Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical and laboratory features of a 3-mo-old black male infant with glutathione (GSH) synthetase deficiency of the generalized type was evaluated. Partial albinism, brisk hemolytic anemia, recurrent febrile episodes, and mental retardation were noted. Also, severe recurrent metabolic acidosis and marked oxoprolinemia and oxoprolinuria were found in the proband but not in his first-degree relatives. The relationship of these disease manifestations to the underlying metabolic defect is discussed.
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PMID:Hemolytic anemia, recurrent metabolic acidosis, and incomplete albinism associated with glutathione synthetase deficiency. 688 23

The adverse effects of the maternal consumption of alcohol on the fetus have been recognized for centuries. Fetal alcohol syndrome is characterized by pre- and postnatal growth retardation, mental retardation, behavioral deficits, and facial deformities. Despite numerous animal studies, the biochemical mechanism(s) by which alcohol produces teratogenic effects on the developing fetus are not well understood. Several studies have shown that administration of alcohol to adult rats produces a decrease in hepatic levels of glutathione (GSH). In utero administration of alcohol has also been shown to produce a decrease in GSH levels, as well as prenatal growth retardation and intrauterine death. In an effort to determine if GSH may have a vital role in protecting the fetus against the teratogenic effects of alcohol, buthionine (SR)-sulfoximine (BSO) was used to deplete GSH levels in the mother and fetus. Timed pregnant Sprague-Dawley rats were placed on a liquid BioServ diet containing either 0%, 11%, 23%, 29%, 31%, 33%, or 35% ethanol-derived calories, with or without BSO (888 mg/kg/24 hr), starting on day 1 of pregnancy. Another set of mothers were fed lab chow and water as a control group for the liquid diet. The mothers were maintained on the diet until gestation day 21 when they were anesthetized with sodium pentobarbital and the pups delivered by cesarean section. The offspring were counted, weighed, killed, and the brain and liver weighed. The effects of BSO on the alcohol dose-response curves (body weights, brain weights, and litter number) were then determined to ascertain if a depletion in GSH potentiated the effects of alcohol. In utero administration of BSO, aside from the depletion of GSH in the liver and brain in the developing fetus, produced a shift to the left in the alcohol dose-response curve.
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PMID:Effects of buthionine sulfoximine on the outcome of the in utero administration of alcohol on fetal development. 890 78

Down syndrome is the most common cause of mental retardation, affecting 1 in 700-800 liveborn infants. Although numerous biochemical abnormalities accompanying the syndrome have not yet been completely clarified, the antioxidant defense system enzymes have shown to be altered due to increased gene dosage on chromosome 21 and overproduction of superoxide dismutase (SOD-1 or Cu/Zn SOD). The purpose of this study was to investigate the activities of SOD-1 and glutathione peroxidase (GSH-Px) enzymes and the levels of their cofactors zinc (Zn), copper (Cu) and selenium (Se) in plasma of 20 Down syndrome patients. In comparison with age and sex-matched controls (n = 15), plasma GSH-Px, SOD, and Cu levels were significantly decreased in the patient group, but Zn and Se concentrations remained unchanged.
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PMID:Antioxidative metabolism in Down syndrome. 982 38

Tissue accumulation of L-phenylalanine (Phe) is the biochemical hallmark of human phenylketonuria (PKU), an inherited metabolic disorder clinically characterized by mental retardation and other neurological features. The mechanisms of brain damage observed in this disorder are poorly understood. In the present study we investigated some oxidative stress parameters in the brain of rats with experimental hyperphenylalaninemia. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were measured in the brain of the animals. We observed that chemiluminescence is increased and TRAP is reduced in the brain of hyperphenylalaninemic rats. Similar data were obtained in the in vitro experiments using Phe at various concentrations. CAT activity was significantly inhibited by Phe in vitro and in vivo, whereas GSH-Px activity was reduced in vivo but not in vitro and SOD activity was not altered by any treatment. The results indicate that oxidative stress may be involved in the neuropathology of PKU. However, further studies are necessary to confirm and extend our findings to the human condition and also to determine whether an antioxidant therapy may be of benefit to these patients.
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PMID:Experimental hyperphenylalaninemia provokes oxidative stress in rat brain. 1199 85

Hyperprolinemia type II is an autosomal recessive disorder caused by the severe deficiency of delta(1)-pyrroline-5-carboxylate dehydrogenase activity leading to tissue accumulation of proline (Pro). Most patients detected so far show neurological manifestations including epilepsy and mental retardation, whose pathophysiology is not yet fully established. In the present study, we determined the in vivo and in vitro effects of Pro on some parameters of oxidative stress, namely chemiluminescence, total radical-trapping antioxidant potential (TRAP) and the activity of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) from cerebral cortex of 29-day-old Wistar rats. Results showed that acute administration of Pro provoked a significant increase of chemiluminescence and a decrease of TRAP, whereas chronic administration of the metabolite did not alter these parameters. Furthermore, in vitro brain exposure to Pro resulted in increased chemiluminescence and decreased TRAP at Pro concentrations similar to those observed in tissues of hyperprolinemic patients (0.5-1.0 mM). As regards to the antioxidant enzymes, acute injection of Pro significantly decreased CAT activity and did not alter SOD and GSH-Px activities, whereas chronic Pro administration provoked a significant increase of CAT activity, a decrease of GSH-Px activity and did not modify SOD activity. Furthermore, CAT, GSH-Px and SOD activities were not affected by the presence of Pro in the incubation medium. The data indicate that Pro induces oxidative stress in vivo and in vitro, which may be involved in the brain dysfunction observed in hyperprolinemic patients.
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PMID:In vivo and in vitro effects of proline on some parameters of oxidative stress in rat brain. 1457 90

Histidinemia is an inherited metabolic disorder caused by deficiency of histidase activity, which leads to tissue accumulation of histidine and its derivatives. Affected patients usually present with speech delay and mental retardation, although asymptomatic patients have been reported. Considering that the pathophysiology of the neurological dysfunction of histidinemia is not yet understood and since histidine has been considered a pro-oxidant agent, in the present study we investigated the effect of histidine and one of its derivatives, l-beta-imidazolelactic acid, at concentrations ranging from 0.1 to 10 mM, on various parameters of oxidative stress in cerebral cortex of 30-day-old Wistar rats. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), thiobarbituric acid reactive substances (TBA-RS), and the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured in tissue homogenates in the presence of l-histidine or l-beta-imidazolelactic acid. We observed that l-histidine provoked an increase of chemiluminescence and a reduction of TRAP at concentrations of 2.5 mM and higher, while TBA-RS measurement, GSH-Px, CAT and SOD activities were not affected. Furthermore, l-beta-imidazolelactic acid provoked antioxidant effects at high concentrations (5-10 mM) as observed by the reduction of chemiluminescence, although this compound enhanced chemiluminescence at low concentrations (0.5-1 mM). These results suggest that in vitro oxidative stress is elicited by histidine but only at supraphysiological concentrations.
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PMID:Effects of histidine and imidazolelactic acid on various parameters of the oxidative stress in cerebral cortex of young rats. 1503 81

Guanidinoacetate methyltransferase deficiency (GAMT-deficiency) is an inherited neurometabolic disorder clinically characterized by epilepsy and mental retardation and biochemically by accumulation of guanidinoacetate (GAA) and depletion of creatine. Although the neurological symptoms are predominant, the pathogenesis of the brain dysfunction in this disorder is not yet established. In the present study we investigated the in vitro effect of GAA on Na+, K+-ATPase and Mg2+-ATPase activities in synaptic plasma membrane from hippocampus of young rats. Results showed that GAA significantly inhibited Na+, K+-ATPase activity without affecting Mg2+-ATPase activity. We also evaluated the effect of glutathione (GSH), trolox, Nomega-nitro-L-arginine methyl ester (L-NAME) and taurine (Tau) on the inhibition elicited by GAA on Na+, K+-ATPase activity. GSH, trolox, L-NAME and Tau per se did not alter Na+, K+-ATPase activity. However, L-NAME and taurine prevented the inhibitory effect of GAA on this enzyme activity. Our findings suggest that the inhibition of Na+, K+-ATPase activity caused by GAA is possibly mediated by nitric oxide (NO) formation and/or synaptic membrane alteration. The present data may contribute to the understanding of the neurological dysfunction characteristic of GAMT-deficient patients.
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PMID:Evaluation of the mechanism underlying the inhibitory effect of guanidinoacetate on brain Na+, K+-ATPase activity. 1524 54

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.
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PMID:Oxidative stress in patients with phenylketonuria. 1587 43

Prolidase is a Mn(2+)-dependent dipeptidase that cleaves imidodipeptides containing C-terminal proline or hydroxyproline. In humans, a lack of prolidase activity causes prolidase deficiency, a rare autosomal recessive disease, characterized by a wide range of clinical outcomes, including severe skin lesions, mental retardation, and infections of the respiratory tract. In this study, recombinant prolidase was produced as a fusion protein with an N-terminal histidine tag in eukaryotic and prokaryotic hosts and purified in a single step using immobilized metal affinity chromatography. The enzyme was characterized in terms of activity against different substrates, in the presence of various bivalent ions, in the presence of the strong inhibitor Cbz-Pro, and at different temperatures and pHs. The recombinant enzyme with and without a tag showed properties mainly indistinguishable from those of the native prolidase from fibroblast lysate. The protein yield was higher from the prokaryotic source, and a detailed long-term stability study of this enzyme at 37 degrees C was therefore undertaken. For this analysis, an 'on-column' digestion of the N-terminal His tag by Factor Xa was performed. A positive effect of Mn(2+) and GSH in the incubation mixture and high stability of the untagged enzyme are reported. Poly(ethylene glycol) and glycerol had a stabilizing effect, the latter being the more effective. In addition, no significant degradation was detected after up to 6 days of incubation with cellular lysate. Generation of the prolidase in Escherichia coli, because of its high yield, stability, and similarity to native prolidase, appears to be the best approach for future structural studies and enzyme replacement therapy.
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PMID:Human recombinant prolidase from eukaryotic and prokaryotic sources. Expression, purification, characterization and long-term stability studies. 1708 Nov 96

Histidinemia is an inherited metabolic disorder biochemically characterized by high concentrations of histidine in biological fluids. Usually affected patients are asymptomatic although some individuals have mental retardation and speech disorders. Considering the high prevalence of histidinemia and the scarce information on the effects of maternal histidinemia on their progeny, we investigated various parameters of oxidative stress in brain cortex and hippocampus of the offspring from female rats that received histidine (0.5 mg/g of body weight) in the course of pregnancy and lactation. At 21 days of age we found a significant increase of thiobarbituric acid reactive substances (TBARS), 2',7'-dihydrodichlorofluorescein oxidation, superoxide dismutase (SOD) activity, catalase (CAT) activity, total sulfhydryls and glutathione (GSH) content in cerebral cortex and hippocampus. We also verified that at 60 days of age, GSH, SOD and total sulfhydryls returned to normal levels in brain cortex, while the other parameters decreased in the same structure. In the hippocampus, at 60 days of age GSH returned to normal levels, CAT persisted elevated and the other parameters decreased. These results indicate that histidine administration to female rats can induce oxidative stress in the brain from the offspring, which partially recovers 40 days after breastfeeding stopped.
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PMID:Administration of histidine to female rats induces changes in oxidative status in cortex and hippocampus of the offspring. 2223 70


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