Membrane lipids synthesis

This three-step process for transferring fatty acids into the mitochondrion—esterification to CoA, transesterification to carnitine followed by transport, and transesterification back to CoA—links two separate pools of coenzyme A and of fatty acyl-CoA, one in the cytosol, the other in mitochondria These pools have different functions. Coenzyme A in the mitochondrial matrix is largely used in oxidative degradation of pyruvate, fatty acids, and some amino acids, whereas cytosolic coenzyme A is used in the biosynthesis of fatty acids (see Fig. 21-10). Fatty acyl-CoA in the cytosolic pool can be used for membrane lipid synthesis or can be moved into the mitochondrial matrix for oxidation and ATP production. Conversion to the carnitine ester commits the fatty acyl moiety to the oxidative fate. 

Sreenivas, A., Patton-Vogt, J.L., Bruno, V, Griac, P., and Henry, S.A., 1998, A role for phospholipase D (Pldlp) in growth, secretion, and regulation of membrane lipid synthesis in yeast. J. Biol. Chem. 273 16635-16638. 

Membrane-lipid synthesis continues in the endoplasmic reticulum. Phospholipid synthesis requires the combination of a diacyl glycerol with an alcohol. As in most anabolic reactions, one of the components must be activated. In this case, either the diacylglerol or the alcohol may be activated, depending on the source of the reactants. 

Cronan, J.E., Jr. 2003. Bacterial membrane lipids where do we stand Annu. Rev. Microbiol. 57 203-224. Schujman, G.E., de Mendoza, D. 2005. Transcriptional control of membrane lipid synthesis in bacteria. Curr. Opin. Microbiol. 8 149-153. 

The diagram in Figure 1 shows that when 24 6 n-3 is degraded to 4,7,10,13,16,19-22 6, in peroxisomes, it may either be further degraded to 20 5 n-3 by another cycle of fl-oxidation or move out of peroxisomes to the endoplasmic reticulum where it is used for phospholipid synthesis. The removal of a double bond at position-4 in PUFA by peroxisomes is a slow step in the degradative process (reviewed in 51). When 22-carbon acids, with their first double bond at position-4, are produced in peroxisomes, ex vivo studies show that they are preferentially transferred to microsomes where they are used for membrane lipid synthesis rather than continued 3-oxidation (40,41). The diagram in Figure 1 shows that when 22 6n-3 is produced in peroxisomes, it moves back to the endoplasmic reticulum as the acyl-CoA. It is equally likely that the acyl-CoA is hydrolyzed and that 4,7,10,13,16,19-22 6 must be reactivated. 

The changes documented here, as well as others described elsewhere (Bazan et al., 1976), in the drugs action on membrane lipid synthesis in the retina pose the question of whether or not they are related to the normal functioning of the central nervous system. The test of such a possibility was carried out by applying to the entire retina its natural stimulus and comparing it with retinas kept in darkness. 

In plants, de novo fatty acid biosynthesis occurs exclusively in the stroma of plastids, whereas, with the exception of plastidial desaturation, modification of fatty acid residues including further desaturation and triacylglrycerol (TAG) assembly are localized in the cytosol/endoplasmic reticulum (ER). The primary fatty acids formed in the plastid (palmitic, stearic, and oleic acid) are used in the plastidic prokaryotic pathway for membrane lipid synthesis or diverted to the cytoplasmic eukaryotic pathway for the synthesis of membrane lipids or storage TAGs (1). Movement of glycerolipids is believed to occur in the reverse direction between the cytosol/ER and the plastids in the highly regulated manner (2). 

Arabidopsis is a typical 16 3-plant in which both the prokaryotic and eukaryotic pathways [4] contribute to the production of chloroplast lipids. We have investigated the pattern of lipid metabolism in wild type Arabidopsis and calculated the fluxes of carbon involved [5]. An abbreviated version of this analysis is shown in Fig. la. For every 1000 fatty acid molecules synthesized in the chloroplast 390 enter the prokaryotic pathway in the chloroplast envelope while 610 are exported as CoA esters to enter the eukaryotic pathway. Of these 340 are reimported into the chloroplast. Overall, almost equal amounts of chloroplast lipids are produced by each pathway. However, the quantities of individual lipids synthesized by the two routes are very different. All the chloroplast phosphatidylglycerol (PG) and over 70% of the monogalactosyldiacylglycerol (MGD) is derived from the prokaryotic pathway while digalactosyldiacylglycerol is synthesized mainly on the eukaryotic pathway [5]. In this paper we have outlined how four of the Arabidopsis mutants have changed the way we view the operation of the two pathways involved in leaf membrane lipid synthesis. More detailed information on each mutant can be found elsewhere [1-3, 5,6 and in preparation]. 

In spite of a relatively concerted effort recently directed to the study of plant lipid metabolism, many important and interesting questions remain unanswered. For a variety of reasons, plants often seem more intransigent than animals in yielding up their secrets. Our laboratory has initiated a study of membrane lipid synthesis and turnover in a simple eukaryotic green alga, Dunaliella salina, hoping that the ease of experimentation with it will lead to new and widely applicable knowledge. 

In conclusion, although the main site of storage and membrane lipid synthesis in Brassica napus is the E.R., TAG is also synthesised by light vesicles, the nature of which have yet to be fully elucidated. 

The insulin receptor is a transmembrane receptor tyrosine kinase located in the plasma membrane of insulin-sensitive cells (e.g., adipocytes, myocytes, hepatocytes). It mediates the effect of insulin on specific cellular responses (e.g., glucose transport, glycogen synthesis, lipid synthesis, protein synthesis). 

Cyanobacteria, prokaryotic algae that perform oxygenic photosynthesis, respond to a decrease in ambient growth temperature by desaturating the fatty acids of membrane lipids to compensate for the decrease in the molecular motion of the membrane lipids at low temperatures. During low-temperature acclimation of cyanobacterial cells, the desaturation of fatty acids occurs without de novo synthesis of fatty acids [110, 111]. All known cyanobacterial desaturases are intrinsic membrane proteins that act on acyl-Hpid substrates. 

Mercury is known to exert an effect on the synthesis of membrane lipids. Mercuric chloride produces lipid alteration in pig kidney epithelial cells (LLC-PK, cells), with rapid accumulation of unesterified fatty acids (particularly arachidonic acid) and lysophospholipids and loss of cellular phospholipids... 

The levels of PAF synthesis and release are also modulated by levels of extracellular albumin. In the absence of albumin, neutrophils (stimulated with fMet-Leu-Phe) synthesise only low levels of PAF within 1-2 min of stimulation. In the presence of 0.25% albumin, PAF synthesis is increased, and up to half of this may be released with 5% albumin, rates of synthesis and release are increased further and sustained over a 30-min period. Newly-synthesised PAF is reincorporated by neutrophils into membrane lipids and is therefore poorly soluble in aqueous media. Thus, extracellularly added albumin will bind to cell-associated PAF and effectively solubilise it at concentrations below its critical micellar concentration (CMC). This will effectively enhance the PAF release rate, which will decrease the concentration of cell-associated PAF thus, the rate of biosynthesis will be sustained. 

In mammalian cells, the final stage of PS biosynthesis occurs in ER and MAM (Trotter and Voelker, 1994 Daum and Vance, 1997 Voelker, 2000). The other membranes in the ceU, such as mitochondria, nucleus, and plasma membrane, are therefore assembled from PS exported from ER and MAM (Figure 2). Phospholipid synthesis in mitochondria is restricted to the formation ofphosphatidylglycerol, cardiolipin, and PE, and other lipids such as PC and PS must be imported from sites of cellular lipid synthesis, ER or MAM (Daum, 1985 Vance, 1991). PS imported to the outer mitochondrial membrane is then translocated to the inner mitochondrial membrane, where it is converted to PE by PS decarboxylase (PSD) (Dennis and Kennedy, 1972 Voelker, 1990). It has been shown that the translocation of PS to mitochondria followed by its decarboxylation is a major pathway for the synthesis of PE in some cultured mammahan cells (Voelker, 1984 Kuge et al, 1986 Voelker and Frazier, 1986), suggesting that significant amounts of PE found in cell membranes are derived from mitochondria. 

Rusinol, A.E., Cui, Z, Chen, M.H., and Vance, J.E., 1994, A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins. J. Biol. Chem., 269 27494-27502. 

Membrane-located enzymes in the sER catalyze lipid synthesis. Phospholipid synthesis (see p. 170) is located in the sER, for example, and several steps in cholesterol biosynthesis (see p. 172) also take place there. In endocrine cells that form steroid hormones, a large proportion of the reaction steps involved also take place in the sER (see p. 376). 

Mechanism of Action A topical agent that binds DNA, inhibiting synthesis of nucleic protein, and reduces mitotic activity. Therapeutic Effect Results in damage to DNA sugar and enhances membrane lipid peroxidation, which may play a critical role in the antipsoriatic action. 

Ester synthesis of cholesterol linoleate. Cholesterol fatty acid ester is an important cell membrane lipids and has many applications in cosmetics, pharmaceutical and other industries. Akehoshi et aL(7) reported the ester synthesis of the cholesterol fatty acid ester with native lipase. Synthesis of the cholesterol fatty acid ester was also carried out in water-saturated n-hexane by palmitic acid-modified lipase. As shown in Table III, this system made it possible for the synthesis of the cholesterol fatty acid ester in organic solvents using the modified lipase. 

In this chapter we first describe the composition of cellular membranes and their chemical architecture— the molecular structures that underlie their biological functions. Next, we consider the remarkable dynamic features of membranes, in which lipids and proteins move relative to each other. Cell adhesion, endocytosis, and the membrane fusion accompanying neurotransmitter secretion illustrate the dynamic role of membrane proteins. We then turn to the protein-mediated passage of solutes across membranes via transporters and ion channels. In later chapters we discuss the role of membranes in signal transduction (Chapters 12 and 23), energy transduction (Chapter 19), lipid synthesis (Chapter 21), and protein synthesis (Chapter 27). 

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