Disease relevance of Dld

• IC50s were determined by BrdU cell growth assay after short time as well as long term exposure of the following cell lines: human endothelial cells (HdmVEC/HUVEC), human breast cancer (Mcf-7), melanoma (Skmel), liver cancer (Huh7/Alexander), lung cancer (A549/LXFL), colon cancer (Dld) and murine renal cell carcinoma (RENCA) [1].
• The aim of this study was to investigate liver histology in mice after immunization with the conserved self molecule dihydrolipoamide dehydrogenase, E3, a subunit of the mitochondrial 2-OADC enzyme family identified as the M2 autoantigen in the liver disease, primary biliary cirrhosis [2].

High impact information on Dld

• Novelty of the pyruvate metabolic enzyme dihydrolipoamide dehydrogenase in spermatozoa: correlation of its localization, tyrosine phosphorylation, and activity during sperm capacitation [3].
• The capacitation-dependent time course of tyrosine phosphorylation of dihydrolipoamide dehydrogenase appears to be different in the principal piece of the flagella and the acrosome in hamster spermatozoa [3].
• We have shown earlier that dihydrolipoamide dehydrogenase, a post-pyruvate metabolic enzyme, undergoes capacitation-dependent tyrosine phosphorylation, and the functioning of the enzyme is required for hyperactivation (enhanced motility) and acrosome reaction of hamster spermatozoa (Mitra, K., and Shivaji, S. (2004) Biol. Reprod. 70, 887-899) [3].
• The localization of dihydrolipoamide dehydrogenase, however, appears to be in the mitochondria in the spermatocytes, but in spermatids it appears to show a juxtanuclear localization (like Golgi) [3].
• This is the first report of a direct correlation of the localization, tyrosine phosphorylation, and activity of the important metabolic enzyme, dihydrolipoamide dehydrogenase, implicating dual involvement and regulation of the enzyme during sperm capacitation [3].

Biological context of Dld

• The Dld gene is contained within an approximately 21-kb region and consists of 14 exons ranging in size from 69 to 521 nucleotides [4].
• The Dld gene has been localized to the proximal region of chromosome 12, approximately 21 cM from the centromere [4].
• To identify further the cis elements involved in transcription of the Dld gene (-82 bp to +41 bp), a series of mutations were introduced into this region and evaluated for functional effects using transient transfection and electrophoretic mobility shift assays [5].
• Roles of an Ets motif and a novel CACGAC direct repeat in transcription of the murine dihydrolipoamide dehydrogenase (Dld) gene [5].

Anatomical context of Dld

• In hamster spermatozoa, dihydrolipoamide dehydrogenase along with its host complex, the pyruvate dehydrogenase complex, are localized in the acrosome and in the principal piece of the sperm flagella [3].
• Induction of dihydrolipoamide dehydrogenase in 3T3-L1 cells during differentiation [6].
• The activity and turnover of dihydrolipoamide dehydrogenase (E3), the common component of the three 2-oxoacid dehydrogenase complexes, were measured during the differentiation of 3T3-L1 preadipocytes into 3T3-L1 adipocytes [6].

Associations of Dld with chemical compounds

• We also measured H(2)O(2) production by brain mitochondria isolated from heterozygous knock-out mice deficient in dihydrolipoyl dehydrogenase (Dld) [7].

Analytical, diagnostic and therapeutic context of Dld

• Northern blot analysis shows that the Dld mRNA in various tissues is approximately 2.4 kb in size [4].

References