5th edition Jeremy M Berg, John L Tymoczko, and Lubert Stryer.New York: W H Freeman; 2002.

Nelson, D.L., Lehninger, A.L. and Cox, M.M., 2008. Lehninger principles of biochemistry. Macmillan.

Molecular Biology Scientific Reviews Provided as Reference Materials on the Moodle Platform: http://medicina.i-learn.unito.it/course/view.php?id=104 . Online presentations of database purpose, structure and content are available as "guides" or "help" or "tutorials"  on Database websites.

• Teaching materials
• Exams and finals
• Go to Moodle
• Visit the forums