Lecithin, biosynthesis

Which reaction in the following set is rate controlling in lecithin biosynthesis ... 

Lecithin is the most abundant membrane phospholipid in our cells. A study involving cells with a temperature-sensitive genetic defect in lecithin biosynthesis illustrates how essential it is for cell survival. When grown above a certain temperature, these cells were unable to... 

Four enzymes, required for the lecithin biosynthesis are reconstituted in a soybeanPC proteoliposome. Short- and long-chain lecithin can be synthesized within such liposomes, that were prepared by the detergent depletion method. 

Since rather high fungicide concentrations were used in this study, it is not clear whether the observed effects are a reaction to general cell death rather than a specific inhibition of lecithin biosynthesis. In conclusion, considering all observations published so far, the biochemical mode of action of CAA fungicides is still not elucidated. 

Transfer of a phosphocholine residue to the free OH group gives rise to phosphatidylcholine (lecithin enzyme l-alkyl-2-acetyl-glycerolcholine phosphotransferase 2.7.8.16). The phosphocholine residue is derived from the precursor CDP-choline (see p. 110). Phos-phatidylethanolamine is similarly formed from CDP-ethanolamine and DAG. By contrast, phosphatidylserine is derived from phosphatidylethanolamine by an exchange of the amino alcohol. Further reactions serve to interconvert the phospholipids—e.g., phosphatidylserine can be converted into phosphatidylethanolamine by decarboxylation, and the latter can then be converted into phosphatidylcholine by methylation with S-adenosyl methionine (not shown see also p. 409). The biosynthesis of phosphatidylino-sitol starts from phosphatidate rather than DAG. 

Lecithins and related phospholipids usually contain a saturated fatty acid in the C-l position but an unsaturated acid, which may contain from one to four double bonds, at C-2. Arachidonic acid is often present here. Hydrolysis of the ester linkage at C-2 yields a l-acyl-3-phosphoglycerol, better known as a Iysophosphatidylcholine. The name comes from the powerful detergent action of these substances which leads to lysis of cells. Some snake venoms contain phospholipases that form Iysophosphatidylcholine. Lysophosphatidic acid (l-acyl-glycerol-3-phosphate) is both an intermediate in phospholipid biosynthesis (Chapter 21) and also a signaling molecule released into the bloodstream by activated platelets.15... 

Bjerve, K.S. (1973). The Ca2+-dependent biosynthesis of lecithin, phosphatidylethanolamine and phosphatidylserine in rat liver subcellular particles. Biochim. Biophys. Acta 296,549-562. Bloch, F., Hansen, W.W., Packard, M. (1946). Nuclear induction. Phys. Rev. 69,127. Borkenhagen, L.F., Kennedy, E.P., Fielding, L. (1961). Enzymatic formation and decarboxylation of phosphatidylserine. J. Biol. Chem. 236, PC28-PC30. 

Choiine. Choline is a component of many biomem-hranes and plasma phospholipids. Dietary sources include eggs. fish, liver, milk, and vegetables. These sources provide choline primarily as the phospholipid lecithin. Lecithin is hydrolyzed to glycerophosphorylcholinc by the intestinal mucosa before absorption. The liver liberates choline. Choline can be biosynthesized by humans con.sequcntly. it cannot be con.sidcred a (rue vitamin. Biosynthesis involves methylation of cthanolamine. The methyl groups arc provided by methionine or by a reaction involving vitamin B12 and folic acid. Therefore, deficiencies can occur only if all methyl donors are excluded from the diet. 

P13. Pennington, R. J., and Worsfold, M., Biosynthesis of lecithin by skeletal muscle. Biochim. Biophys. Acta 176, 774-782 (1969). 

The biosynthesis of sphingosine and the formation of ceramides have already been discussed. The last step in the biosynthesis of sphingomyelins (see Fig. 3-39) involves cytidine diphosphate choline as a phosphate donor, in a reaction similar to that involved in the biosynthesis of lecithin. Scribney and Kennedy have found a chicken liver enzyme, now called the PC ceramide transferase, which catalyzes the following reaction ... 

The 1, 2-diglyceride arises by a dephosphorylation of a diacyl-phospha-tidic acid (a glycerophosphatide without the base) in the presence of a specific phosphatase. The phosphatidic acids which are intermediates in the biosynthesis of lecithins are the result of a combination, in the presence of ATP and a specific enzyme, of a-glycerophosphoric acid with two molecules of fatty add activated by CoA. These compounds of aliphatic acids and CoA are provided by the fatty acid cycle functioning in the direction of biosynthesis. The enzyme catalysing acyl transfer has a special spedfidty for the acyl-CoA derivatives of the Cu and Cjg acids. 

A major advance in the understanding of the biosynthesis of the glycerophos-phatides was the discovery by Kennedy and Weiss (1956) of the role of nucleotides of cytosine in the biosynthesis of the glycerophosphatides. Cytidine 5 -triphosphate (CTP) was shown to be necessary for the incorporation of phosphorylcholine into lecithin by liver preparations. Similar observations have been reported for brain (McMubbay et al. 1957, Stbickland et al. 1963) and other tissues. The nucleotide requirement is specific for CTP, none of the other nucleoside 5 -triphosphates being active. Kennedy and Weiss (1956) showed that CTP combines with phosphorylcholine to form the intermediate CDP-choline (IV) according to the equation ... 

The enzymes leading to the biosynthesis of lecithin by the pathways outlined above (Reactions 11 and 12) are not restricted to liver. They have been demonstrated in brain (Strickland et al. 1963) seminal vesicle (Williams-Ashman and Banks 1956) and intestinal mucosa (Gurr and Hubscher 1964). Experiments such as those of Miani and Bucciante (1958), in which inorganic P was administered to rats, and those of G0RANSSON (1964), in which labelled fatty acids were given, provided evidence that this pathway for the biosynthesis of lecithin is operative in vivo. 

Many of the reactions leading to the biosynthesis of lecithin are summarized in Figure 2. The sequences shown in the flgure do not represent all of the possibilities however. For example, Lands and Mebkl (1963) have shown that in liver preparations lecithin may be formed as the result of the acylation of lyso-lecithin (VI) by acyl CoA ... 

The plasmalogenic diglyceride, prepared enzymically by the action of phospholipase C on the choline-containing phospholipid of beef heart, is defined as a D-a,/5-diglyceride in which the ester at the cx -position is replaced by an imsaturated ether. The reaction is catalysed by a choline-phosphotransferase enzyme similar to the phosphorylcholine-glyceride transferase shown to participate in the biosynthesis of lecithin (Reaction 12). A similar reaction occurs in brain (McMurray 1964b). 

As stressed for the biosynthesis of lecithin, the possibility of alternative pathways should be borne in mind. An example is the demonstration by Mebkl and Lands (1963) of the enzymic acylation of lysophosphatidyl ethanolamine to form phosphatidyl ethanolamine by a reaction similar to that described for the acylation of lysolecitW to form lecithin (Reaction 16). 

Bremer, J., and D. M. Greenberg Methyl transfering enzyme system of microsomes in the biosynthesis of lecithin (phosphatidylcholine). BiocMm. biophys. Acta (Amst.) 46, 205—16 (1961). 

D. SuBRAHMANYAM, E. T. Pritchard, W. THOMPSON, and R. J. Rossiter Biosynthesis of lecithin in brain. Participation of cytidine diphosphate choline and phosphati c acid. Biochem. J. 87, 128—36 (1963). 

Sphingomyelin. Weiss and Kennedy (1956) have described the synthesis of lecithin from CDP-choline and a diglyceride. An analogous reaction was reported by Sribney and Kennedy (1958) to be involved in the biosynthesis of sphingomyelin. This reaction is formulated below ... 

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