Metabolism of sphingolipids

Figure 21-6 Pathways of synthesis and metabolism of sphingolipids. Gray arrows indicate catabolic pathways. See also Fig. 20-11. The green extension on the ceramide structure is that of a long-chain co-hydroxyceramide that is covalently bound to protein in human skin.

Teles JH, Breuer K, Enders D, Gielen H (1999) One pot synthesis of 3,4-disubstituted l-alkyl-4H-l,2,4-triazol-l-ium salts. Synth Commun 29 1-9 Thorpe SR, Sweeley C (1967) Chemistry and metabolism of sphingolipids. On the biosynthesis of phytosphingosine by yeast. Biochemistry 6 887... 

Intracellular Transport of Membrane Phospholipids Metabolism of Sphingolipids (Figure 19.13, Figure 19.14, Table 19.1, Figure 19.16) Steroid Metabolism... 

This section will address the most commonly used experimental approaches and tools that are available to probe ceramide-mediated functions. It should be noted at the outset that the interconnected metabolism of sphingolipids complicates the study of ceramide bioactivity, since ceramide participates in a network of metabolic pathways that connect several bioactive lipids, including sphingosine, sphingosine-1-phosphate, diacylglycerol and others. 

Figure 1. Scheme of sphingolipid metabolism and the central role of ceramide and ceramidases. 

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. 

Vitamin B6 occurs naturally in three related forms pyridoxine (6.26 the alcohol form), pyridoxal (6.27 aldehyde) and pyridoxamine (6.28 amine). All are structurally related to pyridine. The active co-enzyme form of this vitamin is pyridoxal phosphate (PLP 6.29), which is a co-factor for transaminases which catalyse the transfer of amino groups (6.29). PLP is also important for amino acid decarboxylases and functions in the metabolism of glycogen and the synthesis of sphingolipids in the nervous system. In addition, PLP is involved in the formation of niacin from tryptophan (section 6.3.3) and in the initial synthesis of haem. 

Sphingolipids were first described in a remarkable treatise on the chemical constitution of the brain by Johann L. W. Thudichum, a physician-scientist in London, who published his findings more than 100 years ago. A major impetus for the study of the chemistry and metabolism of the sphingolipids was the discovery of several rare human diseases that could be attributed to the abnormal accumulation of sphingolipids. This accumulation has been shown to result from a defect in catabolism that normally occurs in lysosomes. It is now known that many different kinds of sphingolipids exist, and more than 300 structures have been reported to occur in nature. 

Hanada K. (2003). Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim. Biophys. Acta 1632 16-30. 

During the past decade, several reports have demonstrated the decline of sphingolipid metabolism in atopic dermatitis24,25 and the cause of dry skin has been shown to be the abnormality of sphingolipid metabolism.26 However, in experimentally induced dry skin, the total amount of SC ceramide did not change13,26 but the amino acid content decreased.13 Recently, Tanaka etal. reported27 that amino acid content was reduced in the SC in atopic respiratory disease. They suggested that the free amino acid content is the crucial factor of the dry, scaly features of not only experimentally induced... 

Delgado A, Casas J, Llebaria A, Abad JL, Fabrias G. Inhibitors of sphingolipid metabolism enzymes. Biochim. Biophys. Acta 2006 1758 1957-1977. 

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