Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of lipoamide dehydrogenase was abnormally heat-labile in homogenized platelets from seven patients with as recessive ataxia conforming to the syndrome of Friedreich ataxia or clinical variants. Taken together, the abnormality and previous findings of low activity and abnormal kinetic properties are compatible with a change in the conformation of the enzyme in these patients.
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PMID:Lipoamide dehydrogenase: rapid heat inactivation in platelets of patients with recessively inherited ataxia. 689 19

Pyruvate and palmitate oxidations by cultured fibroblasts suspensions were measured in optimized conditions and proved to be within normal range in the cells from Friedreich's patients. However, when pyruvate oxidation was measured by direct assay of the pyruvate dehydrogenase complex, this enzyme activity proved to be significantly lower in Friedreich's than in controls' cells. These abnormalities were not observed when the cells were sonicated. Moreover, lipoamide dehydrogenase activity. Km and Vmax were within the normal range in Friedreich's cells. These data suggest that the low activities of the PDH complex are not a primary defect in Friedreich's ataxia, but are more likely related to membrane abnormalities in Friedreich's cells.
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PMID:Friedreich's ataxia in northern Italy. II. Biochemical studies in cultured cells. 689 62

Serum lipoamide dehydrogenase activity and kinetics were studied in nine patients with Friedreich's ataxia before and three months after therapy with oral lecithin. Results disclosed a significant reduction in LAD inhibition by NADH in all patients after therapy. Three patients normalized their increased Km for lipoamide and one patient showed the opposite results after therapy. Two patients ceased lecithin after one month. All seven patients who remained in the trial group and one additional patient, showed subjective and objective signs of improvement in physical resistance. This study has offered some biochemical basis for the apparent clinical improvement in patients with Friedreich's ataxia who undergo lecithin therapy.
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PMID:Correlation between serum lipoamide dehydrogenase activity and phosphatidylcholine therapy in Friedreich's ataxia. 689 63

Pyruvate and palmitate oxidations by cultured fibroblast suspensions were measured in optimized conditions and proved to be within normal range in the cells from Friedreich's patients. But when pyruvate oxidation was measured by direct assay of the pyruvate dehydrogenase complex, this enzyme activity proved to be significantly lower in Friedreich's than in controls' cells. These abnormalities were not observed when the cells were sonicated. Moreover, lipoamide dehydrogenase activity Km and Vmax were within the normal range in Friedreich's cells. These data suggest that the low activities of the PDH complex are not a primary defect in Friedreich's ataxia but are more likely to be related to membrane abnormalities in Friedreich's cells.
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PMID:Friedreich's ataxia II. Biochemical studies in cultured cells. 689 44

Enzyme activities of a alpha-ketoglutarate dehydrogenase complex (alpha KGDHC) and one of its constituent subunits, dihydrolipoamide dehydrogenase (E3), are reported to be reduced in non-CNS tissues of some patients with Friedreich's ataxia (FA); however, the results are highly conflicting. To determine whether an enzyme abnormality occurs in brain, we measured immunoreactive levels of the three alpha KGDHC subunits, namely, alpha-ketoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and E3 in postmortem frontal, occipital and cerebellar cortices of 18 control subjects, 9 patients with FA and, for comparison, 12 patients with spinocerebellar ataxia type 1 (SCA1). Decreased (-20 to -31%) levels of E3 were observed in all three examined areas of the patients with FA with the changes statistically significant in cerebellar and frontal cortices. The E3 reduction could be explained by a loss of alpha KGDHC or other dehydrogenase complexes (e.g. pyruvate dehydrogenase complex) which utilize this subunit. In SCA1, enzyme changes were limited to E2 in cerebellar (-26%) and frontal (-19%) cortices. Although the E3 and E2 reductions are only slight, and may represent secondary events, the changes in this key Krebs cycle enzyme could exacerbate degenerative processes in both of the spinocerebellar ataxia disorders.
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PMID:Immunoreactive levels of alpha-ketoglutarate dehydrogenase subunits in Friedreich's ataxia and spinocerebellar ataxia type 1. 873 79

Friedreich ataxia (FA) is a cardioneurodegenerative disease caused by deficient frataxin expression. This mitochondrial protein has been related to iron homeostasis, energy metabolism, and oxidative stress. Previously, we set up a cardiac cellular model of FA based on neonatal rat cardiac myocytes (NRVM) and lentivirus-mediated frataxin RNA interference. These frataxin-deficient NRVMs presented lipid droplet accumulation, mitochondrial swelling and signs of oxidative stress. Therefore, we decided to explore the presence of protein thiol modifications in this model. With this purpose, reduced glutathione (GSH) levels were measured and the presence of glutathionylated proteins was analyzed. We observed decreased GSH content and increased presence of glutahionylated actin in frataxin-deficient NRVMs. Moreover, the presence of oxidized cysteine residues was investigated using the thiol-reactive fluorescent probe iodoacetamide-Bodipy and 2D-gel electrophoresis. With this approach, we identified two proteins with altered redox status in frataxin-deficient NRVMs: electron transfer flavoprotein-ubiquinone oxidoreductase and dihydrolipoyl dehydrogenase (DLDH). As DLDH is involved in protein-bound lipoic acid redox cycling, we analyzed the redox state of this cofactor and we observed that lipoic acid from pyruvate dehydrogenase was more oxidized in frataxin-deficient cells. Also, by targeted proteomics, we observed a decreased content on the PDH A1 subunit from pyruvate dehydrogenase. Finally, we analyzed the consequences of supplementing frataxin-deficient NRVMs with the PDH cofactors thiamine and lipoic acid, the PDH activator dichloroacetate and the antioxidants N-acetyl cysteine and Tiron. Both dichloroacetate and Tiron were able to partially prevent lipid droplet accumulation in these cells. Overall, these results indicate that frataxin-deficient NRVMs present an altered thiol-redox state which could contribute to the cardiac pathology.
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PMID:Frataxin-deficient cardiomyocytes present an altered thiol-redox state which targets actin and pyruvate dehydrogenase. 3227 39


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