Phosphatidylcholine regulation

The regulation of triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine biosynthesis is driven by the availability of free fatty acids. Those that escape oxidation are preferentiaUy converted to phos-phohpids, and when this requirement is satisfied they are used for triacylglycerol synthesis. 

Tijburg LBM, Geelen MJH, van Golde LMG Regulation of the biosynthesis of triacylglycerol, phosphatidylcholine and phos-phatidylethanolamine in the liver. Biochim Biophys Acta 1989 1004 1. 

Therefore, it is currently believed that anandamide is formed from membrane phospholipids (Fig. 4) through a pathway that involves (1) a trans-acylation of the amino group of phosphatidylethanolamine with arachidonate from the sn-1 position of phosphatidylcholine and (2) a D-type phosphodiesterase activity on the resulting A-arachidonylphosphati-dylethanolamide (NAPE). Synthesis of anandamide is presumably regulated at the levels of both enzymes, the A-acyltranferase and the phospholipase D, by stimuli that raise intracellular calcium or by receptors linked with cAMP and PKA. It has been shown that anandamide is formed when neurons are depolarized and, therefore, the intracellular calcium ion levels are elevated (Cadas, 1996). 

Luberto, C., and Hannun, Y. A., 1998, Sphingomyelin synthase, a potential regulator of intracellular levels of ceramide and diacylglycerol during SV40 transformation. Does sphingomyelin synthase account for the putative phosphatidylcholine-specific phospholipaseC /. Biol. Chem. 273 14550-14559. 

MacNulty EE, McClue SJ, Carr IC, Jess T, Wakelam MJ, Milligan G (1992) a2-C10 adrenergic receptors expressed in rat 1 fibroblasts can regulate both adenylylcy-clase and phospholipase D-mediated hydrolysis of phosphatidylcholine by interacting with pertussis toxin-sensitive guanine nucleotide-binding proteins. J Biol Chem 267 2149-2156... 

Additional regulation of phosphatidylcholine and phosphatidylethanolamine biosynthesis occurs at the second step in the biosynthetic sequence (see fig. 19.4) where either CDP-choline or CDP-ethanolamine are made. For phosphatidylcholine biosynthesis, the activity of CTP phos-phocholine cytidylyltransferase (which makes CDP-choline) is governed by an unusual mechanism. The enzyme... 

In some cases the functions of phospholipases in cells are purely degradative and result in the release of the phospholipid components (fatty acids, glycerol, phosphate, and head-groups). But in many cases phospholipases have important roles in synthesis and regulation. For example, we have seen how phospholipase A2 catalyzes the first step in the remodeling of phosphatidylcholine to the surfactant... 

Phosphatidylcholine biosynthesis appears to be regulated principally at the step catalyzed by CTP phos-phocholine cytidylyltransferase. Does the type of regulation observed make biochemical sense Draw a chemical reaction mechanism for this enzyme. 

Li Y., Maher P., and Schubert D. (1998). Phosphatidylcholine-specific phospholipase C regulates glutamate-induced nerve cell death. Proc. Natl. Acad. Sci. USA 95 7748-7753. 

Physically, the membrane may exist in two states the "solid" gel crystalline and the "liquid" fluid crystalline states. For each type of membrane, there is a specific temperature at which one changes into the other. This is the transition temperature (Tc). The Tc is relatively high for membranes containing saturated fatty acids and low for those with unsaturated fatty acids. Thus, bilayers of phosphatidylcholine with two palmitate residues have a Tc = 41°C but that with two oleic acid residues has a Tc = -20°C. The hybrid has a Tc = -5°C. Sphingomyelin bilayer, on the other hand, may have a Tc of close to body temperature. In the gel crystalline state, the hydrophobic tails of phospholipids are ordered, whereas in the fluid crystalline state they are disordered. At body temperature, all eukaryotic membranes appear to be in the liquid crystalline state, and this is caused, in part, by the presence of unsaturated fatty acids and in part by cholesterol. The latter maintains the fatty acid side chains in the disordered state, even below the normal Tc. There is thus no evidence that membranes regulate cellular metabolic activity by changing their physical status from the gel to the fluid state,... 

Phosphatidylcholine is preferentially synthesized in lactating mammary tissue (Kinsella, 1973), possibly regulated by the differential activities of choline kinase and ethanolamine kinase. Choline kinase has a lower Km and a higher Vmax with its substrate than does ethanolamine kinase. Also, choline kinase is inhibited slightly by ethanolamine, whereas choline is a potent competitive inhibitor of ethanolamine kinase. Thus, the intracellular concentration of choline probably regulates the synthesis of these two phos-phoglycerides (Infante and Kinsella, 1976). 

Griac, P., and Henry, S.A., 1996, Phosphatidylcholine biosynthesis in Saccharomyces cerevisiae Effects on regulation of phospholipid synthesis and respiratory competence. In Op den Kamp, J.A.F. (ed.), NATO ASI Series Molecular Dynamics of Biological Membranes. Springer, Verlag, pp. 339-346. 

Patton-Vogt, J.L., Griac, P., Sreenivas, A., Bruno, V, Dowd, S., Swede, M.J., and Henry, S.A., 1997, Role of the yeast phosphatidylinositol/phosphatidylcholine transfer protein (Secl4p) in phosphatidylcholine turnover and INOl regulation. J. Biol. Chem. 272 20873-20883. 

Scherer, G.F.E., Paul, R.U., Hoik, A. and Marinec, J., 2002, Down-regulation by elicitors of phosphatidylcholine-hydrolyzing phospholipase C and up-regulation of phospholipase A2 in plant cells. Biochem. Biophys. Res. Comm. 293 766-770. 

Choline is an essential component of phospholipids - phosphatidylcholine (lecithin) is the major phospholipid in cell membranes and sphingomyelin is important in the nervous system. Acetylcholine is a transmitter in the central and parasympathetic nervous systems and at neuromuscular junctions, and has a role in the regulation of differentiation and development of the nervous system (Biagioni et al., 2000). Acetylcholine is also synthesized in mononuclear lymphocytes, where it has an autocrine or paracrine role in regulating immune function (Fujii and Kawashima, 2001). 

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