Structure and analysis of the human dimethylglycine dehydrogenase gene

Barbara A. Binzak, Joseph G. Vockley, Robert Brian Jenkins, Jerry Vockley

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)181-187
Number of pages7
JournalMolecular Genetics and Metabolism
Volume69
Issue number3
DOIs
StatePublished - Mar 2000

Fingerprint

Sarcosine
Genes
Polymorphism
Dimethylglycine Dehydrogenase
Sarcosine Dehydrogenase
Enzymes
Alleles
Inborn Errors Metabolism
Flavin-Adenine Dinucleotide
Coenzymes
Odors
Chromosomes
Choline
Fluorescence In Situ Hybridization
Folic Acid
Metabolism
Glycine
Fish
Haplotypes
Formaldehyde

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

Cite this

Structure and analysis of the human dimethylglycine dehydrogenase gene. / Binzak, Barbara A.; Vockley, Joseph G.; Jenkins, Robert Brian; Vockley, Jerry.

In: Molecular Genetics and Metabolism, Vol. 69, No. 3, 03.2000, p. 181-187.

Research output: Contribution to journalArticle

Binzak, Barbara A. ; Vockley, Joseph G. ; Jenkins, Robert Brian ; Vockley, Jerry. / Structure and analysis of the human dimethylglycine dehydrogenase gene. In: Molecular Genetics and Metabolism. 2000 ; Vol. 69, No. 3. pp. 181-187.
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