Oxidative stress in patients with phenylketonuria.
Phenylketonuria (PKU) is an autossomal recessive disease caused by phenylalanine-4-hydroxylase deficiency, which is a liver-specific enzyme that catalyzes the hydroxylation of l-phenylalanine (Phe) to l-tyrosine (Tyr). The deficiency of this enzyme leads to the accumulation of Phe in the tissues and plasma of patients. The clinical characterization of this disease is mental retardation and other neurological features. The mechanisms of brain damage are poorly understood. Oxidative stress is observed in some inborn errors of intermediary metabolism owing to the accumulation of toxic metabolites leading to excessive free radical production and may be a result of restricted diets on the antioxidant status. In the present study we evaluated various oxidative stress parameters, namely thiobarbituric acid-reactive species (TBA-RS) and total antioxidant reactivity (TAR) in the plasma of PKU patients. The activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were also measured in erythrocytes from these patients. It was observed that phenylketonuric patients present a significant increase of plasma TBA-RS measurement, indicating a stimulation of lipoperoxidation, as well as a decrease of plasma TAR, reflecting a deficient capacity to rapidly handle an increase of reactive species. The results also showed a decrease of erythrocyte GSH-Px activity. Therefore, it is presumed that oxidative stress is involved in the pathophysiology of the tissue damage found in PKU.
Sirtori
L R
LR
Medical Genetics Service, HCPA, Rua Ramiro Barcelos, 2350 CEP 90.035-003, Porto Alegre, RS, Brazil.
Dutra-Filho
C S
CS
Fitarelli
D
D
Sitta
A
A
Haeser
A
A
Barschak
A G
AG
Wajner
M
M
Coelho
D M
DM
Llesuy
S
S
Belló-Klein
A
A
Giugliani
R
R
Deon
M
M
Vargas
C R
CR
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004798:Enzymes / Q000097:blood; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000209:etiology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D004798:Enzymes; D017392:Thiobarbituric Acid Reactive Substances; D010649:Phenylalanine