ジヒドロリポアミド・スクシニル転移酵素の構造と機能 : 新しい展開をめざして

概要

論文の詳細を見る
A family of α-ketoacid dehydrogenase complex includes α-ketoglutarate dehydrogenase (α-KGDC), pyruvate dehydrogenase and branched chain α-ketoacid dehydrogenase complexes. These three complexes are composed of three different component enzymes, α-ketoacid decarboxylase (E1), dihydrolipoamide acyltransferase (E2) and dihydrolipoamide dehydrogenase (E3). We isolated and sequenced cDNA clones for the dihydrolipoamide succinyltransferase (E2 of α-KGDC, designated as DLST) components of the rat and human α-KGDCs. The primary structures of the rat and human DLSTs showed close similarity to those of E. coll and A. vinelandii DLSTs. However, theratandhumanDLSTsdidnotcontainasequencemotifthathadbeenfoundasanE3 and/or E1 binding domain in the E2 components of three α-ketoacid dehydrogenase complexes, suggesting the lack of the E3 and/or E1 binding domain in the rat and human DLSTs. The result of phylogenetic tree of the E2 components of three complexes demonstrated that the lack of the domain in rat and human DLSTs might occur after the mitochondrial symbiosis. Next, we isolated genomic DNA and processed pseudogene of human DLST and determined their entire nucleotide sequences. In situ hybridization analysis demonstrated that the human DLST gene is located on chromosome 14 at q24.2-q24.3 and the pseudogene is located on chromosome 1 at p31. The results of CAT and gel shift assays showed that another protein rather than Sp1 plays a significant role with Ap2 in the transcription-regulation of DLST gene. In addition, we detected polymorphisms in the human DLST gene and found an association of a genotype (ac/ac type) of DLST gene with Alzheimer's disease. Furthermore, we have observed that in the skeletal muscle the DLST is also localized on the plasma membrane and sarcoplasmic reticulum and that the molecule (25 kDa) is smaller than mitochondrial DLST (48 kDa).
日本ビタミン学会の論文
2000-08-25

ジヒドロリポアミド・スクシニル転移酵素の構造と機能 : 新しい展開をめざして

スポンサーリンク

概要

著者

関連論文

スポンサーリンク