Sarcosine dehydrogenase

Related Reading

Introductions

Sarcosine dehydrogenase (SarDH) is a mitochondrial flavoproteinase involved in the oxidative degradation of choline to glycine. Lack of SarDH activity in humans is genetically transmitted and is responsible for the disorder of amino acid metabolism known as sarcosineemia. Sarcosine dehydrogenase catalyzes the chemical reaction of sarcosine N-demethylation to produce glycine. This enzyme is a mitochondrial enzyme that belongs to a family of oxidoreductases, particularly those that act on the CH-NH moiety of donors and other acceptors. This sarcosine dehydrogenase is closely related to dimethylglycine dehydrogenase, which catalyzes the dimethylglycine demethylation reaction to produce sarcosine. Both sarcosine dehydrogenase and dimethylglycine dehydrogenase use FAD as a cofactor. Sarcosine dehydrogenase is linked to the respiratory redox chain via electron transfer flavoprotein (ETF).

Structure

There is no crystal structure available for sarcosine dehydrogenase. Sarcosine dehydrogenase contains a covalently bound FAD group attached to the imidazole N(3) of the histidine residue via the 8 alpha position of the isoxazine ring. This enzyme also contains non-heme iron at a ratio of 1 or 2 Fe per 300,000 g of enzyme, and 0.5 mol of acid-soluble sulfur suggesting that electron transfer in the first step of the reaction may proceed in a different way than the Fe-S cluster.

Function

Sarcosine dehydrogenase is one of the enzymes in sarcosine metabolism that catalyzes the demethylation of sarcosine to produce glycine. It is preceded by dimethylglycine dehydrogenase that converts dimethylglycine to sarcosine. Glycine can also be converted to sarcosine by glycine N-methyltransferase. Since glycine is the product of a reaction catalyzed by sarcosine dehydrogenase, in addition to sarcosine metabolism, the enzyme indirectly links the creatine cycle and respiratory chain in the mitochondria.

Related Disease

• Sarcosinemia

Sarcosinemia (SAR), also known as hyperosinemia and SARDH deficiency, is a rare autosomal recessive genetic metabolic disorder characterized by elevated plasma and urine concentrations of sarcosine. It may be caused by an inborn error in sarcosine metabolism or by a severe folate deficiency associated with the conversion of sarcosine to glycine, which is required for the conversion of sarcosine to glycine. It is considered to be a relatively benign disorder. Sarcosinemia is thought to be caused by a mutation in the sarcosine dehydrogenase (SARDH) gene located on human chromosome 9q34. The disorder is inherited in an autosomal recessive manner, which means that the defective gene causing the disorder is located on an autosome (chromosome 9 is autosomal) and that two copies of the defective gene (one inherited from each parent) are required to be born with the disorder. People with autosomal recessive disorders have parents who carry a copy of the defective gene, but usually do not show any signs or symptoms of the disorder.

• Prostate cancer

In addition to sarcosineemia, sarcosine dehydrogenase appears to play a role in the progression of prostate cancer. As prostate cancer progresses, the concentrations of sarcosine, as well as uracil, kynurenine, glycerol 3-phosphate, leucine and proline, increase. Therefore, sarcosine can be used as a potential biomarker for detecting prostate cancer and measuring disease progression. Sarcosine dehydrogenase and other enzymes in the sarcosine metabolic pathway may be potential therapeutic targets for prostate cancer.