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Query: UMLS:C0268596 (EMA)
 2,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied metabolic, polypeptide and genetic variation in eight glutaric acidemia type II (GA II) patients with electron transfer flavoprotein (ETF) deficiency. As measured by 3H-fatty acid oxidations in fibroblasts, beta-oxidation pathway flux correlated well with clinical phenotypes. In six patients with severe neonatal onset GA II, oxidation of [9,10(n)-3H]-palmitate ranged from 2% to 22% of control and of [9,10(n)-3H]myristate, from 2% to 26% of control. Of two patients with late onset GA II, one had intermediate residual activities with these substrates and the other normal activities. Radiolabeling and immunoprecipitation studies revealed that three of the six neonatal onset GA II patients had greatly diminished or absent alpha- and beta-ETF subunits, consistent with a failure to assemble a stable heterodimer. Another neonatal onset patient showed normal synthesis of beta-ETF but decreased synthesis of alpha-ETF. Two neonatal onset and two late onset GA II patients showed normal synthesis of both subunits. Analysis of the pre-alpha-ETF coding sequence revealed seven different mutations in the six patients with neonatal onset GA II. The most common mutation was a methionine for threonine substitution at codon 266 found in four unrelated patients, while all the other mutations were seen in single patients. No mutations were detected in the two patients with late onset GA II.
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PMID:Glutaric acidemia type II. Heterogeneity in beta-oxidation flux, polypeptide synthesis, and complementary DNA mutations in the alpha subunit of electron transfer flavoprotein in eight patients. 143 Jan 99

Glucoamylase II (GA II) immobilized to Eupergit C and CIZ as a porous and nonporous matrix shows enzymatic characteristics indistinguishable from those of the free enzyme, except for reduced specific activity. Since this decrease is equally observed for both matrices, it has to be ascribed to nonproductive fixation of the enzyme or steric hindrance rather that perturbations caused by "inner diffusion" effects. Authenticity refers to the optimum pH for catalytic activity, Michaelis constants for starch and maltoheptaose, as well as identical stability toward temperature, pH, and guanidinium chloride (GdmCl). On the basis of these data, the two-state mechanism observed for the equilibrium transitions of the free enzyme may be assumed to hold also for the immobilized enzyme. Renaturation after preceding denaturation in 6.4 and 7 M GdmCl leads to widely differing yields depending on the conditions. Shifting the denaturant concentration stepwise back to nondenaturing GdmCl concentrations leads to a broad range of "hysteresis" accompanied by aggregation. Rapid dilution of the free and immobilized enzymes at pH greater than 6 and sufficiently low protein concentration leads to reactivation yields of 80 and 45%, respectively. For the free enzyme, reconstitution at lower pH is determined by the kinetic competition of folding and aggregation. In the case of the immobilized enzyme, "entangling" of the matrix with the unfolded polypeptide chain competes with renaturation.
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PMID:Authenticity and reconstitution of immobilized enzymes: characterization and denaturation/renaturation of glucoamylase II. 177 17

Newly identified forms of electron transfer flavoprotein (ETF) deficiency in two patients with glutaric aciduria type II (GA II) were described. GA II has been attributed to a defect of either ETF or ETF dehydrogenase, resulting in multiple acyl-CoA dehydrogenation deficiency. ETF is a mitochondrial flavoprotein consisting of an alpha-subunit, alpha-ETF, and a beta-subunit, beta-ETF. We used pulse-chase experiments to examine the biosynthesis of ETF in fibroblasts from two patients with GA II. Patient 1 was a boy with the neonatal onset form, but without congenital anomalies, who is living at age 2 y. A defect of beta-ETF biosynthesis was noted in this patient. Patient 2 was a boy with the neonatal onset form with congenital anomalies who died on the 3rd postnatal day. He presented with a peculiar face and polycystic kidneys. In patient 2, both alpha- and beta-ETF were synthesized, but both the subunits were rapidly degraded. The lability of ETF was considered to be the cause of GA II in this patient. These two cases appear to be new forms of ETF deficiency in GA II.
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PMID:Newly identified forms of electron transfer flavoprotein deficiency in two patients with glutaric aciduria type II. 200 Feb 60

A conjugate of an anti-gastric cancer monoclonal antibody and mitomycin C linked by polyaldehyde dextran T-40 (MGb2-PAD-MMC) was prepared. Nude mice inoculated with human gastric cancer (SGC-7901) xenograft in bilateral subrenal capsule were treated ip with the conjugate at a daily dose containing MGb2 22.4 mg/kg and MMC 1 mg/kg for 6 d since 4 h after inoculation. The efficacy of the conjugate was estimated by the reduction of tumor size which calculated by T/C (%) was 32.2%. If MGb2 in the conjugate was replaced by a normal nude mice IgG (NIgG-PAD-MMC) or the nude mice were treated ip with the dose of MMC alone, the tumor T/C (%) were 58 and 87%, respectively. It was statistically significant between MGb2-PAD-MMC and NIgG-PAD-MMC or MMC treatment. When the above mentioned nude mice with SGC-7901 were treated ip with thrice dose of the conjugate (MGb2 67.2 mg/kg and MMC 3 mg/kg) for 6 d, the tumor growth was inhibited completely. Nevertheless, the same dose of MMC was given to the nude mice resulted in toxic appearance included anorexia, weight loss or even death. Furthermore, when the nude mice were treated ip with MGb2-PAD-MMC 24 h after inoculation, no apparent therapeutic effect was seen. In some experiments, nude mice inoculated with another human transplanted gastric tumor (GA II) xenograft treated ip with a conjugate of MGb2 and MMC or daunorubcin (Dau) 1 day after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of immuno-drug conjugates on growth of human gastric cancer xenograft in subrenal capsule of nude mice]. 213 Jun 22

Glutaric acidemia type II (GA II) is a human genetic disorder. It has been suggested that the primary defect in this disorder is a deficiency of a protein involved in electron transport between the acyl-CoA dehydrogenases and the bc1 complex of the mitochondrial respiratory chain. Antisera were raised to purified porcine electron transfer flavoprotein (ETF) and electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO). The antisera were used to detect the two electron transferases in control and GA II fibroblasts by immunoblotting. Fibroblasts from three unrelated GA II patients were deficient in immunologically detectable ETF:QO and extracts from these three fibroblast lines contained no detectable ETF:QO catalytic activity. Fibroblasts from parents of two of these patients had ETF:QO activity intermediate between activities in control fibroblasts and fibroblasts from the patients. These data indicate that the primary defect in these patients is a deficiency of ETF:QO and that the mode of transmission of the gene is autosomal recessive. Fibroblasts from two other patients with severe GA II had normal levels of ETF-QO activity and antigen but were deficient in immunoreactive ETF. These findings show that GA II results from a deficiency of ETF in some patients and ETF:QO in others. In addition, these investigations provide strong evidence for the specificity and physiological function of the iron-sulfur flavoprotein ETF:QO.
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PMID:Deficiency of electron transfer flavoprotein or electron transfer flavoprotein:ubiquinone oxidoreductase in glutaric acidemia type II fibroblasts. 298 28

Glutaric acidemia type II (GA II) is a metabolic disorder caused by deficiency of electron transport flavoprotein or its oxyreductase. It is characterized by acidosis, hypoglycemia, hyperammonemia, organic aciduria, and "sweat-sock" odor. Neonatal GA II differs from most inborn metabolic errors in that there are prominent congenital malformations. We recently observed two infants at autopsy with GA II whose malformations included: subcortical renal glomerular cysts, renal medullary dysplasia, cerebral pachygyria, pulmonary hypoplasia, and facial dysmorphism. In addition, there was lipid accumulation in liver, heart, and renal tubular epithelium, tissues that use fatty acids as a primary source of energy. Review of previous reports of 12 patients showed that these lesions are typical of neonatal GA II. The pattern of lesions, in particular the striking localization of renal dysplasia to the medulla, suggests that the malformations may be the consequence of an accumulation of toxic metabolites that is not corrected by placental transfer.
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PMID:Glutaric acidemia type II. Comparison of pathologic features in two infants. 317 28

Glutaric aciduria type II (GA II) was proved in a neonate who presented shortly after birth with respiratory distress, metabolic acidosis, non-ketotic hypoglycaemia and a sweaty-feet-like odour. The diagnosis was based on elevated levels of glutaric and other acids in the urine and on studies on cultured skin fibroblasts where defective metabolism of fatty acids of varying chain length was demonstrated. Antenatal diagnosis was performed on a subsequent pregnancy in this family where an abnormal amniotic fluid organic acid profile together with defective fatty acid oxidation in cultured amnion cells was indicative of GA II in the fetus. This is the first report of this genetic disorder in a South African family and it should be considered in suspected organic acidaemia in the neonatal period.
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PMID:Postnatal and antenatal laboratory diagnosis of glutaric aciduria II in a South African family. 357 10

A boy, now 22 months old, is described who presented at the age of 6 weeks with hypoglycaemic coma. The excretion pattern of organic acids in the urine was consistent with glutaric aciduria type II (GA II). A high energy diet low in fat and protein was given. Treatment with riboflavine resulted in an improvement of the metabolite profile, and the patient gained weight. However, a tendency to hypoglycaemia and severe hypotonia persisted. Due to muscle weakness, aggravated by infections, artificial ventilation was necessary during three periods. Serum carnitine level was low. Treatment with carnitine, started during the third period of artificial ventilation, led to some improvement of muscle strength, but he still could not breathe without support. Treatment with insulin, combined with further enrichment of the diet with glucose, resulted in an increase in muscular strength and in weight gain. Thirteen families with GA II have been described upto now. This is the first patient with a severe form of the disorder wo has survived the 1st year of life. Treatment and metabolic studies are presented.
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PMID:Glutaric aciduria type II: treatment with riboflavine, carnitine and insulin. 639 38

Using cultured skin fibroblasts, we studied the heterogeneity of inborn errors of leucine metabolism such as isovaleric acidemia (IVA), glutaric aciduria type II (GA II), and multiple carboxylase deficiency (MC). We first developed a simple macromolecular-labeling test to measure the ability of cells to oxidize [1-14C]isovaleric acid in situ in culture. Cells from two different lines were fused using polyethylene glycol, and the ability of the heterokaryons to oxidize [1-14C]isovaleric acid was tested by the macromolecular-labeling test. The MC line complemented with all 10 IVA lines tested; heterokaryons showed 99 +/- 68% more activity than the unfused mixture of component cells. GA II/IVA heterokaryons exhibited poor growth, but when the culture remained confluent, the GA II cells complemented with all six IVA lines tested, showing a 71 +/- 41% increase in activity. The relatively large standard deviations are due to a few experiments in which significant enhancement of macromolecular-labeling test activity was not observed upon fusion, but significant complementation was clearly observed in repeats of the same combinations. These results are consistent with our previous findings, which indicated that the decreased ability of GA II cells to oxidize isovaleryl-CoA involves a defective electron-transporting system rather than a defective isovaleryl-CoA dehydrogenase. IVA/IVA heterokaryons showed no complementation in any combination tested, indicating no detectable heterogeneity in isovaleric acidemia. This finding indicates that the same gene is mutated in all IVA lines. Previous results indicated that this gene codes for isovaleryl-CoA dehydrogenase.
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PMID:Complementation studies of isovaleric acidemia and glutaric aciduria type II using cultured skin fibroblasts. 663 May 17

The previous biochemical evidence had suggested that glutaric aciduria type II (GA II) is due to deficient dehydrogenation of multiple short-chain acyl coenzyme A's (CoA's), bu the precise biochemical mechanism underlying this disease was unknown. We investigated substrate oxidation and in vitro activities of isovaleryl CoA- and butyryl CoA dehydrogenases as well as that of electron-transferring flavoprotein (ETF) in cultured skin fibroblasts from a patient with GA II. GA II cells have a markedly decreased ability to oxidize [1-14C]butyrate, [2-14C]lysine, and [2,14C]leucine (3, 9, and 9% of control values, respectively). Mitochondrial isovaleryl CoA- and butyryl CoA dehydrogenase activities in GA II cells were determined using a tritium release assay with [2,3-3H] acyl-CoA's as substrate. When an artificial electron acceptor, phenazine methosulfate (PMS) was not added in the assay media, these activities were 108 and 113% of controls, respectively. This represents the normal abilities of the dehydrogenases in GA II cells to bind the substrate and to catalyze tritium exchange between the bound substrate and solvent. When PMS was added to the assay mixture, these activities were 88 and 70% of control values, respectively, indicating that these enzymes can both dehydrogenate their substrates normally and then transfer electrons to an acceptor (PMS). ETF activity in mitochondrial sonic supernatants from GA II cells, as assessed by a newly devised method, was 159% of control values. These observations suggest that the acyl CoA dehydrogenases themselves and ETF are not defective in GA II. Therefore, the deficiency of another common gene product necessary for the function of all the affected acyl CoA dehydrogenases must be sought to explain the etiology of GA II.
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PMID:Glutaric aciduria type II: in vitro studies on substrate oxidation, acyl-CoA dehydrogenases, and electron-transferring flavoprotein in cultured skin fibroblasts. 720 50


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