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)

Rat brain contains substantial concentrations of free malonate (192 nmol/g wet weight) but origin and biological importance of the dicarboxylic acid are poorly understood. A dietary source has been excluded. A recently described malonyl-CoA decarboxylase deficiency is associated with malonic aciduria and clinical manifestations, including mental retardation. In an effort to study the metabolic origin of free malonate, several labeled acetyl-CoA precursors were administered by intracerebral injection. [2-14C]pyruvate or [1,5-14C]citrate produced radioactive glutamate but failed to label malonate. In contrast, [1-14C]acetate, [2-14C]acetate, and [1-14C]butyrate were converted to labeled glutamate and malonate after the same route of administration. The intracerebral injection of [1-14C]-beta-alanine as a precursor of malonic semialdehyde and possibly free malonate did not give rise to radioactivity in the dicarboxylate. The labeling pattern of malonic acid is compatible with the reaction sequence: acetyl-CoA----malonyl-CoA----malonate. The final step is thought to occur by transfer of the CoA-group from malonyl-CoA to succinate and/or acetoacetate. Labeling of malonate from acetate is most effective at the age of 7 days when the net concentration of the dicarboxylic acid in rat brain is still very low. At this age, butyrate was a better precursor of malonate than acetate. It is proposed that fatty acid oxidation provides the acetyl-CoA which functions as the precursor of free brain malonate. Compartmentation of malonate biosynthesis is likely because the acetyl-CoA precursors citrate and pyruvate are ineffective.
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PMID:The origin of free brain malonate. 167 5

Calcium hopantenate (HOPA-Ca), which is obtained by substituting the beta-alanine of pantothenic acid for gamma-amino butyric acid (GABA), is a therapeutic drug for mental retardation and cerebrovascular dementia. HOPA-Ca is known to produce convulsive seizures in some patients although it is also true that this improves EEG abnormalities and suppresses epileptic seizures. Thus, clinical observations suggest that HOPA-Ca exerts a paradoxical influence on epilepsy. In order to gain further insight into the influence of HOPA-Ca on epilepsy, we examined its effects on the generalized seizure-triggering threshold (GST) of kindled amygdaloid (AM) seizure and on the rate of AM kindling in rats. Male Wistar rats weighing 200-250 g were used. Under pentobarbital anesthesia, a bipolar electrode, made of twisted stainless steel wire 0.2 mm in diameter, was stereotaxically implanted into the left AM. Daily electrical stimulation was given at the intensity of afterdischarge threshold (ADT). Electrical stimulation was continued until at least five consecutive generalized convulsions were evoked. Subsequently, the stimulus intensity was daily lowered by 20-microA steps and the last stimulus intensity for evoking generalized convulsion was designated as the GST. Experiment 1. Influence of HOPA-Ca on the GST; HOPA-Ca was dissolved in saline as a vehicle. Injections of 50, 100, 250, 500 mg/kg HOPA-Ca were given intraperitoneally 60 min before the stimulation at the GST. The GST never changed with vehicle injection. The GST increase was never observed with any amount of HOPA-Ca. However, the GST dropped flowing HOPA-Ca infection independent of its amount. The GST reduction was always 20-microA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Facilitatory effect of calcium hopantenate on amygdaloid kindling in rats]. 322 34

Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterised by thymine-uraciluria in homozygous deficient patients and has been associated with a variable clinical phenotype. In order to understand the genetic and phenotypic basis for DPD deficiency, we have reviewed 17 families presenting 22 patients with complete deficiency of DPD. In this group of patients, 7 different mutations have been identified, including 2 deletions [295-298delTCAT, 1897delC], 1 splice-site mutation [IVS14+1G>A)] and 4 missense mutations (85T>C, 703C>T, 2658G>A, 2983G>T). Analysis of the prevalence of the various mutations among DPD patients has shown that the G-->A point mutation in the invariant splice donor site is by far the most common (52%), whereas the other six mutations are less frequently observed. A large phenotypic variability has been observed, with convulsive disorders, motor retardation and mental retardation being the most abundant manifestations. A clear correlation between the genotype and phenotype has not been established. An altered beta-alanine, uracil and thymine homeostasis might underlie the various clinical abnormalities encountered in patients with DPD deficiency.
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PMID:Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. 1007 Nov 85