Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase.
Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase.
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发表时间：
1988-10
影响因子：
9.8
通讯作者：
Soo-Sang Kang;Jeimin Zhou;P. Wong;J. Kowalisyn;G. Strokosch
中科院分区：
文献类型：
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作者：
Soo-Sang Kang;Jeimin Zhou;P. Wong;J. Kowalisyn;G. Strokosch
在两名血清叶酸低于正常的无关患者中发现了一种“新发现的”亚甲基四氢叶酸（MTHF）还原酶（E.C.1.1.1.68）缺陷变异体，与血浆总同型半胱氨酸升高8-15倍相关。但是，通过口服叶酸补充剂纠正了同型半胱氨酸血症。当淋巴细胞提取物中MTHF还原酶活性在46 ℃下热处理5分钟前后进行比较时，对照组和患者的酶之间的热稳定性存在一致的差异。热处理后，对照组的平均剩余活性为37.0%（34.1%-42.6%），两例患者分别为15.2%和15.1%。两个专性杂合子严重MTHF还原酶缺乏症的残留活动的39.6%和37.7%。在培养的皮肤成纤维细胞和成淋巴细胞中证明了热稳定性的类似差异。从控制和患者的淋巴母细胞提取物的混合物和部分纯化的酶的研究表明，热稳定性是MTHF还原酶的一个独立特征。这些观察结果提供了证据，迄今未描述的突变MTHF还原酶在我们的两个病人与中间同型半胱氨酸血症。与以前报道的MTHF还原酶缺乏症患者不同，这两名受试者在婴儿期或儿童期没有明显的与叶酸或同型半胱氨酸代谢异常相关的临床问题，但其中一人在成年期有血管疾病。在这两个主题的观察表明，中度缺乏MTHF还原酶可能与血管疾病的成年生活。
A "newly detected" variant of methylenetetrahydrofolate (MTHF) reductase (E.C.1.1.1.68) deficiency associated with an 8-15-fold increase in plasma total homocysteine was discovered in two unrelated patients who had subnormal serum folate. However, the homocysteinemia was corrected by oral folic acid supplement. When MTHF reductase activities in lymphocyte extracts before and after heat treatment at 46 C for 5 min were compared, there was a consistent difference in heat stability between the enzyme from the controls and that from the patients. The mean residual activities after heat treatment were 37.0% (34.1%-42.6%) in the controls and 15.2% and 15.1% in the two patients, respectively. Two obligate heterozygotes for severe MTHF reductase deficiency had residual activities of 39.6% and 37.7%. A similar difference in thermostability was demonstrated in cultured skin fibroblasts and lymphoblasts. Studies with a mixture of lymphoblast extracts from a control and a patient and with partially purified enzyme suggested that the thermostability was an independent characteristic of MTHF reductase. These observations provided evidence of a hitherto undescribed mutant MTHF reductase in our two patients with intermediate homocysteinemia. Unlike previously reported patients with MTHF reductase deficiency, there was no apparent clinical problem related to the abnormal folate or homocysteine metabolism during infancy or childhood in these two subjects, but one of them had vascular disorders in adulthood. The observations in these two subjects suggested that a moderate deficiency of MTHF reductase might be associated with vascular disorders in adult life.