Synthesis pathways sphingolipids

Rosenwald, A. G., Machamer, C. E., and Pagano, R. E. (1992). Effects of a sphingolipid synthesis inhibitor on membrane transport through the secretory pathway. Biochemistry 31, 3581-3590. 

The a-oxoamine synthases family is a small group of fold-type I enzymes that catalyze Claisen condensations between amino acids and acyl-CoA thioesters (Figure 16). Members of this family are (1) 8-amino-7-oxononanoate (AON) synthase (AONS), which catalyzes the first committed step in the biosynthesis of biotine, (2) 5-aminolevulinate synthase (ALAS), responsible for the condensation between glycine and succinyl-CoA, which yields aminolevulinate, the universal precursor of tetrapyrrolic compounds, (3) serine palmitoyltransferase (SPT), which catalyzes the first reaction in sphingolipids synthesis, and (4) 2-amino-3-ketobutyrate CoA ligase (KBL), involved in the threonine degradation pathway. With the exception of the reaction catalyzed by KLB, all condensation reactions involve a decarboxylase step. 

Futerman, AH (1994) An update of sphingolipid synthesis and transport along the secretory pathway. Trends Glycosci Glycotechnol, 6, 143-153. 

We turn now to the biosynthesis of lipid structures. We begin with a discussion of the biosynthesis of fatty acids, stressing the basic pathways, additional means of elongation, mechanisms for the introduction of double bonds, and regulation of fatty acid synthesis. Sections then follow on the biosynthesis of glyc-erophospholipids, sphingolipids, eicosanoids, and cholesterol. The transport of lipids through the body in lipoprotein complexes is described, and the chapter closes with discussions of the biosynthesis of bile salts and steroid hormones. 

The pathways for the synthesis of phosphoglycerides and sphingolipids are described in detail in Chapter 11. They are, therefore, described only in brief here in order to emphasise the importance of the essential fatty acids in proliferation and how the cell cycle could be impaired by failure to provide these acids. 

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.

Gillard, B. K., Clement, R. G., and Marcus, D. M., 1998, Variations among cell lines in the synthesis of sphingolipids in de novo and recycling pathways. Glycobiology 8 885-890. 

This chapter examines the biosynthesis of three important components of biological membranes—phospholipids, sphingolipids, and cholesterol (Chapter 12). Triacylglycerols also are considered here because the pathway for their synthesis overlaps that of phospholipids. Cholesterol is of interest both as a membrane component and as a precursor of many signal molecules, including the steroid hormones progesterone, testosterone, estrogen, and cortisol. The biosynthesis of cholesterol exemplifies a fundamental mechanism for the assembly of extended carbon skeletons from five-carbon units. 

Sphingolipid biosynthesis is catalyzed by membrane-bound enzymes of the endoplasmic reticulum. Sphingo-sine, an acylaminoalcohol, is synthesized from palmitoyl-CoA and serine in a reaction that requires pyridoxal phosphate, NADPH, and Mn + (Figure 19-7). The exact pathway of ceramide synthesis is not known. The acyl group may be added to the 2-amino group of sphinganine,... 

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. 

A genus of bacteria, termed the Sphingobacterium, produces sphingolipids by a pathway similar to that in mammals. Clostridia produce plasmalogens (l-alk-l -enyl lipids) by an anaerobic pathway clearly different from the Oj-dependent pathway in mammals (Chapter 9). Branched-chain fatty acids are also found in which the methyl group is inserted post-synthetically into the middle of the chain, in a manner analogous to cyclopropane fatty acid synthesis (Section 5.5). S-adenosylmethionine is also the methyl donor for these reactions. The biochemistry surrounding the formation of these and many other bacterial phospholipids remains to be elucidated. 

Recent studies have revealed that marine viruses encode unexpected and novel proteins which would not be expected to occur within a virus genome. For example, the giant algal viruses have been shown to encode novel glycosylases, potassium pumps, and a pathway for the synthesis of complex sphingolipids. This biochemical diversity indicates that marine viruses could be a rich source for exploitation in the future for new types of carbohydrate and lipid as well as new proteins and enzymes. 

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