20402204 - BIO-ORGANIC CHEMISTRY

The course will address the chemical transformations shared by organic chemistry and biological systems. indeed, although the functional group elaborations are formally the same, the followed reaction pathways result to be quite different with respect to the experimental conditions of both organic syntheses and biological processes.
In such a context, the enzymatic action modes in living systems will be compared with the key role performed by temperature, pressure, ph, catalysts and solvents.
Keeping this in mind, a few of the most well-known chemical reaction mechanisms will be studied, underlining, step by step, the main similarities and distinctions with the analogous biological transformations.

GASPERI TECLA

teacher profile | materiale didattico

Mutuazione: 20402204 CHIMICA BIOORGANICA in Biologia per la ricerca molecolare, cellulare e fisiopatologica LM-6 N0 GASPERI TECLA

Programma

Cultural skills (Knowledge of): The course aims to provide students with the chemical basis of the structure, the properties, and the reactivity of biological molecules, as well as the main notions for understanding the logic that regulates bio-organic chemistry processes.
Methodological skills (How to carry out): at the end of the course, the student will be able to analyze and discuss the catalytic mechanism of the most important classes of enzymes, as well as to understand the importance of the organic chemistry applied to the study of biological systems, to biocatalysis, and to the development of biologically active molecules.
Introduction to Bio-organic Chemistry (A short overview of the most common functional groups involved in biological processes, highlighting their main features).
Organic chemistry mechanisms to explain key steps in pivotal biological pathways:
• Electrophilic Addition Reactions:
 regioselective epoxidation of alkenes; the action of squalene epoxidase in squalene/lanosterol transformation.
• Nucleophilic Substitution Reactions
 bimolecular Nucleophilic Substitution Reaction (SN2): the S-adenosylmethionine (SAM) role in the methyltransferase-catalyzed reactions;
 carbocation chemistry in the nucleophilic substitution reaction (SN1): the IPP isomerase.
• Elimination reactions:
 β-elimination reaction and the enolase role in the synthesis of the phosphoenolpyruvate (PEP).
• Nucleophilic Carbonyl Addition Reactions
 imine and enamine formation; how Schiff bases act in the PLP-dependent enzymatic catalysis;
 acetals and sucrose synthase;
 Michael additions and the histidine ammonia-lyase function.
• Isomerization and epimerization:
 keto-enol tautomerism and ribose-5-phosphate isomerase catalysis;
 Inversion and retention of the stereochemical configuration: the glucosidase mechanism.
• Carbonyl condensation reactions:
 aldol condensation promoted by aldolases (classes I and II)
 Claisen condensation and the acetyl synthase function in the fatty acids synthesis.
• Acyl Nucleophilic Substitutions:
 the hydrolysis of esters and the mechanism of Human Pancreatic Lipase;
 esterification reactions and the synthesis of triacylglycerols by means of acyl-CoA synthetase and acyltransferase;
 amide bond formation; asparagine synthetase vs glutamine synthetase;
 the hydrolysis of amides and the chymotrypsin action mode.
• Oxidations and reductions
 metal hydride and the reduction of the ketone carbonyl group in acetoacetyl ACP due to the β-keto thioester reductase;
 Baeyer-Villinger oxidation and the hydroxyacetophenone monooxygenase;
 ozonolysis reactions and dioxygenase enzyme activity.
• Carboxylation reactions:
 Grignard reactions in CO2 atmosphere; mechanisms of both the pyruvate carboxylase and Ribulose-1,5-bisphosphate carboxylase oxygenase (RuBiscO);
 the decarboxylation reaction in both malonic and acetoacetic synthesis; the key role of thiamine pyrophosphate (TPP) in the 1-deoxy-D-xylulose 5-phosphate synthase catalysis.
• Noteworthy examples: pyruvate dehydrogenase complex, the kynurenine catalysis and the tryptophan metabolism; anomalous features in histidine metabolism.


Testi Adottati

John McMurry, Tadhg Begley in “Chimica Bio-Organica”, Zanichelli Ed. spa
T.W. Graham Solomons; Craig B. Fryhle in “Organic Chemistry”, 10th Edition, Wiley.
John McMurry in “Chimica Organica”, Piccin-Nuova Libreria
Bruno Botta in “Chimica Organica” Edi-ermes

Lecture notes and bibliographical references will be provided


The teacher receives Tuesday from 17.00 to 19.00 by appointment via e-mail: tecla.gasperi@uniroma3.it


Modalità Erogazione

The course mainly involves lectures and few laboratory sessions, during which some key transformations will be both carried out in the presence of enzymes and performed with the classic chemical reagents.

Modalità Valutazione

The oral exam consists in the presentation (by slide projection) of an enzyme of student’s choice, of which the student will have to illustrate the structure, the main characteristics and the mode of action; this presentation will then be discussed with the teacher comparing the purely chemical aspects with the biological behaviour.