Sphingomyelin, biosynthesis

Figure 24-8. Biosynthesis of sphingomyelin (A), galactosylceramide and its sulfo derivative (B). (PAPS, "active sulfate," adenosine 3 -phosphate-5 -phospho-sulfate.)...

Wieder, T., PerUtz, C., Wieprecht, M., Huang, R.T., Geilenm C.C. and Orfanosm, CR., 1995, Two new sphingomyelin analogs inhibit phosphatidylcholine biosynthesis by decreasing membrane-bound CTP phosphocholine cytidylyltransferase levels in HaCaT cells. Biochem. J. 311 873-879... 

It was also demonstrated that ceramides derived from sphingomyelin breakdown mediated by ASM are used for ganglioside biosynthesis, up to the generation of GD3. Indeed, lymphoblastoid cells derived from Niemann-... 

FIGURE 21-31 Biosynthesis of sphingolipids. Condensation of palmitoyl-CoA and serine followed by reduction with NADPH yields sphinganine, which is then acylated to N-acylsphinganine (a ceramide). In animals, a double bond (shaded pink) is created by a mixed-function oxidase, before the final addition of a head group phosphatidylcholine, to form sphingomyelin glucose, to form a cerebroside. 

Lysophospholipids have been found in butter serum by Cho et al. (1977). They characterized the sn-1 and -2 lysophosphatidylcholines and phosphatidylethanolamines. It is not known if these compounds are products of degradation or remnants of biosynthesis. Cho et al. (1977) searched for, but did not find, another possible product of enzymatic degradation of milk, phosphatidic acid. Phosphatidic acid can be formed by the action of phospholipase D on phosphatidylcholine, for example, but this enzymatic activity was not detected. The compound is also an important intermediate in the biosynthesis of lipids, but the concentration in tissue is always very low. The amount is also low in milk. Cho et al. (1977) found 1.2 and 0.9 (percent of total lipid P) of the lyso compounds above. The quantities of the other phospholipids were phosphatidylethanolamine, 27.3 -choline, 29.1 -serine, 13.4 -inositol, 2.5 and sphingomyelin, 25.6. 

Figure 9.18 Structures of sphinogosine (A), a sphingomyelin (B), a glucocerebroside (C), and a ganglioside (D). In the last, stearic acid is attached to the -NH2 residue of sphingosine. The structure shown represents a GMj ganglioside. (Parts A, B, C reproduced by permission from Diem K, Lentner C. Scientific Tables. Basel Ciba-Geigy, 1971, p. 376 part D reproduced with permission from Fishman PH, Brady RO. Biosynthesis and function of gangliosides. Science 194 906-915, 1976.

Sphingolipids comprise glycolipids (gangliosides and cerebrosides) and the phospholipid, sphingomyelin. These compounds, too, are important membrane constituents. The biosynthesis of sphingolipids involves the common intermediate ceramide (Fig. 13-15). 

Membrane proteins have a unique orientation because they are synthesized and inserted into the membrane in an asymmetric manner. This absolute asymmetry is preserved because membrane proteins do not rotate from one side of the membrane to the other and because membranes are always synthesized by the growth of preexisting membranes. Lipids, too, are asymmetrically distributed as a consequence of their mode of biosynthesis, but this asymmetry is usually not absolute, except for glycolipids. In the red-blood-cell membrane, sphingomyelin and phosphatidyl choline are preferentially located in the outer leaflet of the bilayer, whereas phosphatidyl ethanolamine and phosphatidyl serine are located mainly in the inner leaflet. Large amounts of cholesterol are present in both leaflets. 

Asymmetry. Biological membranes are asymmetric that is, the lipid composition of each half of a bilayer is different. For example, the human red blood cell membrane possesses substantially more phosphatidylcholine and sphingomyelin on its outside surface. Most of the membrane s phosphatidylserine and phos-phatidylethanolamine are on the inner side. Membrane asymmetry is not unexpected, because each side of a membrane is exposed to a different environment. Asymmetry originates during membrane synthesis, because phospholipid biosynthesis occurs on only one side of a membrane (Special Interest Box 12.3). The protein components of membranes (discussed below) also exhibit considerable asymmetry with distinctly different functional domains within membrane and on the cytoplasmic and extracellular faces of membrane. 

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