Membranes lipids in cell

A number of workers have observed amino acids in lipide extracts, including those of microbial origin (11, 12, 17, 29). Recently, Macfar-lane (34) has reported that most of the phospholipide in Clostridium welchii is bound to amino acids and that some of this material occurs as the O-amino acid ester of phosphatidylglycerol. The relatively prominent occurrence of lipides in cell membranes has led to the recurrent suggestion that transport of hydrophilic substances through such membranes would be greatly facilitated by combination with hydrophobic substances. Consequently, most workers who have observed the incorporation of amino acids into lipide fractions quite naturally... 

Vitamin E, (tocopherols) C29H50O2 (Figure 6.8), which acts as an anti-oxidant to prevent the free radical oxidation of lipids in cell membranes. There are sufficient supplies of vitamin E in vegetable oils. 

Ptdlns is the most abundant phosphatidylinositide in cells it constitutes about 90% of the inositol lipids in cell membranes. The other six mono- and bis-phosphorylated Ptdlns make up the remaining 10% with PtdIns(4)Pj and PtdIns(4,5)P2 constituting up about 9% of the lipid pool, each contributing different amounts depending on the tissue. The remaining five lipids make up 1%. PtdIns(3)Pi or PtdIns(5)Pi contribute about 0.4%, and the 3-lipids jointly constitute about 0.1%. These numbers vary slightly from cell to cell (Stephens et al., 2000 Vanhaesebroek et al., 2001), however, it is clear that the quantitatively minor inositol lipids Ptd(4,5)P2 and the 3-phosphorylated lipids play critical roles in signal transduction (Stephens et al., 2000 Toker and Cantley, 1997 Vanhaesebroek et al., 2001). 

PhosphattdykhoHne (PC) and phosphatidylethanolamine (PE) are the major phospholipids of cell membranes. Table 6.1 lists the amount of lipid in cell membranes expressed as micrograms of lipid per milligram of membrane-bound protein. The membranes were isolated from cells of adipose tissue from rats that had been raised on a diet containing sunflower oil (100 g oil/kg diet) as the source of lipids. The diet was essentially free of cholesterol and phospholipids because plants do not contain cholesterol and the phospholipids of vegetable oils are removed during the refining process. 

Pho.sphoinosiiides serve as storage forms for secondary messengers. Phosphoinositidc.s compose only a minor fraction (2-8 f) of the lipids in cell membranes, yet they can be converted to at least three intracellular messenger molecules arachidonic acid, inositol 1.4,5-ua.sphosphale (IP i). and 1.2-diacylglyeerol (DAG). The functions of arachidonic acid derivatives are discus.sed in Chapter 24. IP releases intracellular calcium, and DAG is an essential cofuctor in the activation of protein kina.se C." ... 

Cell-regulating polyunsaturated fatty acids primarily synthesized from arachidonic acid and released by the action of phospholipase A2 from lipids in cell membranes. 

T ecithin, one of the principal lipids in cell membranes, controls many important biological processes. Nevertheless, little is known about the structure of its films (1, 2, 3, 4). Electron micrographs now show remarkable properties for the thin film or monolayer of dipalmitoyl lecithin transferred quantitatively from a water surface. In many respects the water corresponds to the aqueous phases that bound cell membranes. 

The water insolubility of Cers, combined with strong intermolecular interactions, account for their participation in the water barrier of skin, where Cers are about one-third of the total lipid. In cell membranes, Cers tend to associate with rafts and caveolae and can affect membrane curvature. These may be important contributors to bilayer organization during cell signaling, for example, when SM is hydrolyzed to Cer in response to agonist activation of SMase [18]. Cer is also involved in cell signaling (as discussed in Section 5), and under certain conditions, Cers can form channels and induce leakiness in membranes, such as mitochondria, which may contribute to the induction of apoptosis (L.R. Montes, 2002 L.J. Siskind, 2006). 

The isoeicosanoids, a family of eicosanoid isomers, are formed nonenzymatically by direct free radical-based attack on AA and related lipid substrates. Unlike eicosanoids, these compounds are generated initially on the esterified lipid in cell membranes, from which they are cleaned, presumably by phospholipases the free isoeicosanoids circulate and are excreted in urine. Consequently, their production is not blocked in vivo by agents that suppress metabolism of free arachidonate, such as inhibitors of COX-1 or COX-2. Since several isoprostanes can activate prostanoid receptors, it has been speculated that they may contribute to the pathophysiology of inflammatory responses in a manner insensitive to COX inhibitors. 

After a discussion of types of reactions that can damage biological molecules such as lipids in cell membranes, this. section illustrates the ways antioxidant molecules such as vitamin E inhibit these proce.sses. The,se antioxidants share one property in common with 1.4-bcnzenediols They are easily oxidized, although they usually iircn t oxidized to quinones (their structures don t usually permit that). Read carefully to find out about. some molecules that arc gootl for you ... 

Inhalation anesthetics do not appear to work through a receptor mechanism and the mechanism of action remains a mystery. Theories suggesting that anesthetics work by altering the lipids in cell membranes stem from the observation that the potency of anesthetics correlates extremely closely with the solubility of the drug in oil. 

Triglycerides are the most abundant lipids in animals. They form depot fat, and hydrolysis of the ester bonds releases fatty acids and glycerol from adipose tissue. Phospholipids are the main stmctnral lipids in cell membranes, while glycoglycerolipids exist in cell membranes they are much less abimdant. 

Thermophiles and extreme thermophUes have characteristic membrane and enzyme systems that allow them to function at temperatures that would otherwise inhibit cellular transport and metaboUc activity. These adaptations include high proportions of saturated lipids in cell membranes to prevent melting, enzyme... 

At Stanford, Harden M. McConnell developed a new technique, called spin labelling, based upon EPR spectroscopy. While carbon-centered free radicals are extremely reactive and short-lived, radical oxides of nitrogen, such as NO and NO2, are moderately stable. McConnell noted that nitroxyl radicals (RR N-O) are extremely stable if R and R are tertiary and can be chemically attached to biological molecules of interest. In 1965, he published the concept of spin labeling and, in 1966, demonstrated that a spin-labelled substrate added to a-chymotrypsin forms a covalent enzyme-substrate complex. The EPR signal was quite broad suggesting restricted motion consistent with Koshland s induced-fit model. In 1971, McConnell published a smdy in which spin labelling indicated flip-flop motions of lipids in cell membranes. This was the start of dynamic smdies of cell membranes. 

Johansson, B. (2006) ToF-SlMS imaging of lipids in cell membranes. Surf. Interface Anal., 38,1401-1412. 

From these results, the hydrophobic interaction between proteins and lipids in cell membranes needs a farther insight in its understanding, while in a more general overview these approaches could have applications in a wide variety of processes where the adhesion of polypeptides has to be controlled (Figure 19). 

Both propanedial and the a, S-nnsatnrated aldehydes are extremely toxic, because they are highly reactive toward the proteins that are present in close proximity to the lipids in cell membranes. For example, both dials and enals are capable of reacting with nucleophilic amino and mercapto groups from two different parts of one protein or from two different protein molecules, and these reactions produce cross-linking (Section 14-10). Cross-linking severely inhibits proteins from carrying out their biological functions (Chapter 26). 

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