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Summary
Sulfatide is a glycosphingolipid found in the neural tissue and islets of Langerhans. Sulfatide preserves the insulin crystals, it acts as molecular chaperons for insulin, it facilitates its instant monomerisation and secretion. Sulfatide is primarily produced in a recycling pathway in beta cells. Arylsulphatase A (ASA) catalyzes the hydrolysis of sulfatide in lysosomes. In this study we investigate the possible interference of arylsulfatase A activity with sulfatide deficiency causing the metabolic and neurodegenerative aspects of diseases such as type 2 Diabetes Mellitus, Parkinson's disease, dementia and renal failure with hemodialysis treatment. We determined the ASA activity through spectrophotometry. The method of enzyme dosage is based on a 4 hour long hydrolysis of the ASA enzyme on 4-nitrocatechol sulfate (p-NCS) substrate. The unit of measurement used for the ASA substrate concentration p-NCS is nmol/ml/4h. Since we know the importance of sulfatide in type 2 Diabetes Mellitus and the great ASA enzyme activity variation in these patients, it is most probably the arylsulphatase A activity plays an important role in the evolution of the disease. Also, our findings indicate a possible causality between low arylsulphatase A activity and development of several neuropsychiatric disorders related to Parkinson's disease and Dementia, through cessation of precursor-making for sulfatide biosynthesis.
Keywords: arylsulphatase A, sulfatide, Type 2 Diabetes, Dementia, Parkinson's disease, hemodialysis
Introduction
Arylsulphatase A (ASA) is a lysosomal enzyme that catalyzes the hydrolysis of sulfatide (Eckhardt, 2008). Due to this enzyme deficiency, sulfatide accumulates within the lysosomes of various tissues (Blomqvist et al., 2011), therefore it can no longer fulfill its physiological functions.
Sulfatide is a multifunctional molecule for various biological fields including the nervous system, insulin secretion, immune system, hemostasis/thrombosis, bacterial and viral infection (Takahasi and Suzuki, 2012).
Sulfatide preserves the insulin crystals, it acts as molecular chaperons for insulin, it facilitates its instant monomerisation and secretion (Buschard et al., 2005). The buildup of the sulfatides consequent of ASA deficiency is associated with the breakdown of the myelin membrane involving several mechanisms (Ballabio and Gieselmann, 2009), causing a diffuse cerebral demyelinisation.
As Takahasi summarizes, "sulfatide is synthesized by two transferases (ceramide galactosyltransferase and cerebroside sulfotransferase) from ceramide and is specifically degraded by arylsulfatase A" (Takahasi and Suzuki, 2012). The molecules that result from ASA activity are...