Serine ethanolamine from

The major phosphoglycerides are derived from phosphatidate by the formation of an ester bond between the phosphate group of phosphatidate and the hydroxyl group of one of several alcohols. The common alcohol moieties of phosphoglycerides are the amino acid serine, ethanolamine, choline, glycerol, and the inositol. 

CDP-diacylglycerol is made by eombining phosphatidic acid and CTP (Figure 19.3). In eaeh of the glyeerophospholipid reaetion pathways from CDP-diacylglycerol, CMP is split from the moleeule in order to put on the serine, ethanolamine, glycerol, or inositol moieties. 

Formation of ethanolamine from betaine and of choline from ethanolamine was also shown by the experiments of Stetten. The data are reproduced in Table I. The observations support the main features of the cycle represented in Fig. 1, namely that ethanolamine is formed by the decarboxylation of serine, this in turn is methylated to choline, which is then oxidized to betaine, and the latter is demethylated to glycine. Further support for this scheme is supplied by the observations of Arn-stein that L-serine-S-C is converted to choline with about the same degree of efficiency as N -glycine and that glycine-l-C is not a precursor of choline. 

The aldehydes, which have been isolated from these plasmalogens, are predominantly saturated and monounsaturated aldehydes (16 0, 18 0, 18 1, 18 1 ). In contrast, the fatty acids linked to the /9-C-atom in choline plasmalogens are mostly Cig-unsaturated fatty acids, no C22-polyenoic acids have been observed (Klenk et al. 1957 Debuch 1956). Heart muscle mainly contains choline plasmalogens, whereas brain tissue has ethanolamine and serine plasmalogens (Klenk et al. 1951 Ansell et al. 1956). These are localized in brain white matter (Webster 1960). Previous attempts to separate diacylglycerophosphoryl choline or -ethanolamine from the respective plasmalogens were unsuccessful. 

The work of Hubscher (1962) and Borkenhagen, Kennedy and Fielding (1961) indicates that in mammalian tissues phosphatidyl serine (IX) is not formed by the transfer of (9-phosphoserine from CDP-serine to D-cx,j8-diglyceride by a reaction analogous to those already described for the formation of lecithin and phosphatidyl ethanolamine (Reactions 12 and 19). Apparently free serine and not 0-phosphoserine is the immediate precursor of phosphatidyl serine. Serine displaces ethanolamine from phosphatidyl ethanolamine in an enzymic reaction activated by Ca and not requiring ATP ... 

Hydroxypyruvate can be formed from serine by transamination dihy-droxyacetone is readily phosphorylated to triose phosphate. As CO is removed, more hydroxypyruvate could be formed from serine. Some such cycle would provide a nonfolic-mediated disposition of formaldehyde. Formaldehyde, in turn, could be generated by the oxidation of the W-methyl of sarcosine sarcosine in turn is generated by the removal as active formaldehyde of one of the methyls of dimethylglycine (Mackenzie and Frisell, 1968). Dimethylglycine is formed by the well-established sequence sarcosine — glycine + HCHO serine ethanolamine + COj — mono-methylethanolamine —> dimethylethanolamine —> choline —> betaine —> dimethylglycine. 

Identification of diseased states by P NMR originates from the observation of Burt et al. (1976) that intact dystrophic chicken muscle contains an extra resonance not present in normal chicken muscle. The compound giving rise to this signal has been isolated and identified as a phosphodiester, L-serine ethanolamine phosphate (Chalovich et al., 1977). At the same time, it was found that intact normal human leg muscle contains another phosphodiester, 5/i-glycerol 3-phosphorylcholine (GPC), and that this compound is missing in diseased human muscles, notably in Duchenne muscular dystrophy (Barany era/., 1977 Chalovich era/., 1979). This su ested that GPC may be used as a marker for human muscle diseases. 

Phosphatidylethanolamine (cephalin) and ph os-phatidylserine (found in most tissues) differ from phosphatidylcholine only in that ethanolamine or serine, respectively, replaces choline (Figure 14-8). 

Figure 1. Synthetic pathway for PS and PE in mammalian cells. The major steps occuring in the synthesis and interconversion of PS and PE are shown. The PS synthases condense serine with a phosphatidyl moiety derived from PC and PE. The nascent PS can be converted to PE by decarboxylation. PE can also be formed by transfer of a phosphoethanolamine moiety from CDP-ethanolamine to diacylglycerol via the Kennedy pathway. The abbreviations used are PC, phosphatidylcholine PS, phosphatidylserine PE, phosphatidylethanolamine DG, diacylglycerol PSD, phosphatidylserine decarboxylase PSS, PS synthase.

The other phospholipids can be derived from phosphatidates (residue = phosphatidyl). Their phosphate residues are esterified with the hydroxyl group of an amino alcohol choline, ethanolamine, or serine) or with the cyclohexane derivative myo-inositol. Phosphatidylcholine is shown here as an example of this type of compound. When two phosphatidyl residues are linked with one glycerol, the result is cardiolipin (not shown), a phospholipid that is characteristic of the inner mitochondrial membrane. Lysophospholipids arise from phospholipids by enzymatic cleavage of an acyl residue. The hemolytic effect of bee and snake venoms is due in part to this reaction. 

Figure 3.2 The molecular arrangement of the cell membrane (A) integral proteins (B) glycoprotein (C) pore formed from integral protein (D) various phospholipids with saturated fatty acid chains (E) phospholipids with unsaturated fatty acid chains (F) network proteins (G) cholesterol (H) glycolipid (I) peripheral protein. There are four different phospholipids phosphatidyl serine phosphatidyl choline phosphatidyl ethanolamine and sphingomyelin represented as , o. The stippled area of the protein represents the hydrophobic portion. Source From Ref. 1.

With the establishment of the phosphoryl enzyme, the question was whether or not the phosphoryl enzyme was the same as the phospho-protein found by incubating inorganic phosphate with alkaline phosphatase at low pH (35, 114-116, 119, 120). Wilson and Dayan (105) pointed out that the phosphoprotein is thermodynamically very stable It is 105 times more stable than O-phosphorylserine (125) and 0-phosphoryl ethanolamine (105, 126). Alkaline phosphatase, as a true catalyst, must catalyze both the hydrolysis and the formation of phosphate esters. Therefore, if a serine residue existed which was capable of forming a thermodynamically stable phosphate ester, alkaline phosphatase as a nonspecific catalyst would catalyze its formation from both inorganic phosphate and phosphoester substrates. 

Synthesis of most phospholipids starts from glycerol-3-phosphate, which is formed in one step from the central metabolic pathways, and acyl-CoA, which arises in one step from activation of a fatty acid. In two acylation steps the key compound phosphatidic acid is formed. This can be converted to many other lipid compounds as well as CDP-diacylglycerol, which is a key branchpoint intermediate that can be converted to other lipids. Distinct routes to phosphatidylethanolamine and phosphatidylcholine are found in prokaryotes and eukaryotes. The pathway found in eukaryotes starts with transport across the plasma membrane of ethanolamine and/or choline. The modified derivatives of these compounds are directly condensed with diacylglycerol to form the corresponding membrane lipids. Modification of the head-groups or tail-groups on preformed lipids is a common reaction. For example, the ethanolamine of the head-group in phosphatidylethanolamine can be replaced in one step by serine or modified in 3 steps to choline. 

In prokaryotes, phosphatidylserine is made from CDP-diacylglycerol (see fig. 19.3). The enzyme for this reaction is absent in animal cells, which rely on a base exchange reaction in which serine and ethanolamine are interchanged (fig. 19.8). Although the reaction is reversible, it usually proceeds in the direction of phosphatidylserine synthesis. Phosphatidylserine can be converted back to phos-phatidylethanolamine by a decarboxylation reaction in the mitochondria. This may be the preferred route for phosphatidylethanolamine biosynthesis in some animal cells. Furthermore these two reactions (see fig. 19.8) establish a cycle that has the net effect of converting serine into ethanolamine. This is the main route for ethanolamine synthesis... 

Phosphatidylserine biosynthesis in animals is catalyzed by a base exchange enzyme on the endoplasmic reticulum. Decarboxylation of phosphatidylserine occurs in mitochondria. The cyclic process of phosphatidylserine formation from phosphatidylethanolamine and the reformation of phosphatidylethanolamine by decarboxylation has the net effect of converting serine to ethanolamine. This is a major mechanism for the synthesis of ethanolamine in many eukaryotes. 

Studies by Johnston and Roots (1964), Roots (1968) and Kreps (1981) have revealed an increased ratio between the plasmalogenic and diacyl forms of phosphatidyl ethanolamine in oceanic fish from low-temperature waters. During cold adaptation, the ratios between the main phospholipid fractions alter the relative proportion of phosphatidyl choline decrease and phosphatidyl ethanolamine, phosphatidyl serine and sphingomyelin, all of which contain large amounts of polyenoic acids, increase (Caldwell and Vemberg, 1970 Miller etal, 1976 Wodke, 1978 Hazel, 1979 Brichon et al., 1980 van den Thillart and de Bruin, 1981 Zabelinsky and Shukolyukova, 1989). 

Cephalins are glycerophospholipids present in foods. They differ from lecithins by having ethanolamine or serine instead of choline in their structure. Could you differentiate between lecithins and cephalins on the basis of the three tests to be performed in this experiment ... 

Folch, J. (1942) Brain cephalin, a mixture of phosphatides. Separation from it of phosphatidyl serine, phosphatidyl ethanolamine and a fraction containing an inositol phosphatide, J. Biol. Chem. 146, 35-44. 

Figure 11-3. The model of rhodopsin oligomer. View from cytoplasmic side while cytoplasmic loops of rhodopsin molecules were removed. A single dimer is marked by ellipse. Positions of phospholipids are indicated by balls. PEDS - phospholipids with ethanolamine heads, PSDS - with serine heads...

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. 

In mammals, phosphatidyl ethanolamine can be formed from phosphatidyl serine by the enzyme-catalyzed exchange of ethanolamine for the serine moiety of the phospholipid. 

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