Structure and analysis of the human dimethylglycine dehydrogenase gene.
Structure and analysis of the human dimethylglycine dehydrogenase gene.
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DOI：
10.1006/mgme.2000.2980
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发表时间：
2000-03
影响因子：
3.8
通讯作者：
B. Binzak;J. Vockley;R. Jenkins;J. Vockley
中科院分区：
文献类型：
--
作者：
B. Binzak;J. Vockley;R. Jenkins;J. Vockley
二甲基甘氨酸脱氢酶（DMGDH; EC 1.5.99.2）是一种参与胆碱催化的酶，催化二甲基甘氨酸（DMG）的氧化去甲基化以形成肌氨酸。随后，肌氨酸脱氢酶（SDH; E.C. 1.5.99.1）通过类似的反应将肌氨酸转化为甘氨酸。这两种酶被发现作为单体在线粒体基质中，都含有1摩尔的共价结合的黄素腺嘌呤二核苷酸。DMGDH和SDH也利用非共价结合的叶酸辅酶，其接受被DMGDH和SDH去除的“1-碳”基团，形成“活性甲醛”。“我们最近描述了一种新的先天性DMGDH代谢缺陷，其特征是不寻常的鱼样体臭。为了加强我们对这种新疾病的研究，我们分离了两个人类基因组克隆，它们共同包含hDMGDH基因编码序列的16个外显子。hDMGDH基因的荧光原位杂交分析表明，它位于染色体5q12.2-q12.3上。此外，已在hDMGDH cDNA序列中鉴定出几种多态性。两个Ser/Pro多态性的人群分析发现，367个氨基酸分开揭示了等位基因的偏斜，与观察到的Ser/Ser或Pro/Pro等位基因的数量相比，单倍型Ser/Pro或Pro/Ser（79%）过度代表。这些研究结果可能的功能后果进行了讨论。hDMGDH基因结构的表征将有助于研究这种酶遗传缺陷的患者。
Dimethylglycine dehydrogenase (DMGDH; E.C. 1.5.99.2) is an enzyme involved in the catabolism of choline, catalyzing the oxidative demethylation of dimethylglycine (DMG) to form sarcosine. Subsequently, sarcosine dehydrogenase (SDH; E.C. 1.5.99.1) converts sarcosine to glycine via a similar reaction. Both enzymes are found as monomers in the mitochondrial matrix, and both contain 1 mol of covalently bound flavin adenine dinucleotide. DMGDH and SDH also utilize a noncovalently bound folate coenzyme that receives the "1-carbon" groups that are removed by DMGDH and SDH, forming "active formaldehyde." We have recently described a new inborn error of metabolism of DMGDH characterized by an unusual fish-like body odor. To augment our study of this new disorder, we have isolated two human genomic clones that together contain 16 exons of coding sequence for the hDMGDH gene. Fluorescent in situ hybridization analysis of the hDMGDH gene indicates that it is found on chromosome 5q12.2-q12.3. In addition, several polymorphisms have been identified in the hDMGDH cDNA sequence. Population analysis of two Ser/Pro polymorphisms found 367 amino acids apart reveals a skew of alleles, with the haplotypes Ser/Pro or Pro/Ser (79%) overrepresented compared to the number of Ser/Ser or Pro/Pro alleles observed. Possible functional consequences of these findings are discussed. Characterization of the gene structure for hDMGDH will aid in the study of patients with inherited defects of this enzyme.