Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of rats with the vitamin B12 analogue hydroxy-cobalamin[c-lactam] (HCCL) impairs methylmalonyl-CoA mutase function and leads to methylmalonic aciduria due to intracellular accumulation of propionyl and methylmalonyl-CoA. Since accumulation of these acyl-CoAs disrupts normal cellular regulation, the present investigation characterized metabolism in hepatocytes and liver mitochondria from rats treated subcutaneously with HCCL or saline (control) by osmotic minipump. Consistent with decreased methylmalonyl-CoA mutase activity, 14CO2 production from 1-14C-propionate (1 mM) was decreased by 76% and 82% after 2-3 wk and 5-6 wk of HCCL treatment, respectively. In contrast, after 5-6 wk of HCCL treatment, 14CO2 production from 1-14C-pyruvate (10 mM) and 1-14C-palmitate (0.8 mM) were increased by 45% and 49%, respectively. In isolated liver mitochondria, state 3 oxidation rates were unchanged or decreased, and activities of the mitochondrial enzymes, citrate synthetase, succinate dehydrogenase, carnitine palmitoyltransferase, and glutamate dehydrogenase (expressed per milligram mitochondrial protein) were unaffected by HCCL treatment. In contrast, activities of the same enzymes were significantly increased in both liver homogenate (expressed per gram liver) and isolated hepatocytes (expressed per 10(6) cells) from HCCL-treated rats. The mitochondrial protein per gram liver, calculated on the basis of the recovery of the mitochondrial enzymes, increased by 39% in 5-6 wk HCCL-treated rats. Activities of lactate dehydrogenase, catalase, cyanide-insensitive palmitoyl-CoA oxidation, and arylsulfatase A in liver were not affected by HCCL treatment. Hepatic levels of mitochondrial mRNAs were elevated up to 10-fold in HCCL-treated animals as assessed by Northern blot analysis. Thus, HCCL treatment is associated with enhanced mitochondrial oxidative capacity and an increased mitochondrial protein content per gram liver. Increased mitochondrial oxidative capacity may be a compensatory mechanism in response to the metabolic insult induced by HCCL administration.
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PMID:Increased hepatic mitochondrial capacity in rats with hydroxy-cobalamin[c-lactam]-induced methylmalonic aciduria. 170 51

Practical and scientific aspects of prenatal detection of genetic disorders is discussed. The indications for intrauterine detection of familial biochemical and particular chromosomal disorders require assessment of the risks of transabdominal amniocentesis and of the reliability of diagnosis. A high degree of experience in cultivating amniotic fluid cells and in performing diagnostic tests is required. The obstetrician performing the amniocentesis should be responsible for referring the family to a physician who will perform the abortion. A high-risk group for which amniocentesis may be especially important includes families in which 1 parent is a carrier of a chromosomal rearrangement and in which the woman is a known carrier of an X-linked recessive disorder so that sex determination is important. A moderate-risk group includes women who become pregnant after age 40 in which the risk of having a child with a chromosomal aberration is greater than 1%. A low-risk group includes women over 35 and women who have previously borne a child with trisomic Down's syndrome. The experience gained in over 300 patients suggests that transabdominal aminocentesis carries minimal risks to mother and fetus. Analyses of amniotic fluid obtained by amniocentesis have resulted in antenatal diagnoses of Pompe's disease (deficient alpha-1, 4-glucosidase), Tay-Sachs disease (deficient hexosaminidase A), mucopolysaccharidosis (quantitative and qualitative changes in mucopolysaccharides), methylmalonic aciduria (increased methylamlonate), and adrenogenital syndrome (increase 17-ketosteroids and pregnanetriol). There is a lack of consensus on the reliability of several of these diagnoses resulting from the direct analysis of amniotic fluid. Analyses of uncultured amniotic fluid cells have resulted in diagnoses of Pompe's disease (ultrastructural changes) and Tay-Sachs disease. Analyses of cultivated amniotic fluid cells have enabled diagnoses of galactosemia (deficient galactose-1-phosphate uridyl transferase), X-linked uric aciduria (by autoradiography), lysosomal acid phosphatase deficiency, metachromatic leukodystrophy (deficientaryl sulfatase A), mucopolysaccharidosis, cystic fibrosis (metachromatic granules), and Marfan's syndrome (metachromatic granules). Methylmalonic aciduria has been detected in utero by marternal methymalonate excretion. Adrenogenital syndrome has been detected by urinary estriol.
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PMID:Present status of amniocentesis in intrauterine diagnosis of genetic defects. 511 31