Phospholipid in membranes

Browning, J. L. (1981). NMR studies of the structural and motional properties of phospholipids in membranes, in Liposomes From Physical Structure to Therapeutic Applications (C. G. Knight, ed.), Elsevier, Amsterdam, pp. 189-242. 

Cholesterol is found in many biological membrane and is the main sterol of animal organisms. It is eqnimolar with phospholipids in membranes of liver cell, erythrocytes, and myelin, whereas in human stratum comeum it lies in the outermost layer of the epidermis... 

Ohvo-Rekila, H., Ramstedt, B., Leppimaki, P. and Slotte, J. P. (2002). Cholesterol interactions with phospholipids in membranes, Progr. Lipid Res., 41, 66-97. 

Within a cell, a nncleotidase catalyses the hydrolysis of either a ribonncleotide or deoxyribonucleotide (Fignre 10.8). The qnantitatively important pathway for degradation of AMP in liver and mnscle involves deamination to IMP, catalysed by AMP deaminase, producing ammonia, and snbseqnent hydrolysis of IMP to inosine. This may be an important sonrce of inosine for synthesis of phosphati-dylinositol, a key phospholipid in membranes. 

Consequently any of the above factors or conditions could result in failure to produce sufficient amounts of these polyunsaturated fatty acids, which could result in modification of the type of fatty acids present in phospholipids in membranes, and hence the structure of the membranes. 

Comparison between DNA repair and phospholipid repair The processes that can lead to DNA damage and the type of damage are described in Chapter 9 and Appendix 9.6. The repair processes involve removal of the specific nucleotide(s) by an exonuclease and replacement of the nucleotide by a DNA polymerase. Since the strand must be broken to remove the damage (by an endonuclease) these parts of the strand must be repaired by a ligase. The process is known as excision-repair. Of interest, there is a degree of similarity between the removal of damaged polyunsaturated fatty acids from phospholipids in membranes and replacement with a new fatty acid by two enzymes, a deacylase and an acyltransferase (see above and Chapter 11), and excision-repair of DNA. 

Figure 20.18 The central dogma of molecular biology a summary of processes involved inflow of genetic information from DNA to protein. The diagram is a summary of the biochemical processes involved in the flow of genetic information from DNA to protein via RNA intermediates. This concept had to be revised following the discovery of the enzyme, reverse transcriptase, which catalyses information transfer from RNA to DNA (see Chapter 18). It may have to be modified in the future since changes in the fatty acid composition of phospholipids in membranes can modily the properties of proteins, and possibly their functions, independent of the genetic information within the amino acid sequence of the protein (See Chapters 7, 11 and 14).

Phosphatidylcholine (lecithin) is the most abundant phospholipid in membranes. Phosphatidylethanolamine (cephalin) has an ethanolamine residue instead of choline, and phosphatidylserine has a serine residue. In phosphatidylinositol, phosphatidate is esterified with the sugarlike cyclic polyalcohol myo-inositol. A doubly phosphorylated derivative of this phospholipid, phosphatidylinositol 4,5-bisphosphate, is a special component of membranes, which, by enzymatic cleavage, can give rise to two second messengers, diacylglycerol (DAG) and inositol l,4,5trisphosphate (InsPsi see p.386). 

The main action of vitamin E in human tissue is to prevent oxidation of polyunsaturated fatty acids (PUFA), thereby protecting lipid and phospholipids in membranes. Vitamin E interacts syn-ergically with other nutrients, such as vitamin C, selenium, and zinc, which are also involved in the oxidation pathway. The recommended intake is strongly related to the quantity of PUFA consumption. Some studies [454-456] on animal models and epidemiological trials in human suggest... 

Considering the different composition of phospholipids in membranes, it would be expected that the distribution of drugs into tissues and their localization therein would differ, and that the partition coefficients in membranes, log PM, would deviate in size and ranking from those determined in bulk octanol-water. Log PM can be strongly affected by the presence of charged head groups in the phospholipids, especially in the case of amphiphihc dmgs. 

IP3 is classified now as a second messenger with considerable influence on calcium movement from intracellular stores in a cell. Furthermore, diglycerides have a considerable and important effect on protein kinase C activity and location (Nishizuka, 1992). This is a classic example of an inactive (precursor) molecule being converted to a biologically active product. This reaction is an excellent example of the role of phospholipids in membrane processes through an enzyme-catalyzed reaction. 

Many of the phospholipids in membranes are glycerol derivatives that have two esterified fatty acids plus a charged side chain joined by a phosphate ester linkage. A typical example is phosphatidylcholine (lecithin), a major component of most membranes ... 

Seehg J. P Nuclear magnetic resonance and the head group structure of phospholipids in membranes. Biochim. Biophys. Acta 1978 515 105-140. 

The resultant modified E residues are gamma-carboxyglutamate (gla). This process is most clearly understood for factor II, also called preprothrombin. Prothrombin is modified pre-prothrombin. The gla residues are effective calcium ion chelators. Upon chelation of calcium, prothrombin interacts with phospholipids in membranes and is proteolysed to thrombin through the action of activated factor X (Xa). Dining the carboxylation reaction reduced hydroquinone form of vitamin K is converted to a 2,3-epoxide form. The regeneration of the hydroquinone form requires an uncharacterized reductase. This latter reaction is the site of action of the dicumarol-based anticoagulants such as warfarin. 

The nature of the fatty adds in the TGs stored in adipose tissue and those in the phospholipids in membranes can be influenced by the diet, The rat study reported in Table 6.3 assessed the plasma membranes of the liver. Diets containing 10% oil or fat by weight were fed to young and rapidly growing rats. Rapidly growing... 

Roberts, M. F., Bothner-By, A. A., and Dennis, E. A. (1978). Magnetic nonequivalence within the fatty acyl chains of phospholipids in membrane models H nuclear magnetic resonance studies of the a-methylene groups. Biochemistry 17,935—942. 

For example, flip-flop transfer of phospholipids in membranes is usually also very slow, from hours to days. However, there are exceptions for example, phosphatidylethanol undergoes rapid and reversible transbilayer distribution in unilamellar PC vesicles in the presence of multivalent cations, including calcium. ... 

How the asymmetric distribution of phospholipids in membrane leaflets arises is still unclear. In pure bilayers, phospholipids do not spontaneously migrate, or flip-flop, from one leaflet to the other. Energetically, such flip-flopping is extremely unfavorable because it entails movement of the polar phospholipid head group through the hydrophobic interior of the membrane. To a first approximation, the asym-... 

The usual asymmetric distribution of phospholipids In membrane leaflets Is broken down as cells (e.g., red blood cells) become senescent or undergo apoptosis. For Instance, phosphatidylserine and phosphatidylethanolamlne are preferentially located In the cytosolic leaflet of cellular membranes. Increased exposure of these anionic phospholipids on the exoplasmic face of the plasma membrane appears to serve as a signal for scavenger cells to remove and destroy old or d dng cells. Annexin V, a protein that specifically binds to anionic phospholipids, can be fluorescently labeled and used to detect apoptotic cells In cultured cells and In tissues. 

Flip-flopping between leaflets, lateral diffusion, and membrane fusion and fission are not the only dynamic processes of phospholipids In membranes. Their fatty acyl chains and. In some cases, their head groups are subject to ongoing covalent remodeling (e.g., hydrolysis of fatty esters by phospholipases and resynthesIs by acyl transferases). Another key... 

Fig. 33.28. Synthesis of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. The multiple pathways reflect the importance of phospholipids in membrane structure. For example, phosphatidylcholine (PC) can be synthesized from dietary choline when it is available. If choline is not available, PC can be made from dietary carbohydrate, although the amount synthesized is inadequate to prevent choline deficiency. SAM is S-adenosyhnethionine, a methyl group donor for many biochemical reactions (see Chapter 40).

The protein-sorbing properties characteristic of HDS impart preparations on its basis the ability to fix microorganisms. The interaction between silica and microorganisms is not distinguished for any specific nature. It is attributed to the affinity of silica particles to glycoproteid structures and to phospholipids in membranes of microbe cells. 

It should not be assumed that hydroxy fatty acids are biologically inactive. Hydroxy fatty acids are chemotactic and vasoactive. Such fatty acids could perturb phospholipids in membranes. For instance, cardiolipin containing hydroxy-linoleic acid does not support the electron transport coupled to ATP production of the mitochondrion. 5-Hydroxy de-canoic acid is a well-known inhibitor of the K -ATP channel. Isoprostanes, trihydroxy oxidation products of arachi-donic acid, are vasoconstrictors (76). 13-Hydroxy linoleic acid (13-HODE) is a lipoxygenase-derived metabolite that influences the thromboresistant properties of endothelial cells in culture (77). However, there is some doubt about the tme nature of these hydroxy-fatty acids generated by the cells, as there are several GSH- and NADPH-dependent pathways that can immediately reduce hydroperoxy- to hydroxy-fatty acids. Furthermore, the reduction step of the analytical method would have converted the hydroperoxy- to a hydroxy-group. Nevertheless, much work remains to be done to determine the relative contribution of hydroperoxy- and hydroxy- to the biological effects of fried fat, and in particular their role in endothelial dysfunction and activation of factor VII. There have been earlier suggestions that a diet rich in lipid peroxidation products may lead to atherosclerosis and CHD (34,78). 

Due to its fundamental role as alkyl donor, adenosylmethionine largely contributes to the post-synthetic alteration of macromolecules, both the informational (proteins and nucleic acids) and the non-informational ones (polysaccarides, and complex phospholipids in membrane assembly). For extensive discussion concerning the enzymology and the role of polysaccaride alteration by adenosylmethionine we refer to a review by Ballou. As far as phospholipids and proteins are concerned we refer to other papers of this Symposium (see Mozzi and Porcellati, and Paik and Galletti, respectively). 

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