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Inhibition of β‐ureidopropionase by propionate may contribute to the neurological complications in patients with propionic acidaemia
Author(s) -
Gennip A. H.,
Lenthe H.,
Abeling N. G. G. M.,
Scholten E. G.,
Kuilenburg A. B. P.
Publication year - 1997
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1005338230321
Subject(s) - medicine , pediatrics , medical school , chemistry , medical education
Propionic acidaemia is due to a primary deficiency of propionyl-CoA carboxylase (EC 6.4.1.3) activity. The clinical picture is characterized by repeated relapses and neurological sequelae are common. Among the neurological complications, focal and general seizures as well as EEG abnormalities are often observed. During relapse substantial accumulation of propionate occurs in all body fluids. β-Ureidopropionase (UP, EC 3.5.1.6) is the third enzyme in the degradation pathway of uracil and thymine. It catalyses the degradation of both β-ureidopropionic acid and β-ureidoisobutyric acid to β-alanine and β-aminoisobutyric acid, respectively. A deficiency of UP or one of the other enzymes of pyrimidine degradation leads to a diminished production of β-alanine, a neurotransmitter amino acid. Diminished production of β-alanine also occurs in other pyrimidine degradation defects and is presumed to be a contributing factor in the neurological abnormalities seen in the patients with those defects (Van Gennip et al 1997). Propionate has been reported to inhibit UP in Euglena gracilis (Wasternack et al 1979). We wondered whether inhibition of UP by propionate or β-hydroxypropionate could be demonstrated in vitro in human liver and in vivo in patients with propionic acidaemia.