Disease relevance of KGD1

• The encoded protein had 38% identical residues with the reported sequence of alpha-ketoglutarate dehydrogenase from Escherichia coli [1].

High impact information on KGD1

• Analysis of the KGD2 sequence revealed an open reading frame encoding a protein with a molecular weight of 52,375 and 42% identities to the KE2 component of Escherichia coli alpha-ketoglutarate dehydrogenase complex [2].
• Higher steady-state levels of KGD1 mRNA were detected in wild-type yeast grown on the nonrepressible sugar galactose than in yeast grown on high glucose [1].
• The sequence of the cloned region of DNA which complements kgd1 mutants was found to have an open reading frame of 3,042 nucleotides capable of coding for a protein of Mw 114,470 [1].
• Transformants containing the gene on a multicopy plasmid had three- to four-times-higher alpha-ketoglutarate dehydrogenase activity than did wild-type S. cerevisiae [1].
• Expression of hypoxic/anaerobic genes was elevated in alpha-ketoglutarate dehydrogenase mutants, whereas expression of oxidative genes was diminished, consistent with a heme signaling defect caused by inadequate levels of the heme precursor, succinyl-CoA [3].

Biological context of KGD1

• The two mutations were differentiated by the cloned suppressor gene which was able to partially complement ogd1, but not kgd1 [4].
• The results presented indicate that the Kgd1 and Lip5 proteins are important for the expression of genes encoding peroxisomal matrix proteins, although they are not necessary for the biogenesis of this cellular compartment [5].

Anatomical context of KGD1

• KGD1 triggered formation of the mitochondrial aggregates, because the latter were absent in a KGD1(-) mutant, but it did not efficiently do so in the cytosol [6].
• Furthermore, efficient clearance of the aggregated IRP1-KGD1 complex does not occur in the organelle, which emphasizes the role of molecular interactions in determining the fate of IRP1 [6].
• Alpha-Ketoglutarate dehydrogenase and lipoic acid synthase are important for the functioning of peroxisomes of Saccharomyces cerevisiae [5].

Associations of KGD1 with chemical compounds

• The mutation of one of these mutant strains with low succinate productivity was found to occur in the KGD1 gene [7].
• We found decreased activity of pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, and aconitase, while the rest of the citric acid cycle enzymes and oxidative enzymes did not change significantly [8].
• Consistent with this finding, a kgd1 mutant displayed lower levels of succinate production on glutamate than on other nitrogen sources, and higher levels of oxoglutarate dehydrogenase activity were observed on glutamate [9].
• The ogd1 and kgd1 mutants lacking 2-oxoglutarate dehydrogenase activity in yeast are allelic and can be differentiated by the cloned amber suppressor [4].
• Deletion of mitochondrial citrate synthase (CS1) protein resulted in changes in metabolites, decrease in the amounts of pyruvate and alpha-ketoglutarate dehydrogenase complexes, reduced mitochondrial respiration of citrate and isocitrate, and an inability to grow on acetate [10].

Other interactions of KGD1

• Two mutants were isolated; they are impaired in oleate utilisation and carry mutations in the KGD1 and LIP5 genes encoding the E1 component of the mitochondrial alpha-ketoglutarate dehydrogenase complex and lipoic acid synthase, respectively [5].

Analytical, diagnostic and therapeutic context of KGD1

• The complementation of the kdg1 mutant by the OGD1 gene, an allelism test, and meiotic mapping, revealed that the ogd1 and kgd1 mutations are allelic [4].

References