Structure and analysis of the human dimethylglycine dehydrogenase gene

被引:15
作者
Binzak, BA
Vockley, JG
Jenkins, RB
Vockley, J
机构
[1] Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Biochem & Mol Biol, Rochester, MN 55905 USA
[2] Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Med Genet, Rochester, MN 55905 USA
[3] Mayo Clin & Mayo Fdn, Mayo Grad Sch, Dept Med Genet, Rochester, MN 55905 USA
[4] Mayo Clin & Mayo Fdn, Mayo Grad Sch, Dept Biochem & Mol Genet, Rochester, MN 55905 USA
[5] SmithKline Beecham, King Of Prussia, PA 19406 USA
[6] Mayo Clin & Mayo Fdn, Dept Lab Med, Rochester, MN 55905 USA
关键词
D O I
10.1006/mgme.2000.2980
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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, (C) 2000 Academic Press.
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页码:181 / 187
页数:7
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