Receptor phospholipids

During the interaction between drug and phospholipid molecules, one or several of these parameters can change in a manner characteristic of both the drug and the receptor phospholipid membrane. 

In an extensive SFA study of protein receptor-ligand interactions, Leckband and co-workers [114] showed the importance of electrostatic, dispersion, steric, and hydrophobic forces in mediating the strong streptavidin-biotin interaction. Israelachvili and co-workers [66, 115] have measured the Hamaker constant for the dispersion interaction between phospholipid bilayers and find A = 7.5 1.5 X 10 erg in water. 

Brent et al., 1989] Brent, G. A., Dunn, M. K., Harney, J. W., Gulick, T., and Larsen, P. R. Thyroid hormone aporeceptor represses Ta inducible promoters and blocks activity of the retinoic acid receptor. New Biol. 1 (1989) 329-336 [Cevc and Marsh, 1987] Cevc, G., and Marsh, D. Phospholipid Bilayers Physical Principles and Models. John Wiley Sons, New York, 1987. 

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

Florio, V. A., and Stemweis, P. C. (1989). Mechanism of muscarinic receptor action on G0 in reconstituted phospholipid vesicles. J. Biol. Chem. 264 3909-3915. 

Akt is activated by binding of plasma membrane phospholipids downstream of insulin receptors, growth and survival factor receptors in a phosphoinositide 3-kinases dependent manner. In humans, there are three genes in the Akt family Aktl, Akt2 and Akt3. Their respective fimctions are still under investigation. 

Phospholipid Insulin Receptor Tyrosin Kinases Growth Factors... 

Caveolae are invaginations of the plasma membrane. They contain the protein caveolin and are rich in certain phospholipids. Similar to coated pits, they bud off internally forming endocytic vesicles. Caveolae play an important role in the internalization of certain cell surface receptors. 

Potential signaling phospholipid derived from phosphatidylcholine by phospholipase action. No receptors known. 

Signaling phospholipid derived from sphingomyelin by phospholipase action. Activates SIP receptors. 

FIGURE 6-15 Schematic representation of the ion permeability modulation for cation-responsive voltammetric sensors based on negatively charged lipid membranes. Complexation of the guest cation to the phospholipid receptors causes an increase of the permeability for the anionic marker ion. (Reproduced with permission from reference 49.)... 

Figure 25-3. Metabolic fate of chylomicrons. (A, apolipoprotein A B-48, apolipoprotein B-48 , apolipoprotein C E, apolipoprotein E HDL, high-density lipoprotein TG, triacylgiycerol C, cholesterol and cholesteryl ester P, phospholipid HL, hepatic lipase LRP, LDL receptor-reiated protein.) Only the predominant lipids are shown.

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

Angiotensin II binds to specific adrenal cortex glomerulosa cell receptors. The hormone-receptor interaction does not activate adenylyl cyclase, and cAMP does not appear to mediate the action of this hormone. The actions of angiotensin II, which are to stimulate the conversion of cholesterol to pregnenolone and of corticosterone to 18-hydroxycorticosterone and aldosterone, may involve changes in the concentration of intracellular calcium and of phospholipid metabolites by mechanisms similar to those described in Chapter 43. 

Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. 

Lipoproteins. A lipoprotein is an endogenous macromolecule consisting of an inner apolar core of cholesteryl esters and triglycerides surrounded by a monolayer of phospholipid embedded with cholesterol and apoproteins. The functions of lipoproteins are to transport lipids and to mediate lipid metabolism. There are four main types of lipoproteins (classified based on their flotation rates in salt solutions) chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). These differ in size, molecular weight, and density and have different lipid, protein, and apoprotein compositions (Table 11). The apoproteins are important determinants in the metabolism of lipoproteins—they serve as ligands for lipoprotein receptors and as mediators in lipoproteins interconversion by enzymes. 

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). 

Ryeom, SW, Silverstein, RL, Scotto, A, and Sparrow, JR, 1996a. Binding of anionic phospholipids to retinal pigment epithelium may be mediated by the scavenger receptor CD36. J Biol Chem 271, 20536-20539. 

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