Abstract

GRAZIANO, Martín; CARCAGNO, Abel Luis; ROMERO, Delfina Mercedes  and  RIOS DE MOLINA, María del Carmen. Relación estructura-función de la enzima uroporfirinógeno descarboxilasa: implicancias para la comprensión y el tratamiento de la porfiria cutánea tarda. Acta bioquím. clín. latinoam. [online]. 2023, vol.57, n.1, pp.3-15. ISSN 0325-2957.

Human uroporphyrinogen decarboxylase (UROD-h) is the fifth enzyme in the heme biosynthetic pathway and its deficient activity, related to mutations in its gene, is associated with a subset of porphyrias. The objective of this work was to study the relationship between the dimerisation of the enzyme and its enzymatic activity and to verify if the dimerisation of UROD-h is essential both for the first stage of the reaction (urogen→heptagen), and for the second stage (heptagen→ coprogen). With this objective, the UROD-h was expressed and purified to homogeneity, the dimer- monomer behaviour was analysed under different conditions, which could shift the dimerisation equilibrium, and the enzymatic activity was evaluated under these conditions. The results obtained suggest that the active species for the first stage of the reaction is the homodimer, and both the dimer and the monomer behaved as active species for the second stage of the reaction. It is proposed that clinical mutations such as Y311C, existing in porphyria cutanea tarda patients, could affect dimer stability and could be the target of future gene therapies.

Keywords : Uroporphyrinogen decarboxylase; Dimerization equilibrium; Uroporphyrinogen; Pentaporphyrinogen; Enzymatic purification; Reaction mechanisms; Porphyria cutanea tarda; Mutations.

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