Plasmalogen synthesis

Reactions described in this chapter that are catalyzed by mixed-function oxidases are those involved in fatty acyl-CoA desaturation (Fig. 21-13), leukotri-ene synthesis (Fig. 21-16), plasmalogen synthesis (Fig. 21-30), conversion of squalene to cholesterol (Fig. 21-37), and steroid hormone synthesis (Fig. 21-47). 

Plasmalogen Synthesis Requires Formation of an Ether-Linked Fatty Alcohol... 

Although the mitochondria are the primary site of oxidation for dietary and storage fats, the peroxisomal oxidation pathway is responsible for the oxidation of very long-chain fatty acids, jS-methyl branched fatty acids, and bile acid precursors. The peroxisomal pathway also plays a role in the oxidation of dicarboxylic acids. In addition, it plays a role in isoprenoid biosynthesis and amino acid metabolism. Peroxisomes are also involved in bile acid biosynthesis, a part of plasmalogen synthesis and glyoxylate transamination. Furthermore, the literature indicates that peroxisomes participate in cholesterol biosynthesis, hydrogen peroxide-based cellular respiration, purine, fatty acid, long-chain... 

Prisianic acid y -oxidation Plasmalogen level DHAPAT/alkylDHAP synthase De novo plasmalogen synthesis... 

Carr, H. G., H. Haerle, and J. J. Eiler Phospholipid and plasmalogen synthesis in rat-brain homogenates. Biochim. biophys. Acta (Amst.) 70, 205—7 (1963). 

The results of Fig,6 are of particular interest, since they might suggest the existence of a new and important pathway for choline plasmalogen synthesis in brain. The mechanisms for the formation of this lipid in brain are in fact stiU unknown, in contrast to v4iat is known about ethanolamine plasmalogen synthesis. 

Another type of lipid, the ether-linked phospholipids (e.g., plasmalogens), comprises about 20% of membrane phospholipids (Figure 7). Plasmalogen synthesis requires enzymes present in both peroxisomes and the endoplasmic reticulum. These lipids are thought to be part of the cellular defense mechanism against oxidative injury. 

Figure 24-4. Biosynthesis of ether lipids, including plasmalogens, and platelet-activating factor (PAF). In the de novo pathway for PAF synthesis, acetyl-CoA is incorporated at stage, avoiding the last two steps in the pathway shown here.

Synthesis of plasmalogens involves formation of their characteristic double bond by a mixed-function oxidase. The head groups of sphingolipids are attached by unique mechanisms. 

Apparently the synthesis via serine and phosphatidylserine cannot provide an adequate amount of choline, which is present in the body not only in phosphatidylcholine but in plasmalogens, sphingomyelins, and the neurotransmitter acetylcholine.185... 

Also, the primary amine moities of polar lipids catalyze the aldol condensation of Cm-Cig aldehydes resulting from plasmalogen hydrolysis, thus forming a,3-unsaturated aldehydes (l2t). Phosphatidyl ethanolamine reacted with propanal and n-hexanal forming phosphatidyl l-(2-hydroxyethyl)-2-ethyl-3,5-dimethyl pyridinium, and phosphatidyl-1-(2-hydroxy ethyl)-2-hexyl-3,5-dipentyl pyridinium, respectively (125). The peridinium ring is formed by the reaction between one mole of amino-N of phosphatidyl ethanolamine and three moles of n-alkanals. The same reaction took place in the synthesis of substituted pyridines by condensation of carbonyl compounds with ammonia (126, 127). 

Cymerman-Craig, J. and Hamon, D. P. G. (1965) Studies directed toward the synthesis of plasmalogens II ( ) cis- and rran.v-3/n-hexadec-l -enyloxyl-1,2-propanediol, J. Org. Chem. 30, 4168-4175. 

Cholesterol and phospholipids. Most lipids found in myelin are common to other cellular membranes. Cholesterol content is high and cholesterol esters are not present in normal myelin. Phospholipids are also common to other cellular membranes, except for the great quantity of ethanolamine phosphoglycerides in the plasmalogen form. The synthesis of plasmalogens is modified in Zellweger syndrome which is a peroxisomal syndrome that also increases VLCFA. This syndrome and other peroxisomal diseases may cause demyelination (Powers, 2005). 

The desaturase catalyzing this final step in the synthesis of a plasmalogen is an endoplasmic reticulum enzyme akin to the one that introduces double bonds into long-chain fatty acyl CoA molecules. In both cases, O2 and NADH are reactants, and cytochrome b 5 participates in catalysis (Section 22.6). 

The reagent is useful for the synthesis of a-glycerylphosphorylethanolamine (4), a moiety of cephalin and plasmalogens. D-Acetone glycerol (1) is phosphorylated... 

Peroxisomes contain dihydroxyacetone phosphate acyl-transferase and alkyldihydroxyacetone phosphate synthase, which are involved in synthesis of the plasmalogens (Chapter 19). Peroxisomes may also participate in the biosynthesis of bile acids. The conversion of trihydrox-ycholestanoic acid to cholic acid (Chapter 19) has been localized to peroxisomes. 

Nieto, M. L., Venable, M. E Bauldry, S. A., Greene, D. G., Kennedy, M., Bass, D. A., Wykle, R. L. (1991). Evidence that hydrolysis of ethanolamine plasmalogens triggers synthesis of plateletactivating factor via a transacylation reaction. J. Biol. Chem. 266, 18699-18706. 

The final steps in the synthesis of glycerophosphollplds, plasmalogens, and sphingolipids are catalyzed by membrane-... 

As already noted, the final steps In the synthesis of cholesterol and phospholipids take place primarily In the ER, although some of these membrane lipids are produced In mitochondria and peroxisomes (plasmalogens). Thus the plasma membrane and the membranes bounding other organelles (e.g., Golgi, lysosomes) must obtain these lipids by means of one or more Intracellular transport processes. For example. In one Important pathway, phosphatidylserine made In the ER Is transported to the Inner mitochondrial membrane where It Is decarboxylated to phosphatidylethanolamlne, some of which either returns to the ER for conversion Into phosphatidylcholine or moves to other organelles. 

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