ALAD Inhibition by Porphobilinogen Rationalizes the Accumulation of δ-Aminolevulinate in Acute Porphyrias.

ABSTRACT: Patients with major forms of acute hepatic porphyria present acute neurological attacks with overproduction of porphobilinogen (PBG) and δ-aminolevulinic acid (ALA). Even if ALA is considered the most likely agent inducing the acute symptoms, the mechanism of its accumulation has not been experimentally demonstrated. In the most frequent form, acute intermittent porphyria (AIP), inherited gene mutations induce a deficiency in PBG deaminase; thus, accumulation of the substrate PBG is biochemically obligated but not that of ALA. A similar scenario is observed in other forms of acute hepatic porphyria (i.e., porphyria variegate, VP) in which PBG deaminase is inhibited by metabolic intermediates. Here, we have investigated the molecular basis of δ-aminolevulinate accumulation using in vitro

SUBMITTER: San Juan I 

PROVIDER: S-EPMC9631992 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature