Patients homozygous for the T435N mutation of succinyl-CoA:3-ketoacid CoA transferase (SCOT) do not show permanent ketosis
Patients homozygous for the T435N mutation of succinyl-CoA:3-ketoacid CoA transferase (SCOT) do not show permanent ketosis
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DOI：
10.1203/01.pdr.0000145297.90577.67
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发表时间：
2004-12-01
影响因子：
3.6
通讯作者：
Kondo, N
中科院分区：
文献类型：
--
作者：
Fukao, T;Shintaku, H;Kondo, N
琥珀酰-CoA：3-酮酸CoA转移酶（SCOT;基因座符号OXCT; E. C. 2.8.3.5）是组织解酮能力的主要决定因素。遗传性SCOT缺乏症可引起发作性酮症酸中毒。永久性酮症被认为是SCOT缺乏症的一个特征。在日本的一个小地区有三名SCOT缺乏患者，他们没有表现出永久性酮症，即使他们的酮症酸中毒危机与其他SCOT缺乏患者一样严重。这三个人都是T435 N突变的纯合子。野生型和突变体cDNA的瞬时表达分析表明，T435 N突变体保留了显著的残余SCOT活性（在39.5 ℃为野生型的20%，在37 ℃为25%，在30 ℃为50%）。在表达分析中，在这些温度下残留SCOT活性的差异是由于突变蛋白水平的差异。T435 N蛋白的SCOT活性比野生型更容易受到42 ℃和55 ℃热处理的影响。突变蛋白的这些温度敏感特性可以部分解释为什么患者在发热性疾病期间发生酮症酸中毒危机。在SCOT缺陷患者保留一些残余活动，永久酮症可能不存在。
Succinyl-CoA:3-ketoacid CoA transferase (SCOT; locus symbol OXCT; E.C. 2.8.3.5) is the main determinant of the ketolytic capacity of tissues. Hereditary SCOT deficiency causes episodic ketoacidosis. Permanent ketosis has been regarded as a pathognomonic feature of SCOT deficiency. There are three SCOT-deficient patients from a small region in Japan and they have not manifested permanent ketosis, even though their ketoacidotic crises were as severe as those of other SCOT-deficient patients. All three were homozygous for the T435N mutation. Transient expression analysis of wild-type and mutant cDNA showed that the T435N mutant retained significant residual SCOT activities (20% for that of the wild-type at 39.5degreesC, 25% at 37degreesC, and 50% at 30degreesC). The difference of residual SCOT activities at these temperatures in expression analyses was due to differences in the level of the mutant protein. SCOT activity of the T435N protein was more vulnerable than the wild-type to heat treatment at 42degreesC and 55degreesC. These temperature-sensitive characteristics of the mutant protein may explain, in part, why the patients developed ketoacidotic crises during febrile illness. In SCOT-deficient patients retaining some residual activity, permanent ketosis may be absent.