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Pathway Description
Sarcosinemia
Homo sapiens
Disease Pathway
Created: 2022-10-24
Last Updated: 2023-10-25
Sarcosinemia (SAR), also known as hypersarcosinemia, sarcosine dehydrogenase complex deficiency, SARDH deficiency, SARDHD or SARD deficiency, is an autosomal recessive metabolic disorder leading to increased levels of the amino acid sarcosine in blood plasma, as well as increased levels of sarcosine excreted in urine. SAR can be caused by a mutation, either homozygous or compound heterozygous, in the SARDH gene which codes for the sarcosine dehydrogenase enzyme. This enzyme converts sarcosine to glycine, and its absence leads to an increase in the amount of sarcosine in the body. It can also potentially be caused by a lack of folate, as folate is used in the sarcosine dehydrogenase reaction, and even with a working enzyme, the lack of substrates can prevent the conversion from occurring, leading to the same effects. The condition has been associated with mental and motor retardation, visual impairment, however other cases have been detected with no mental or physical abnormalities other than increased sarcosine levels, so it is possible that the defect is benign, or that there exist some phenotypes that are more severe than others, or unknown disorders present in the cases showing symptoms. Sarcosine can be formed from a series of reactions starting with trimethylglycine. This, along with homocysteine, react using betaine-homocysteine S-methyltransferase to form L-methionine, as well as dimethylglycine. The dimethylglycine then enters the mitochondrial matrix, and interacts with dimethylglycine dehydrogenase along with a water molecule, forming formadehyde and sarcosine. Sarcosine can also be formed in a reversible reaction from S-adenosylmethionine and glycine, using glycine N-methyltransferase as the enzyme, and forming S-adenosylhomocysteine as another product. Normally, sarcosine can interact with sarcosine dehydrogenase in the mitochondria, forming both formaldehyde and glycine. However, in this disorder, the gene encoding sarcosine dehydrogenase has been mutated and the protein is not produced, preventing this reaction from occurring. This leads to an increased concentration of sarcosine, which leads to the effects of the condition.
References
Sarcosinemia References
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