Phosphatidylserine , metabolic

Materials. Egg phosphatidylcholine (PC), bovine brain phosphatidylserine (PS) were obtained from Avanti Polar Lipids Inc. (Birmingham, AL) and cholesterol was from Sigma (St. Louis, MO). Ganglioside GMj, bovine, was obtained from Calbiochem (San Diego, CA). Diethylenetriamine pentaacetic acid distearylamide complex (DPTA-SA) was synthesized according to ref. 17 and nlIn-DTPA-SA was prepared as described (7). This lipophilic radiolabel is not transferred to the serum components from liposomes (unpublished data), nor is it rapidly metabolized in vivo (7). The synthesis of N-(glutaryl)phosphatidylethanolamine(NGPE) has been described (18). Dipalmitoyl deoxyfluorouridine(dpFUdR) was synthesized as described (24). 

Today s mitochondria lack most of the genes involved in phosphohpid metabolism. Therefore, mitochondria have to import most of their hpids. Phospholipids such as phosphatidylcholine, phosphatidylserine, phosphatidylglycerol, and phosphatidylinositol must be synthesized in the endoplasmatic reticulum under the control of nuclear genes and then transferred to mitochondria (Voelker, 2000) (Figure 1). Mitochondria use both nuclear and mitochondrial encoded proteins to further diversify phospholipids (Dowhan, 1997 Kent, 1995 Daum, 1985). Thus, a nuclear phosphatidylserine decarboxylase converts phosphatidylserine into phosphatidylethanolamine, or mitochondrial encoded cardiolipin synthase converts phosphatidylglycerol into cardiolipin which is incorporated exclusively into the inner mitochondrial membrane. 

Klerman GL, DiMascio A, Weissman MM, et al Treatment of depression by drugs and psychotherapy. Am J Psychiatry 131 186-191, 1984 Kleven MS, Seiden LS D-, L- and DL-fenfluramine cause long-lasting depletions of serotonin in rat brain. Brain Res 505 351-353, 1989 Kligman D, Marshak D Purification and characterization of a neurite extension factor from bovine brain. Proc Natl Acad Sci U S A 82 7136-7139, 1985 Klimek V, Maj J Repeated administration of antidepressants enhances agonist affinity for mesolimbic D2 receptors. J Pharm Pharmacol 41 555-558, 1989 Klinkhamer P, Szelies B, Heiss WD Effect of phosphatidylserine on cerebral glucose metabolism in Alzheimer s disease. Dementia 1 197-201, 1990... 

Fig. 20.3. Schematic representation of the main pathways in the lipid metabolism of parasitic flatworms. Boxed substrates are supplied by the host. Pathways present in mammalian systems but absent in parasitic flatworms are shown by open arrows. Abbreviations DAG, diacylglycerol CDP-DAG, cytidine diphosphodiacylglycerol Farnesyl PP, farnesyl pyrophosphate Geranyl PP, geranylpyrophosphate Geranylgeranyl PP, geranylgeranylpyrophosphate FlMG-CoA, hydroxymethylglutaryl-CoA TAG, triacylglycerol PA, phosphatidic acid PC, phosphatidylcholine PE, phosphatidylethanolamine PI, phosphatidylinositol PS, phosphatidylserine.

Pyridoxal phosphate has a clear role in lipid metabolism as the coenzyme for the decarboxylation of phosphatidylserine, leading to the formation of phosphatidylethanolamine, and then phosphatidylcholine (Section 14.2.1), and membrane lipids from vitamin Bg-deficient animals are low in phosphatidylcholine (She et al., 1995). It also has a role, less well defined, in the metabolism of polyunsaturated fatty acids vitamin Bg deficiency results in reduced activity of A desaturase and impairs the synthesis of eicosapentanoic and docosahexanoic acids (Tsuge et al., 2000). 

Almost all body cells contain phospholipids. The common animal phospholipids are made of sphingomyelin, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and other glycerol phospholipids of complex fatty acid composition. PC, formerly referred to as lecithin, PE, formerly referred to as cephalin, and PS are by far the most predominant phospholipids from most animal sources. As constituents of cell walls and active participants in metabolic processes, they appear to be essential to life (8). 

The simplest topic covered in this chapter is that of choline, a compound with a 2-carbon backbone, which occurs in the diet and in the body mainly in the form of the structural lipid phosphatidylcholine. Choline is an issue in the metabolism of other lipids, namely, of phosphatidylserine, phosphatidylethanola-mine, and sphingomyelin. Phosphatidylino-sitol is a lipid that has received enormous attention from cell biologists because of its role in transmitting signals within the cell. Sphingomyelin is a structmal lipid in the plasma membrane, but it has received increased attention because of its role in regulating the growth, differentiation, and death of cells. 

Myelin is approximately 75% lipid and 25% protein. Carbohydrate residues are associated with both the lipid and the protein components of myelin. High proportions of cholesterol, phospholipid, and glycolipid are found in the lipid fractions. Phospholipids include ethanolamine phosphatides, phosphatidylserine, and phosphatidylinositol glycolipids include both neutral (cerebroside, sulfatide, galactosyldiglyceride) and polar (gangliosides, especially GMj and GMJ lipids. A classification and discussion of the metabolism of brain lipids is beyond the scope of this article readers are referred to Lajtha (1969), Davison (1968), Awasthi and Srivastava (1980), and Suzuki (1981). 

Elabbadi, N., Ancelin, M. L., and Vial, H. J. (1997). Phospholipid metabolism of serine in Plasmodium-infected erythrocytes involves phosphatidylserine and direct serine decarboxylation. Biochem. ]. 324(Pt 2), 435M45. 

Pyruvoyl cofactor is derived from the posttranslational modification of an internal amino acid residue, and it does not equilibrate with exogenous pyruvate. Enzymes that possess this cofactor play an important role in the metabolism of biologically important amines from bacterial and eukaryotic sources. These enzymes include aspartate decarboxylase, arginine decarboxylase," phosphatidylserine decarboxylase, . S-adenosylmethionine decarboxylase, histidine decarboxylase, glycine reductase, and proline reductase. ... 

Phosphatidylinositol is uncommon in bacteria and is found in a few Gram-positive species only. In actinomycetes and a few other bacteria mannosides of phosphatidylinositol may be present. Other glycerophospholipids such as phosphatidic acid and phosphatidylserine have a widespread occurrence in bacteria but only in small amounts. Both of these lipids play an important role as metabolic intermediates (Finnerty, 1978 Raetz, 1978). 

---