Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.3.5.1 (
succinate dehydrogenase
)
8,177
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Phenylketonuria (PKU) is biochemically characterized by the accumulation of phenylalanine (Phe) and its metabolites in tissues of affected children. Neurological damage is the clinical hallmark of PKU, and Phe is considered the main neurotoxic metabolite in this disorder. However, the mechanisms of neurotoxicity are poorly known. The main objective of the present work was to measure the activities of the mitochondrial respiratory chain complexes (RCC) and
succinate dehydrogenase
(
SDH
) in brain cortex of Wistar rats subjected to chemically induced
hyperphenylalaninemia
(
HPA
). We also investigated the in vitro effect of Phe on
SDH
and RCC activities in the cerebral cortex of 22-day-old rats.
HPA
was induced by subcutaneous administration of 2.4 micromol/g body weight alpha-methylphenylalanine, a phenylalanine hydroxylase inhibitor, once a day, plus 5.2 microM/g body weight phenylalanine, twice a day, from the 6th-21st postnatal day. The results showed a reduction of
SDH
and complex I + III activity in brain cortex of rats subjected to
HPA
. We also verified that Phe inhibited the in vitro activity of complexes I + III, possibly by competition with NADH. Considering the importance of
SDH
and RCC for the maintenance of energy supply to brain, our results suggest that energy deficit may contribute to the Phe neurotoxicity in PKU.
...
PMID:Inhibition of the mitochondrial respiratory chain by phenylalanine in rat cerebral cortex. 1206 49
