Sarcosine dehydrogenase is a liver mitochondrial matrix flavoenzyme that is defective in patients with
sarcosinemia, a rare autosomal metabolic defect characterized by elevated levels of
sarcosine in blood and urine. Some patients also exhibit
mental retardation and growth failure. A full-length
cDNA for human
sarcosine dehydrogenase was isolated from an adult liver cDNA library. The first 22 residues in the deduced amino acid sequence exhibit features expected for a mitochondrial targeting sequence. The predicted mass of the mature human liver
sarcosine dehydrogenase (99,505 Da) is in good agreement with that observed for rat liver
sarcosine dehydrogenase ( approximately 100,000 Da). Human
sarcosine dehydrogenase exhibits 89% identity with rat liver
sarcosine dehydrogenase and strong homology ( approximately 35% identity) with rat liver
dimethylglycine dehydrogenase, a
sarcosine dehydrogenase-related
protein from Rhodobacter capsulatus, and the regulatory subunit from bovine
pyruvate dehydrogenase phosphatase. The human
sarcosine dehydrogenase gene is at least 75.3 kb long and located on chromosome 9q34. The adult human liver clone is assembled from 21 exons (1-6, 7a, 8a, 9-21). Two smaller
cDNA clones, isolated from adult liver and infant brain libraries, were assembled from the same
sarcosine dehydrogenase gene by the use of alternate polyadenylation and splice sites. This is the first report of the genomic structure of the
sarcosine dehydrogenase gene in any species. The observed chromosomal location is consistent with genetic studies with a mouse model for
sarcosinemia that map the mouse gene to a region of mouse chromosome 2 syntenic with human 9q33-q34. The availability of the SDH gene sequence will enable characterization of the genotypes of
sarcosinemia patients with different phenotypes.