Università Roma Tre

Contents
Introduction to Bioorganic Chemistry (A short overview about 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 phosphoenol pyruvate (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 the 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 hystidine metabolism.

Moreover, there will be a number of practical experiences, during which few enzymatic transformations will be compared with the corresponding chemical reactions.

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