Kassovska-Bratinova S, Fukao T, Song X Q, Duncan A M, Chen H S, Robert M F, Pérez-Cerdá C, Ugarte M, Chartrand C, Vobecky S, Kondo N, Mitchell G A
Service de Génétique Médicale, Hôpital Sainte-Justine, Montréal, Québec, Canada.
Am J Hum Genet. 1996 Sep;59(3):519-28.
Succinyl CoA: 3-oxoacid CoA transferase (SCOT; E.C.2.8.3.5) mediates the rate-determining step of ketolysis in extrahepatic tissues, the esterification of acetoacetate to CoA for use in energy production. Hereditary SCOT deficiency in humans causes episodes of severe ketoacidosis. We obtained human-heart SCOT cDNA clones spanning the entire 1,560-nt coding sequence. Sequence alignment of the human SCOT peptides with other known CoA transferases revealed several conserved regions of potential functional importance. A single approximately 3.2-kb SCOT mRNA is present in human tissues (heart > leukocytes >> fibroblasts), but no signal is detectable in the human hepatoma cell line HepG2. We mapped the human SCOT locus (OXCT) to the cytogenetic band 5p13 by in situ hybridization. From fibroblasts of a patient with hereditary SCOT deficiency, we amplified and cloned cDNA fragments containing the entire SCOT coding sequence. We found a homozygous C-to-G transversion at nt 848, which changes the Ser 283 codon to a stop codon. This mutation (S283X) is incompatible with normal enzyme function and represents the first documentation of a pathogenic mutation in SCOT deficiency.
琥珀酰辅酶A：3-氧代酸辅酶A转移酶（SCOT；E.C.2.8.3.5）介导肝外组织中酮体分解的限速步骤，即将乙酰乙酸酯化为辅酶A以供能量产生之用。人类遗传性SCOT缺乏会导致严重酮症酸中毒发作。我们获得了跨越整个1560个核苷酸编码序列的人心肌SCOT cDNA克隆。将人类SCOT肽与其他已知辅酶A转移酶进行序列比对，发现了几个具有潜在功能重要性的保守区域。在人类组织（心脏>白细胞>>成纤维细胞）中存在单一的约3.2 kb的SCOT mRNA，但在人肝癌细胞系HepG2中未检测到信号。我们通过原位杂交将人类SCOT基因座（OXCT）定位到细胞遗传学带5p13。从一名遗传性SCOT缺乏患者的成纤维细胞中，我们扩增并克隆了包含整个SCOT编码序列的cDNA片段。我们在第848位核苷酸处发现了一个纯合的C到G的颠换，该颠换将丝氨酸283密码子变为终止密码子。这种突变（S283X）与正常酶功能不相容，是SCOT缺乏致病突变的首次记录。
