A theoretical study on the mechanism of the oxidation of substrates by human aromatase enzyme (CYP19A1)

• Autores: Ignacio Viciano Gonzalo
• Directores de la Tesis: Sergio Martí Forés (dir. tes.), Raquel Castillo Solsona (codir. tes.)
• Lectura: En la Universitat Jaume I ( España ) en 2016
• Idioma: inglés
• Tribunal Calificador de la Tesis: Slawomir Berski (presid.), María Teresa Roca Moliner (secret.), Aurélien de la Lande (voc.)
• Programa de doctorado: Programa Oficial de Doctorado en Química Teórica y Modelización Computacional
• Materias:
  • Física
    • Química física
    • Física teórica
  • Química
    • Bioquímica
      • Enzimología
      • Biología molecular
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • The enzyme Cytochrome P450 aromatase plays an essential role in the biosynthesis of estrogens, and its inhibition is an important target for the development of drugs for the treatment of breast cancer. The main purpose of the present thesis is to improve the understanding of the catalytic mechanism and the biochemistry of this enzyme from the standpoint of theoretical chemistry. The results of this thesis have been divided into three main sections: (1) Study of the reactive species of the enzyme aromatase: Compound I; (2) Study of the hydroxylation of the natural substrate androstenedione, during the first catalytic subcycle of the enzyme aromatase; and (3) Study of the hydroxylation of Exemestane, an esteroidal third generation aromatase inhibitor, currently used in hormone dependent breast cancer therapy.