Sulfatide, also known as 3-O-sulfogalactosylceramide, SM4, or sulfated galactocerebroside, is a class of sulfolipids, specifically a class of sulfoglycolipids, which are glycolipids that contain a sulfate group. 3- O-sulfogalactosylceramide is the first sulfoglycolipid isolated from the human brain and was given the name sulfatide by Thudichum in 1884.
Figure. Structure of sulfatide.
Sulfatide synthesis begins with a reaction between UDP-galactose and 2-hydroxylated or non-hydroxylated ceramide. This reaction is catalyzed by galactosyltransferase (CGT), where galactose is transferred to 2-hydroxylated, or non-hydroxylated ceramide, from UDP-galactose. This reaction occurs in the luminal leaflet of the endoplasmic reticulum, and its final product is GalCer, or galactocerebroside, which is then transported to the Golgi apparatus. Here, GalCer reacts with 3’-phosphoadenosine-5’-phosphosulfate (PAPS) to make sulfatide. This reaction is catalyzed by cerebroside sulfotransferase (CST). CST is a homodimeric protein that is found in the Golgi apparatus. It has been demonstrated that mice models lacking CST, CGT, or both are incapable of producing sulfatide indicating that CST and CGT are necessary components of sulfatide synthesis.
Degradation of sulfatides takes place in the lysosomes and is catalyzed by the lysosomal enzyme arylsulfatase A (ASA). An accessory protein saposin B, a socalled“sphingolipid activator protein,” is required for the lysosomal degradation of sulfatides by ASA. A deficiency of ASA or of saposin B leads to intralysosomal storage of sulfatides and is the cause of the lysosomal storage disease metachromatic leukodystrophy (MLD). Lysosulfatide, the deacylated form of sulfatides, also accumulates in tissues of patients with MLD. The accumulation of sulfatides in kidney leads to an increased excretion of sulfatides in urine. Determination of sulfatides in urine is a convenient diagnostic tool to confirm MLD in patients with arylsulfatase A deficiency or saposin B deficiency. In addition to mutation analysis of the ASA gene, it is also used to confirm a pseudo deficiency of arylsulfatase A. Severe demyelination is an important feature of MLD in humans. A mouse model of arylsulfatase A deficiency was created by targeted disruption of the ASA gene. This model was extensively characterized and exhibits many features of human MLD, including storage of sulfatides and lysosulfatide. However, in contrast to the human disease, this mouse model of MLD does not show demyelination. Demyelination could be induced in ASA knockout mice overexpressing CGT, presumably by increasing the substrate load in the lysosomes that lack the ability to degrade sulfatides.
Figure. Metabolism of sulfatide synthesis and degradation.
Several methods have been used to quantify sulfatides, including TLC, HPLC, and, more recently, MS. We Creative Proteomics describe a highly sensitive and reliable LC/MS/MS method to quantify sulfatides.
Identification and quantification of sulfatides
A detailed technical report will be provided at the end of the whole project, including the experiment procedure, MS/MS instrument parameters.
Analytes are reported as uM or ug/mg (tissue), and CV's are generally<10%.
The name of the analytes, abbreviation, formula, molecular weight and CAS# would also be included in the report.
With integrated set of separation, characterization, identification and quantification systems featured with excellent robustness & reproducibility, high and ultra-sensitivity, Creative Proteomics provides reliable, rapid and cost-effective sulfatides targeted metabolomics services.
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