Sphingolipid disorders

In aqueous systems, membrane lipids may exist in a gel-like solid state or as a two-dimensional liquid. In the case of pure phospholipids, these states interconvert at a well-defined transition temperature, Tc, that increases with alkyl chain length and decreases with introduction of alkyl chain unsaturation. In cell membranes, which have marked heterogeneity in both the polar and nonpolar domains of the bilayer, this state is described as liquid disordered . The presence of sufficient sphingolipids, with... 

B. Kaufman, 8. Basu, and S. Roseman, in 8. M. Aronson and B. N. Volk (Eds.), Inborn Disorders of Sphingolipid Metabolism, Proc.. Int. Symp. Cerebral Sphin-golipidoses, 3rd, Pergamon Press, Oxford and New York, 1966, pp. 193-213. 

Table 4.4.1 Enzyme and protein deficiencies and the associated sphingolipid storage disorders. D Dried blood spot, F fibroblasts, L leukocytes,... 

Milk fat contains several compounds that have demonstrated anticancer activity in animal models. The more important ones are rumenic acid, a potent inhibitor of mammary tumorigenesis, sphingomyelin and other sphingolipids that prevent the development of intestinal tumors and butyric acid, which prevents colon and mammary tumor development. Emerging evidence suggests that milk fat can prevent intestinal infections, particularly in children, prevent allergic disorders, such as asthma and improve the level of long-chain co-3 polyunsaturated fatty acids in blood. 

Tay-Sachs disease. A member of a family of disorders identified as the Gm2 gangliosidoses. As neural cell membranes are enriched in Gm2 gangliosides, the inability to degrade this class of sphingolipid resnlts in neural cell death. In addition to Tay-Sachs disease the family includes the Sandhoff diseases and the Gm2 activator deficiencies. Tay-Sachs disease resnlts from defects in the HEXA gene encoding the a-subunit of /3-hexosaminidase. 

Synthesis of glycosphingolipids and sulfoglycosphin-golipids involves the addition of sugar and sulfate residues to ceramide from UDP-sugar derivatives or the activated sulfate donor 3 -phosphoadenosine-5 -phosphosulfate (Chapter 17), and appropriate transferases. These pathways are discussed in Chapter 16. Catabolism of sphingolipids is by specific lysosomal hydrolases. Several inherited disorders associated with the deficiencies of these enzymes are discussed below. 

Austin, J. H., Some recent findings in leukodystrophies and in gargoylism. In Inborn Disorders of Sphingolipid Metabolism (S. N. Aronson and B. W. Volk, eds.), pp. 359-387. Pergamon, New York, 1967. 

Moser, H. W., Sugita, M., Harbison, M. D., and Williams, M. Liver glycolipid steroid sulfates and steroid sulfatases in a form of metachromatic leukodystrophy associated with multiple sulfatase deficiencies. In Sphingolipids, Sphingolipidosis, and Allied Disorders (D. W. Volk, and S. M. Aronson, eds.), pp. 429-450, Plenum, New York, 1972. 

Wenger, D. A., and Inui, K., Studies on the sphingolipid activator protein for the enzymatic hydrolyses of CMj ganglioside and sulfatide. In Molecular Basis of Lysosomal Storage Disorders (J. A. Barranger and R. O. Brady, eds.), pp. 61-78. Academic Press, Orlando, 1984. 

A Clinical Perspective Disorders of Sphingolipid Metabolism Steroids... 

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