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 mean percentage of linoleate to total fatty acids in phosphatidylcholine and lysophosphatidylcholine fractions of serum phospholipids from neuropathic patients with HMN (hereditary motor neuropathy, also called distal type of progressive muscular atrophy), HMSN-I and HMSN-II (two types of peroneal muscular atrophy), and FA (Friedreich's ataxia) was reduced by approximately 10--20% (P less than 0.001). On the other hand, the mean percentage of nervonic acid in sphingomyelin was elevated by 9--20%. No significant difference was observed in phosphatidylethanolamine between neuropathic patients and control subjects. The mean concentration of phosphatidylcholine and sphingomyelin was also significantly reduced in neuropathic patients (except in HMN and HMSN-III). A significant correlation between endogenous 2-linoleoyl-sn-glycerol-3-phosphocholine and cholesteryl linoleate synthesis in vitro suggests that the decreased activity of phosphatidylcholine acyltransferase (EC 2.3.1.43; LCAT) in neuropathic patients is influenced by the fatty acid composition of their lipoprotein substrate. Furthermore, the reduction of phosphatidylcholine and of cholesteryl linoleate synthesis in vitro in neuropathic patients was affected by age and sex. It is unlikely that the reduced linoleate level in serum phosphatidylcholine for most, possibly all, of the inherited neuropathies studied here reflects a specific biochemical disorder. Possibly it reflects a more generalized biochemical alteration common to inherited neuropathy. One possibility is that biosynthesis of new membrane in axonal regeneration, segmental remyelination and Schwann cell hyperplasia may reduce the serum linoleate pool.
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PMID:Lipid abnormalities in hereditary neuropathy. Part 2. Serum phospholipids. 65 Feb 57

Friedreich's ataxia is caused by a deficit in frataxin, a small mitochondrial protein of unknown function that has been conserved during evolution. Previous studies have pointed out a role for frataxin in mitochondrial iron-sulfur (Fe-S) metabolism. Here, we have analyzed the incorporation of Fe-S clusters into yeast ferredoxin imported into isolated energized mitochondria from cells grown in the presence of glycerol, an obligatory respiratory carbon source. Similar amounts of apo-ferredoxin precursor were imported into mitochondria and processed in wild-type and yfh1-deleted (delta YF111) strains. However, the incorporation of Fe-S clusters into apo-ferredoxin was significantly reduced in delta YFH1 mitochondria. The newly assembled ferredoxin was stable, excluding the possibility that the decreased incorporation was a result of increased oxidative damage. When delta YFH1 cells were grown in raffinose medium, the formation of holo-ferredoxin was low, as a consequence of the decrease in ferredoxin precursor import into mitochondria. However, the decrease in the conversion rate of apo- into holo-ferredoxin was in the same range as for glycerol-grown cells, indicating that the extent of the defect in Fe-S protein assembly is similar under different physiological conditions. These data show that frataxin is not essential for Fe-S protein assembly, but improves the efficiency of the process. The large variations observed in the activity of Fe-S cluster proteins under different physiological conditions result from secondary defects in the physiology of delta YFH1 cells.
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PMID:A non-essential function for yeast frataxin in iron-sulfur cluster assembly. 1235 89

Frataxin is a mitochondrial protein with a central role in iron homeostasis. Defects in frataxin function lead to Friedreich's ataxia, a progressive neurodegenerative disease with childhood onset. The function of frataxin has been shown to be closely associated with its ability to form oligomeric species; however, the factors controlling oligomerization and the types of oligomers present in solution are a matter of debate. Using small-angle X-ray scattering, we found that Co(2+), glycerol, and a single amino acid substitution at the N-terminus, Y73A, facilitate oligomerization of yeast frataxin, resulting in a dynamic equilibrium between monomers, dimers, trimers, hexamers, and higher-order oligomers. Using X-ray crystallography, we found that Co(2+) binds inside the channel at the 3-fold axis of the trimer, which suggests that the metal has an oligomer-stabilizing role. The results reveal the types of oligomers present in solution and support our earlier suggestions that the trimer is the main building block of yeast frataxin oligomers. They also indicate that different mechanisms may control oligomer stability and oligomerization in vivo.
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PMID:Oligomerization propensity and flexibility of yeast frataxin studied by X-ray crystallography and small-angle X-ray scattering. 2205 11